60,542, 840 filed 10th February 2004, which is hereby incorporated by reference in its entirety. All patent and non-patent references cited in the application, or in the pre- sent application, are also hereby incorporated by reference in their entirety.

Field of invention The present invention relates to methods for the evaluation of the ability of a com- pound to interfere with a bacterial toxin-antitoxin complex and the bioactive species identifiable using said evaluation methods. The present invention also relates to pharmaceutical formulations and methods for treating an individual suffering from a disease, such as caused by a microbial cell. The present invention further relates to the use of one or more said bioactive species for the preparation of a medicament for the treatment of an individual in need thereof, such as an individual diagnosed with, or at risk of contracting, a bacterial disease. The present invention further re- lates to hygienic compositions capable of reducing or eliminating microbial cells, non-therapeutic methods for eliminating or reducing microbial cells, and methods for treating a plant diagnosed with, or at risk of developing, a disease caused by a mi- crobial cell.

Background of invention There are many instances in which elimination or reduction of bacteria may be de- sirable. One example is in preventing spoilage of food or other perishable items.

Reduction of bacterial numbers is also desirable within many environments, such as within the home or workplace, laboratories, food preparation areas, medical envi- ronments (including hospitals and medical equipment, such as catheters) and any other areas where bacteria could have a detrimental effect. Bacterial pathogens are also responsible for a plethora of human and animal diseases, ranging in severity from inapparent to severe, and elimination or reduction of these pathogenic bacteria is also highly desirable.

Bacterial disease Bacterial disease may be caused by bacterial infection, defined as the invasion of the host by microorganisms, which then multiply in close association with the host's tissues.

The capacity of a bacterium to cause disease reflects its relative pathogenicity. On this basis, bacteria can be organized into three major groups. When isolated from a patient, frank or primary pathogens are considered to be probable agents of dis- ease. Opportunistic pathogens are those isolated from patients whose host defense mechanisms have been compromised. They may be the agents of disease (e. g. , in patients who have been predisposed to urinary tract infections with Escherichia coli by catheterization). Finally, some bacteria are considered to be nonpathogens, be- cause they rarely or never cause human disease. Their categorization as nonpatho- gens may change, however, because of the adaptability of bacteria and the detri- mental effect of modern radiation therapy, chemotherapy, and immunotherapy on resistance mechanisms. In fact, some bacteria previously considered to be non- pathogens are now known to cause disease. Serratia marcescens, for example, is a common soil bacterium that causes pneumonia, urinary tract infections, and bac- teremia in immunocompromised hosts.

Virulence is the measure of the pathogenicity of an organism. The degree of viru- lence is related directly to the ability of the organism to cause disease despite host resistance mechanisms; it is affected by numerous variables such as the number of infecting bacteria, route of entry into the body, specific and nonspecific host defense mechanisms, and virulence factors of the bacterium. Virulence can be measured experimentally by determining the number of bacteria required to cause animal death, illness, or lesions in a defined period after the bacteria are administered by a designated route. Consequently, calculations of a lethal dose affecting 50 percent of a population of animals (LD50) or an effective dose causing a disease symptom in 50 percent of a population of animals (ED5o) are useful in comparing the relative viru- lence of different bacteria.

Bacterial virulence factors can influence a bacteria's ability to cause infectious dis- ease. These virulence factors can be divided into two categories: 1. virulence factors that promote bacterial colonization of the host

2. virulence factors that damage the host.

Bacterial virulence factors may be encoded on chromosomal, plasmid, transposon, or temperate bacteriophage DNA; virulence factor genes on transposons or temper- ate bacteriophage DNA may integrate into the bacterial chromosome.

Susceptibility to bacterial disease depends on the physiologic and immunologic condition of the host, the bacterial virulence and the number of bacteria that enter the body. Before increased amounts of specific antibodies or T cells are formed in response to invading bacterial pathogens, the"nonspecific"mechanisms of host resistance (such as polymorphonuclear neutrophils and macrophage clearance) must defend the host against the microbial cells. Development of effective specific immunity (such as an antibody response to the bacterium) may require several weeks. The normal bacterial flora of the skin and mucosal surfaces also serves to protect the host against colonization by bacterial pathogens. In most healthy indi- viduals, bacteria from the normal flora that occasionally penetrate the body (e. g., during tooth extraction or routine brushing of teeth) are cleared by the host's cellular and humoral mechanisms. In contrast, individuals with defective immune responses are prone to frequent, recurrent infections with even the least virulent bacteria. The best-known example of such susceptibility is acquired immune deficiency syndrome (AIDS), in which the CD4+ helper lymphocytes are progressively decimated by hu- man immunodeficiency virus (HIV). However, resistance mechanisms can be altered by many other processes. For example, aging often weakens both nonspecific and specific defense systems so that they can no longer effectively combat the chal- lenge of bacteria from the environment. Infants are also especially susceptible to certain pathogens (such as group B streptococci) because their immune systems are not yet fully developed and cannot mount a protective immune response to im- portant bacterial antigens. In addition, some individuals have genetic defects of the complement system or cellular defenses (e. g. , inability of polymorphonuclear neu- trophils to kill bacteria). Finally, a patient may develop granulocytopenia as a result of a predisposing disease, such as cancer, or immunosuppressive chemotherapy for organ transplants or cancer.

Host resistance can be compromised by trauma and by some underlying diseases.

An individual becomes susceptible to infection with a variety of bacteria if the skin or

mucosa is breached, particularly in the case of severe wounds such as burns or contaminated surgical wounds. Cystic fibrosis patients, who have poor ciliary func- tion and consequently cannot clear mucus efficiently from the respiratory tract, are abnormally susceptible to infection, particularly from mucoid strains of Pseudomo- nas aeruginosa, resulting in serious respiratory distress. Ascending urinary tract infections with Escherichia coli are common in women and are particularly trouble- some in patients with urinary tract obstructions. A variety of routine medical proce- dures, such as trachea intubation and catheterization of blood vessels and the ure- thra, increase the risk of bacterial infection. The plastic devices used in these proce- dures are readily colonized by bacteria from the skin, which migrate along the out- side of the tube to infect deeper tissues or enter the bloodstream.

Bacteria can be transmitted to the host via a number of modes of transmission.

Transmission may be direct, so from an infected host directly to a susceptible host, for instance via airborne transmission, direct contact transmission (via blood, ex- crement blood transfusions, organ transplants) or sexual transmission. Bacterial disease transmission may also be indirect, such as from infected host to reservoir to susceptible host, in which case the reservoir can be living (such as an arthropod vector or disease-free individual) or inanimate, for example soil, water, food, bed- ding or surgical instruments.

In certain bacterial diseases, tissue damage results from the host's own immune system. This is termed"host-mediated pathogenesis". Thus, the pathogenesis of many bacterial infections cannot be separated from the host immune response, for much of the tissue damage is caused by the host response rather than by bacterial factors. Classic examples of host-mediated pathogenesis are seen in diseases such as Gram-negative bacterial sepsis, tuberculosis, and tuberculoid leprosy. The tissue damage in these infections is caused by toxic factors released from the lympho- cytes, macrophages, and polymorphonuclear neutrophils infiltrating the site of infec- tion. Often the host response is so intense that host tissues are destroyed, allowing resistant bacteria to proliferate. In lepromatous leprosy, in contrast, the absence of a cellular response to Mycobacterium leprae allows the bacteria to multiply to such large numbers in the skin that they become tightly packed and replace healthy tis- sue.

Most bacterial pathogens do not invade cells, proliferating instead in the extracellu- lar environment enriched by body fluids. Some of these bacteria (e. g. , V cholerae and Bordetella pertussis) do not even penetrate body tissues, but, rather, adhere to epithelial surfaces and cause disease by secreting potent protein toxins. Although bacteria such as E coli and P aeruginosa are termed noninvasive, they frequently spread rapidly to various tissues once they gain access to the body.

Emerging infections Emerging infections are those whose incidence in humans has increased within the past two decades or threatens to increase in the near future. Emergence may be due to the spread of a new agent, to the recognition of an infection that has been present in the population but has gone undetected, or to the realization that an es- tablished disease has an infectious origin. Emergence may also be used to describe the reappearance (or"reemergence") of a known infection after a decline in inci- dence. "The 1995 Report of the Committee on International Science, Engineering and Technology Policy (a White House-appointed committee of the National Sci- ence and Technology Council to review the US role in dealing with emerging dis- eases) listed several pathogenic bacteria and bacterial diseases that have emerged since 1973, such as Legionnaires'disease (Legionella pneumophila), Bacteria Toxic shock syndrome (toxic strains of Staphylococcus aureus), Bacteria Hemorrhagic colitis and hemolytic uremic syndrome (Escherichia coli 0157 : H7), Lyme disease (Borrelia burgdorferi), peptic ulcer disease (Helicobacter pylori), Human ehrlichiosis (Ehrlichia chafeensis), a new epidemic cholera strain (Vibrio cholerae 0139), Bacte- ria Cat-saatch disease (Bartonella henselae) and bacillaryangiomatosis.

The continuing problem of newly identified emerging infections places a high strain on current microbial therapies.

Bioterrorism There is concern that bacterial disease may be brought about by warfare and/or terrorist activities. Certainly, some known bacteria, such as bacteria of the Bacillus genus, may be used for bioterrorist activities. One disease causing much concern is anthrax. While an anthrax vaccine is available (See e. g., Ivins et al., Vaccine 13: 1779 [1995] ) and can be used for the prevention of classic anthrax, genetic mixing of different strains of the organism can render the vaccine ineffective (See

e. g., Mobley, Military Med. 160: 547 [1995] ). The potential consequences of the use of Anthrax spores as a biological weapon were demonstrated by the accidental release of Bacillus anthracis from a military microbiology laboratory in the former Soviet Union. Seventy-seven cases of human anthrax, including 66 deaths, were attributed to the accident. Some anthrax infections occurred as far as 4 kilometers from the laboratory (See e. g., Meselson et al., Science 266: 1202 [1994] ). Genetic analysis of infected victims revealed the presence of either multiple strains or a genetically altered B. anthracis (See e. g. , Jackson et al., Proc. Nat. Acad. of Sci.

U. S. A. 95: 1224 [1998] ). There is thus a clear need for improved treatments and prevention of anthrax.

Current bacterial disease therapies Current bacterial disease therapies include, but are not restricted to: Cell wall synthesis inhibitors, such as: a. Beta-lactams (such as penicillin or cephalosporins), which block cell wall crosslinking by mimicking d-ala-d-ala b. Vancomycin, which binds d-ala-d-ala motifs.

Protein synthesis inhibitors, such as: a. Aminoglycosides (such as streptomycin), which are protein synthesis inhibi- tors that bind to the bacterial ribosome 30S subunit and cause misreading of the genetic code. b. Tetracyclines, which act on the bacterial ribosome 30S subunit and inhibit tRNA binding. c. Macrolides (such erythromycin) act on the bacterial ribosome 50S subunit, blocking peptidyl transfer. d. Oxazolidinones, which are active only against gram positive bacteria, and in- terfere with translation.

Nucleic acid metabolism inhibitors, such as: a. Sulfonamides, which are structural analogues of PABA and prevent formation of folic acid. The bacteria cannot import folic acid to make DNA bases. b. Trimethoprim, which inhibits dihydrofolic reductase and acts synergistically

with sulfonamides. c. Rifamycins, which block transcription by binding to RNA polymerase.

DNA gyrase inhibitors, such as: a. Quinolones, which inhibit DNA gyrase. New fluorinated derivatives (i. e. ciproflaxin) have a broad spectrum and are very potent. b. Novobiocin, which blocks binding of ATP to DNA gyrase.

Antimicrobial agents are most effective, however, when the infection is also being fought by healthy phagocytic and immune defenses. Some reasons for this situation are the poor diffusion of antibiotics into certain sites (such as the prostate gland), the ability of many bacteria to multiply or survive inside cells (where many antimicrobial agents have little or no effect), the bacteriostatic rather than bactericidal action of some drugs, and the capacity of some organisms to develop resistance to multiple antibiotics. This problem is now becoming very common, for instance recent surveys in Europe have shown that betwen 15 and 50 % of clinical isolates of S. pneumo- niae are resistant to penicillin.

An organism infected with an antibiotic-resistant strain of bacteria faces serious and potentially life-threatening consequences. Examples of bacteria that develop antibiotic resistance include Staphylococcus (often causing fatal infections), Pneumococci (causing for example pneumonia and meningitis); Salmonella and E. coli (causing for example diarrhea) and Enterococci (causing for example blood- stream, surgical wound and urinary tract infections). (See e. g., Berkelman et. al., J.

Infcet. Dis. 170 (2): 272 [1994]).

Bacterial toxin-antitoxin systems The bacterial toxin-antitoxin systems (TA systems) are encoded by bacterial plas- mids and chromosomes, which specify a cytotoxin and an antitoxin. The antitoxins neutralise the cognate toxins by forming tight complexes with them. The anti-toxins are unstable due to degradation by cellular proteases, whereas the toxins are sta- ble. TA loci usually comprise two genes in a transcriptional unit. One of the genes codes for the antitoxin which combines with and neutralizes the toxin, which is en- coded by the other gene. The antitoxins bind extremely well to their cognate toxins, both in vivo and in vitro, but do not bind to non-cognate toxins, that is, the interaction

between a toxin and the corresponding antitoxin is specific. The toxins are very po- tent cell killers or inhibitors of bacterial cell growth.

A number of these TA systems have been discovered (Gerdes, K,"Toxin-Antitoxin Modules May Regulate Synthesis of Macromolecules during Nutritional Stress", Journal of Bacteriology, Vol. 182, No. 3, p 561-572), including the following families: relBE systems (relB antitoxin, relE toxin) parDE systems chp systems (chpA locus has also been called mazEF) higBA systems (HigB toxin, HigA antitoxin) phd/doc systems ccdAB systems (ccdA antitoxin, ccdB toxin) vapBC systems (also known as vagCD or STBORF1 and STBORF2) The mode of action of these complexes has also been investigated; see for example Pedersen, K. et al., 2003. The Bacterial toxin RelE displays codon-specific cleavage of mRNAs in the ribosomal A-site. Cell 112,131-140 ; Christensen S. and Gerdes K.

2003. RelE proteins from Bacteria and Archaea inhibit protein synthesis by cleavage of translating mRNAs and is counteracted by tmRNA. Mol. Microbiol. 48: 1389-400; Christensen S, et al.,"Toxin-antitoxin Loci as Stress-response elements : ChpAK/MazF and ChpBK cleave translated RNAs and are counteracted by tmRNA", J. Mol. Biol. Volume 332, Issue 4,26 September 2003, Pages 809-819.

Although it has been suggested that, in theory, these systems could be used as novel anti-microbial targets with medical applications, there are many practical diffi- culties to be overcome to make this idea viable. Problems to be overcome include : 1) The anti-microbial would have to be targeted to the bacterial site 2) The anti-microbial would have to be taken up by the bacteria in a way that al- lowed it to remain in a viable, active form.

3) The anti-microbial would have to be targeted to the complex 4) The anti-microbial should be in a format allowing it to be toxic or detrimental to the microbial cell, but should not be toxic or detrimental to the cells of the indi- vidual thus treated.

5) The anti-microbial should not be eliminated from the body fluids or otherwise rendered inactive in the anti-microbial method used.

Furthermore, bacterial toxins such as RelE have been characterised as inducing apoptosis in human cells (Yamamoto et al.,"Bacterial toxin RelE induces apoptosis in human cells", FEBS Letters 519 p 191-194), so there is much uncertainty as to whether using TA complexes as drug targets could lead to detrimental cell death or retardation of growth in the individual thus treated. It is probable that this (possibly therapeutical problematic) wide-spectrum ability of the toxins to induce cell death is due to conserved elements of the translation machinery.

References Berry LJ: Bacterial toxins. Crit Rev Toxicol 5: 239,1977 Eisenstein TK, Actor P, Friedman H: Host Defenses to Intracellular Pathogens. Ple- num Publishing Co, New York, 1983 Finlay BB, Falkow S: Common themes in microbial pathogenicity. Microbiol Rev 53: 210,1989 Foster TJ: Plasmid-determined resistance to antimicrobial drugs and toxic metal ions in bacteria. Microbiol Rev 47 : 361,1983 Hardegree MC, Tu AT (eds): Handbook of Natural Toxins. Vol. 4: Bacterial Toxins.

Marcel Dekker, New York, 1988 Iglewski BH, Clark VL (eds): Molecular Basis of Bacterial Pathogenesis. Vol. Xi of Luderitz O, Galanos C: Endotoxins of gram-negative bacteria. p. 307. In Dorner F, Drews J (eds): Pharmacology of Bacterial Toxins. International Encyclopedia of Pharmacology and Therapeutics, Section 119. Pergamon, Elmsford, NY, 1986 Mims CA: The Pathogenesis of Infectious Disease. Academic Press, London, 1976 Payne SM: Iron and virulence in the family Enterobacteriaceae. Crit Rev Microbiol 16: 81,1988 Salyers, AA, Whitt DD: Bacterial Pathogenesis-A Molecular Approach ASM Press, 1994 Smith H, Turner JJ (eds): The Molecular Basis of Pathogenicity. Verlag Chemie, Deerfield Beach, FL, 1980 Summary of invention Clearly, antipathogenic compositions and methods that decrease the infectivity, morbidity, and mortality associated with bacterial pathogenic exposure are needed.

Such compositions and methods should preferably not have the undesirable properties of promoting microbial resistance, or of being toxic to the recipient.

The inventors of the present invention have advantageously found, after sustained bioinformatics investigations, that homologues to the TA systems mentioned above appear to be widespread among prokaryotes. It was found that many prokaryotes contain multiple copies of TA loci, increasing the importance of these complexes as drug targets.

Thus, in one aspect of the present invention is provided pharmaceutical formulations and methods for treating an individual suffering from a disease, such as caused by a microbial cell. The present invention further relates to the use of one or more said bioactive species for the preparation of a medicament for the treatment of an indi- vidual in need thereof, such as an individual diagnosed with, or at risk of contracting, a bacterial disease.

The present invention also relates to methods for the evaluation of the ability of a compound to interfere with a bacterial toxin-antitoxin complex and the bioactive spe- cies identifiable using said evaluation methods. Furthermore, the present invention relates to hygienic compositions capable of reducing or eliminating microbial cells, non-therapeutic methods for eliminating or reducing microbial cells, and methods for treating a plant diagnosed with, or at risk of developing, a disease caused by a mi- crobial cell.

In said methods, the bioactive species is targeted correctly to the bacterial site in a way that allows the bioactive species to remain in a viable, active form. The bioac- tive species are toxic or detrimental to the microbial cell (s) of interest, but are not toxic or detrimental to the cells of the individual thus treated.

Definitions Amino acid: Entity comprising an amino terminal part (NH2) and a carboxy terminal part (COOH) separated by a central part comprising a carbon atom, or a chain of carbon atoms, comprising at least one side chain or functional group. NH2 refers to the amino group present at the amino terminal end of an amino acid or peptide, and COOH refers to the carboxy group present at the carboxy terminal end of an amino

acid or peptide. The generic term amino acid comprises both natural and non- natural amino acids. Natural amino acids of standard nomenclature as listed in J.

Biol. Chem. , 243: 3552-59 (1969) and adopted in 37 C. F. R. , section 1.822 (b) (2) be- long to the group of amino acids listed in Table 1 herein below. Non-natural amino acids are those not listed in Table 1. Examples of non-natural amino acids are those listed e. g. in 37 C. F. R. section 1.822 (b) (4), all of which are incorporated herein by reference. Further examples of non-natural amino acids are listed herein below.

Amino acid residues described herein can be in the"D"or or"L"isomeric form.

Symbols Amino acid 1-Letter 3-Letter Y Tyr tyrosine G Gly glycine F Phe phenylalanine M Met methionine A Ala alanine S Ser serine I Ile isoleucine L Leu leucine T Thr threonine V Val valine P Pro proline K Lys lysine H His histidine Q Gln glutamine E Glu glutamic acid W Trp tryptophan R Arg arginine D Asp aspartic acid N Asn asparagine C Cys cysteine Table 1. Natural amino acids and their respective codes.

Amino acid residue: the term"amino acid residue"is meant to encompass amino acids, either standard amino acids, non-standard amino acids or pseudo-amino ac- ids, which have been reacted with at least one other species, such as 2, for example 3, such as more than 3 other species. In particular amino acid residues may com- prise an acyl bond in place of a free carboxyl group and/or an amine-bond and/or amide bond in place of a free amine group. Furthermore, reacted amino acids resi- dues may comprise an ester or thioester bond in place of an amide bond "binding"and"bound"-In preferred embodiments of the present invention,"binding" between e. g. the bound toxin and anti-toxin refers to contact between the two enti- ties with a dissociation constant of Kd less than 5 X 10-6M, such as less than 10-6M, e. g. less than 5 X 10-7M, such as less than 10-7M, e. g. less than 5 X 10-8M, such as less than 10-8M, e. g. less than 5 X 10-9M, such as less than 10-9M, e. g. less than 5 X 10-'°M, such as less than 10-'°M, e. g. less than 5 X 10-11M, such as less than 10- "M, e. g. less than 5 X 10-12M, such as less than 10-12M. Dissociation constants can e. g. be determined by surface plasmon resonance analysis.

"caused by"-by a disease"caused by"a microbial cell is meant that said disease may be associated with or directly caused by the bacteria, for example by a toxin, tissue damage, or host-mediated pathogensis.

By carrying out another therapy or treatment"in combination"with the methods of the present invention, it is meant that the methods of the present invention may be carried out before, during, or after another therapy or treatment type.

For example, if said another therapy comprises administering an anti-microbial compound, said anti-microbial compound may administered before, concurrently with, or after, the methods described herein. Said anti-microbial compounds may also be formulated in the medicaments described herein.

Infant-by"infant"is meant any individual of physical or apparent age from 0-3 years, said individual being preferably human.

Neonate-by"neonate"is meant any individual at the age from birth to one year old, said individual being preferably human.

Immunocompromised-by"immunocompromised"individual is meant herein an individual whose immune system is not functioning as well as in a normal healthy adult individual. In extreme examples, this may be due to diseases or medical treatments or other changes in the individual's body reducing the individual's im- mune function, such as AIDS, HIV, malnutrition, old age (defined herein as an indi- vidual over 50 years old, preferably over 70 years old), pregnancy, lactation, immu- nosuppressive drugs like steroids, chemotherapy, viruses (such as HIV, infectious bursal disease virus, cytomegalovirus), autoimmune disease, radiation, radiother- apy, sarcoidosis, leprosy, malaria, and the like. Furthermore, an individual is im- munocompromised if they have an underdeveloped immune system, for example due to a genetic disease or in the case of a foetus, infant, young child (from age 3 to 12) or adolescent (from age 13 to adult). In one form of immunosuppression, said individual has granulocytopenia. In another form of immunosuppression, said indi- vidual has trauma, burns, or a wound. Said wound may be a surgical wound.

Non-natural amino acid: Any amino acid not included in Table 1 herein above. Non- natural amino acids are capable of being incorporated into a peptide or peptide like structure by translation mediated by a ribosome. A non-natural amino acid according to the present invention may for example be any amino acid comprising an amino group and a carboxyl group separated by an a-carbon. The amino acid may for ex- ample be selected from the group consisting of, Aib, Nal, Sar, Orn, Lysine ana- logues DAP and DAPA or any of the amino acids described in US 5,573, 905. Fur- thermore, non-natural amino acids may be any of the above mentioned or any stan- dard amino acids which further comprises one or more moieties selected from the group consisting of hydroxyl, bromo, fluoro, chloro, iodo, mercapto, thio, cyano, al- kylthio, heterocycle, aryl, heteroaryl, carboxyl, carboalkoyl, alkyl, alkenyl, nitro, amino, alkoxyl and/or amido. The non-natural amino acid is capable of being incor- porated into a peptide or peptide like structure by translation mediated by a wild- type, mutant, modified or recombinant ribosome.

Peptide: Plurality of covalently linked amino acid residues defining a sequence and linked by amide bonds. The term is used analogously with oligopeptide and polypeptide. The amino acids may be both natural amino acids and non-natural amino acids, including any combination thereof. The natural and/or non-natural amino acids may be linked by peptide bonds or by non-peptide bonds. The term

peptide also embraces post-translational modifications introduced by chemical or enzyme-catalyzed reactions, as are known in the art. Such post-translational modifications can be introduced prior to partitioning, if desired. Amino acids as specified herein will preferentially be in the L-stereoisomeric form. Amino acid analogs can be employed instead of the 20 naturally-occurring amino acids. Several such analogs are known, including fluorophenylalanine, norleucine, azetidine-2- carboxylic acid, S-aminoethyl cysteine, 4-methyl tryptophan and the like.

Treatment-by"treatment"is meant for example prophylaxis, treatment or ameliora- tion of a disease, for example a bacterial infection. "Treating"an individual may thus comprise prevention, treatment, or amelioration of a disease. By"amelioration"is meant any improvement in the patient's health or quality of life, however small, i. e. the treatment may not necessarily lead to a disease cure.

Detailed description of the invention In one aspect of the present invention, a method is provided for treating an individual suffering from, or at risk of developing, a disease caused by a microbial cell, comprising at least one complex of a polypeptide toxin and an anti-toxin polypeptide and/or at least one polynucleotide encoding a polypeptide toxin and an anti-toxin polypeptide. Said method comprises the steps of i) contacting said microbial cell with a bioactive species capable of activating said polypeptide toxin and/or capable of initiating de novo synthesis of acti- vated polypeptide toxin, and/or capable of increasing the total amount of ac- tivated polypeptide toxin and ii) obtaining in said microbial cell an activated polypeptide toxin in an amount sufficient for achieving at least an impaired growth or elimination of said mi- crobial cell having caused said infection in said individual.

Said method preferably comprises the further step of providing a pharmaceutical composition, comprising at least one bioactive species. (By"further step"is meant herein that the step may occur at any point in the process, such as before step (i).) Said bioactive species is capable of contacting and activating in a microbial cell at

least one polypeptide toxin selected from the group of polypeptide toxins consisting of 'rye) RelE and variants thereof ParE and variants thereof Chp (or MazE) and variants thereof Hig and variants thereof Doc and variants thereof CcdB and variants thereof VapC and variants thereof Said polypeptide toxin optionally forms a complex with an anti-toxin polypeptide prior to activation, said complex being capable of reducing or inhibiting the toxic activity of the polypeptide toxin.

It is preferred that said step of contacting the microbial cell with the bioactive spe- cies is selected from a) contacting the cell surface of the microbial cell with the bioactive species, and/or b) uptake of the bioactive species in the microbial cell and contacting an in- tracellular component of the microbial cell with the bioactive species.

In another preferred embodiment of the present invention, said step of activation of the at least one polypeptide toxin results from one or more of a) de novo synthesis of activated polypeptide toxin, wherein the de novo synthesised and activated polypeptide toxin does not form a complex with an anti-toxin polypeptide, and/or b) dissociation of polypeptide toxin and anti-toxin polypeptide present in the same complex, wherein said dissociation results in the release from the complex of polypeptide toxin in an active form, or a form capable of being activated following dissociation from the anti-toxin polypeptide, and op- tionally

c) degradation of the anti-toxin Microbial cell Said microbial cell may be any microbe capable of causing any form of disease in at least one individual, including, but not restricted to: microbes of the genus Achromobacter, preferably Achromobacter xylosoxidans microbes of the genus Acinetobacter, preferably Acinetobacter calcoaceticus, microbes of the genus Actinomyces, preferably Actinomyces israelii, microbes of the genus Aeromonas, preferably Aeromonas hydrophila, microbes of the genus Alcaligenes, preferably selected from Alcaligenes faecalis, Alcaligenes odorans or Alcaligenes denitrificans, microbes of the genus Arizona, preferably Arizona hinshawii, microbes of the genus Bacillus, preferably selected from Bacillus anthracis, Bacillus subtilis, Bacillus cereus, Bacillus fragilis, microbes of the genus Bacteroides, preferably Bacteroides melaninogenicus, microbes of the genus Burkholderia, preferably Burkholderia pseudomallei or Burkholderia mallei, microbes of the genus Bordetella, preferably Bordetella pertussis, microbes of the genus Borrelia, preferably Borrelia burgdorferi or Borrelia recurrentis, microbes of the genus Brucella, preferably Brucella melitensis, Brucella abortus, Brucella suis or Brucella canis, microbes of the genus Calymmatobacterium or Calymmatobacterium granulomatis, microbes of the genus Campylobacter, preferably Campylobacter fetus, microbes of the genus Chrombacterium, preferably Chrombacterium violaceum, microbes of the genus Citrobacter, preferably selected from Clostridium difficile, Clostridium tetani, Clostridium botulinum or Clostridium perfringens, microbes of the genus Corynebacterium, preferably selected from Corynebacterium diphtheriae, Corynebacterium ulcerans, Corynebacterium haemolyticum or Corynebacterium pseudotuberculosis, microbes of the genus Coxiella, preferably Coxiella burnetti, microbes of the genus Cryptosporidium, preferably Cryptosporidium parvum, microbes of the genus Deinococcus, microbes of the genus Edwardsiella, preferably Edwardsiella tarda, microbes of the genus Eikenelfa, preferaby Eikenella corrodens, microbes of the genus Enterobacter, preferably selected from Enterobacter cloace, Enterobacter aerogenes, Enterobacter hafniae (Hafnia alvei) or Enterobacter ag- glomerans, microbes of the genus Erysipelothrix, preferably Erysipelothrix rrhu- siopathiae, microbes of the genus Escherichia, preferably selected from Escherichia

coli, Escherichia coli-enterotoxigenic (ETEC), Escherichia coli-enteropathogenic (EPEC), Escherichia coli 0157 : H7 enterohemorrhagic (EHEC), Escherichia coli- enteroinvasive (EIEC), or E. coli Enteroaggregative (EAggEC), microbes of the ge- nus Eubacterium, preferably Eubacterium alactolyticum, microbes of the genus Francisella, preferably Francisella tularensis, microbes of the genus Flavobacterium, preferably Flavobacterium meningosepticum; microbes of the genus Fusobacterium, preferably Fusobacterium nucleatum ; microbes of the genus Gardnerella, preferably Gardnerella vaginalis ; microbes of the genus Haemophilus, preferably selected from Haemophilus aegyptius or Hemophilus influenzae ; microbes of the genus Helico- bacter, preferably Helicobacter pylori ; microbes of the genus Intrasporangium, mi- crobes of the genus Janthinobacterium, microbes of the genus Klebsiella, prefera- bly selected from Klebsiella pneumoniae, Klebsiella ozaenae or Klebsiella rhinoscleromatis ; microbes of the genus Kingella, microbes of the genus Legionella, preferably Legionella pneumophilia ; microbes of the genus Leptospira, preferably Leptospira interrogans; microbes of the genus Listeria, preferably Listeria monocytogenes, microbes of the genus Glueonobacter, microbes of the genus Mo- biluncus ; microbes of the genus Mycobacterium, preferably selected from Mycobac- terium tuberculosis, Mycobacterium avium or Mycobacterium bovis, microbes of the genus Moraxella, preferably selected from Moraxella catarrhalis, Moraxella lacunata or Moraxella osloensis, microbes of the genus Neisseria, preferably selected from Neisseria gonorrhoeae or Neisseria meningitidis; microbes of the genus Nocardia, preferably selected from Nocardia asteroides or Nocardia brasiliensis ; microbes of the genus Oscillospira, microbes of the genus Peptococcus, preferably Peptococcus magnus; microbes of the genus Peptostreptococcus, microbes of the genus Plesio- monas, preferably Plesiomonas shigelloides, microbes of the genus Porphyromo- nas; microbes of the genus Proteus, preferably selected from Proteus mirabilis or Proteus vulgaris, microbes of the genus Prevotella ; microbes of the genus Provi- dencia, selected from Providencia alcalifaciens, Providencia stuartii, Providencia rettgeri ; microbes of the genus Pseudomonas, preferably selected from Pseudomo- nas aeruginosa, Pseudomonas mallei or Pseudomonas pseudomallei ; microbes of the genus Rickettsia, preferably selected from Rickettsia rickettsii or Rickettsia conorii; microbes of the genus Salmonella, preferably selected from Salmonella choleraesuis, Salmonella typhimurium, Salmonella typhi; microbes of the genus Ser- ratia, preferably Serratia marcescens; microbes of the genus Shigella, preferably selected from Shigella dysenteriae, Shigella sonnei/flexneri or Shigella boydii; mi-

crobes of the genus Spirillum, preferably Spirillum minor, microbes of the genus Staphylococcus, preferably selected from Staphylococcus aureus, Staphylococcus epidermidis or Staphylococcus aprophyticus; microbes of the genus Streptobacillus, preferably Streptobacillus moniliformis ; microbes of the genus Streptococcus, pref- erably Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus pyo- genes, Streptococcus pneumoniae, Streptococcus faecalis, Streptococcus faecium, Streptococcus durans, Streptococcus viridans or Streptococcus mutans ; Spirillum, preferably Spirillum minus; microbes of the genus Treponema, preferably selected from Treponema pallidum, Treponema carateum or Treponema pertenue; microbes of the genus Vibrio, preferably selected from Vibrio cholerae, Vibrio cholerae 01, Vibrio cholerae non-01, Vibrio parahaemolyticus or Vibrio vulnificus ; microbes of the genus Wolinella ; microbes of the genus Wolbachia ; microbes of the genus Xantho- monas, preferably Xanthomonas maltophilia ; microbes of the genus Yersinia, pref- erably selected from Yersinia pestis, Yersinia enterocolitica or Yersinia pseudotu- berculosis, or microbes of the genus Zoogloea.

In one preferred embodiment of the present invention, said microbe comprises a relBE TA system. Said microbe is preferably a gram negative bacteria, such as se- lected from one or more of Brucella melitensis, Brucella suis, Helicobacter pylori, Escherichia coli, Escherichia coli 0157, Shigella flexneri, Coxiella burnetii, Vibrio cholerae, Vibrio parahaemolyticus, Vibrio vulnificus, Haemophilus influenzae, Pseudomonas aeruginosa, Pseudomonas putida KT2440, Pseudomonas syrin- gae, Salmonella typhimurium and Salmonella typhi. In another preferred embodi- ment, said microbe is a gram positive bacteria, such as selected from Mycobacte- rium tuberculosis, Enterococcus faecalis, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus mutans, Streptococcus pneumonia, or Fusobacterium nucleatum.

In another preferred embodiment of the present invention, said microbe comprises a vapBC TA system. Said microbe is preferably a gram positive bacterium, such as Mycobacterium tuberculosis. Equally preferably, said microbe is a gram negative bacterium, such as on or more of Rickettsia conorii, Coxiella burnetii, Haemophilus influenzae, Pseudomonas syringae, Salmonella typhimurium, Salmonella typhi and Leptospira intrerrogans.

In another preferred embodiment of the present invention, said microbe comprises a mazEF TA system. Said microbe is preferably a gram positive bacterium, such as one or more of Mycobacterium tuberculosis, Bacillus anthracis, Bacillus cereus, Bacillus halodurans, Clostridium perfringens, Enterococcus faecalis, Listeria monocytogenes, Staphylococcus aureus, Staphylococcus epidermidis, Streptococ- cus mutans and Streptococcus pneumonia. Equally preferably, said bacterium is a gram negative bacterium, such as one or more of Brucella melitensis, Brucella suis, Rickettsia conorii, Neisseria meningitidis, Escherichia coli, Escherichia coli 0157, Shigella flexneri, Vibrio cholerae, Vibrio parahaemolyticus, Pseudomonas putida or Leptospira intrerrogans.

In another preferred embodiment of the present invention, said microbe comprises a parDE TA system. Said microbe preferably comprise a gram positive bacterium, such as one or more of Mycobacterium tuberculosis, Streptococcus agalactiae, or Streptococcus pyogenes. Equally preferably, said bacterium is a gram negative bacterium, such as one or more of Escherichia coli 0157, Escherichia coli, Coxiella burnetii, Vibrio cholerae, Vibrio parahaemolyticus, Vibrio vulnificus, Pseudomonas aeruginosa and Pseudomonas syringae.

In another preferred embodiment of the present invention, said microbe comprises a higBA TA system. Said microbe preferably comprises a gram negative bacterium, such as Neisseria meningitidis, Escherichia coli, Coxiella burnetii, Vibrio cholerae, Haemophilus influenzae, Pseudomonas aeruginosa, Pseudomonas putida KT2440 and Pseudomonas syringae.

In another preferred embodiment of the present invention, said microbe comprises a phd/doc TA system. Said microbe is preferably a gram positive bacterium, such as one or more of Clostridium tetani, Enterococcus faecalis and Streptococcus pneumonia. Equally preferably, said microbe is a gram negative bacterium, such as one or more of Brucella melitensis, Brucella suis, Neisseria meningitidis, Yersinia pestis, Vibrio cholerae, Pseudomonas aeruginosa, Salmonella typhimurium and Salmonella typhi.

In another preferred embodiment of the present invention, said microbe comprises a ccdAB TA system. Preferred microbes in this category include Escherichia coli or Escherichia coli 0157.

Individual Said individual may be any organism capable of suffering from, or at risk of develop- ing, a disease caused by a microbial cell, More preferably, said individual is an ani- mal, more preferably a vertebrate, most preferably a mammal. Said individual may be a domestic animal, such as a pet or farm animal, or may be a a wild animal. Most preferably, said individual is human. Said individual may be female, or, equally pref- erably, may be male. In one preferred embodiment of the present invention, said individual is pregnant or lactating. In another, equally preferred embodiment, said individual has undergone endotracheal intubation. In another, equally preferred em- bodiment, said individual has undergone bladder catheterization. In another, equally preferred embodiment, said individual has undergone central venous catheteriza- tion. In another, equally preferred embodiment, said individual has undergone peri- toneal dialysis. In another, equally preferred embodiment, said individual is immuno- compromised. In one preferred embodiment, said immunocompromised individual has been, is being, or will be treated with an immunosuppressive drug, for example one or more steroid. In another preferred embodiment, said individual is suffering from a disease not caused by a bacteria, such as an autoimmune disease, sarcoi- dosis, leprosy, cytomegalovirus infections, malaria, a parasitic disease, a fungal disease or a viral infection. Preferably, said viral infection is caused by one or more of HIV, infectious bursal disease virus or cytomegalovirus.

In another, equally preferred embodiment, said individual has HIV or AIDS. In an- other, equally preferred embodiment, said individual is a neonate. In another, equally preferred embodiment, said individual is an infant. Said individual may be from 0-130 years old, such as 0-3 years old, such as 3-6 years old, such as 6-10 years old, such as 10-20 years old, such as 20-30 years old, such as 40-50 years old, such as 50-60 years old, such as 60-70 years old, such as 70-80 years old, such as 70-130 years old.

Disease It is preferred that said disease is caused by any bacterium. Examples of suitable diseases capable of being treated by the methods of the present invention are listed below, together with descriptions of the diseases (where appropriate) and examples of bacteria associated with these diseases. (Other bacteria not disclosed herein capable of causing these, and other bacterial diseases, are also envisaged as falling

within the scope of the present invention; the bacteria referred to are merely examples of some of the causative bacteria for these diseases and do not serve to limit the invention in any way): Abscesses-Bacteroides fragilis, Eikenella corrodens # Acrodermatitis chronica atrophicans (ACA)-late skin manifestation of latent Lyme disease-Borrelia burgdorferi (Spirochetes) <BR> <BR> <BR> <BR> Actinomycosis-Actinomyces israelii<BR> <BR> <BR> <BR> <BR> <BR> Acute bacterial Prostatitis-E coli Anthrax (Black Bane, Malignant pustule, Wool sorter's disease or Tanner's disease) Bacillus anthracis Australian tick typhus (Australian Spotted Fever or Queensland Tick Typhus) Rickettsia australis Bang's disease (Brucellosis) Brucella sp.

Bartonellosis (Verruga peruana, Carrion's disease or Oroya fever) Bartonella bacilliformis, caused by sandfly bites at elevations of 600 to 2800 meter in Peru, Ecuador and Colombia.

"Black death" (plague)-Yersinia pestis Bacillary angiomatosis-Bartonella henselae Bacterial vaginosis-Bacteroides spp. , Gardnerella vaginalis, Mobiluncus spp.

Bejel (endemic syphilis) Treponema pallidum var. pallidum # Blepharitis - caused by infestation of the eyelash follicle by a mite, which re- sults in an allergic reaction leading to secondary infection with Staphylococ- cus aureus or Staphylococcus epidermidis.

Boils-Staphylcoccus aureus Botulism-Clostridium botulinum Boutonneuse fever (Fievre boutonneuse or Tick typhus)-Rickettsia conori Brazilian purpuric fever-Haemophilus aegyptius Bronchitis Brucellosis-Brucella sp.

Bullous impetigo-Staphylococcus aureus # Buruli ulcers (Mycoburuli ulcers)-Mycobacterium ulcerans Campylobacteriosis-Campylobacter sp.

Chromobacteriosis-Chromobacterium violaceum Cryptosporidiosis-Cryptosporidium parvum Carate (Mal del pinto or Pinta)-Treponema pallidum var. carateum <BR> Carditis<BR> <BR> <BR> Carbuncle-Staphylcoccus aureus 'Cat Scratch fever (Cat Scratch Disease)-Bartonella henselae Cholera-Vibrio cholerae Clap (Gonorrhea)-Neisseria gonorrhoeae Conjunctivitis (pink eye) (*)-Haemophilus aegyptius, # Cystitis or Pyelonephritis-Escherichia coli, Klebsiella sp, Enterobacter sp. , Serratia sp. , Proteus sp. , Providencia sp. , Morganella sp. , Pseudomonas aeruginosa, Staphylococcus saprophyticus, Enterococcus sp. , Staphylococ- cus aureus, Staphylococcus epidermidis, Streptococcus agalactiae # Dacryocytitis- Staphylococcus aureus, Staphylococcus epidermidis, Strepto- coccus pneumoniae Diphtheria-Corynebacterium diphtheriae Disseminated Intravascular Coagulation-most commonly Escherichia coli Donovanosis (Granuloma inguinale)-Calymmatobacterium granulomatis Ehrlichiosis-Ehrlichia sp., transmitted by ticks Endemic Relapsing fever-Borrelia sp.

# Endocarditis-Streptococcus of the viridans group, Staphylococcus aureus, Staphylococcus epidermidis Endophthalmitis-Staphylococcus aureus, Staphylococcus epidermidis, Bacil- lus cereus, Streptococcus pneumoniae, Streptococcus pyogenes.

# Enteric infections-Various Gram negative bacteria, such as Campylobacter fetus, Shigellasp., Escherichia coli, Salmonella sp. , Arizona hinshawii Epidemic Relapsing fever-Borrelia recurrentis Epiglottitis-Haemophilus influenzae Erysipeloid (Erysipelothricosis)-Erysipelothrix rhusiopathiae Erysipelis-Streptococcus pyogenes Erythema chronicum migrans-Borrelia burgdorferi Erythema marginatum-Streptococcus pyogenes Erythema multiforme-seen in coccidioidomycosis (Coccidioides immitis) Erythema nodosum-seen in coccidioidomycosis (Coccidioides immitis)

* Erythrasma-Corynebacterium minutissimum Fitz-Hugh-Curtis syndrome (Perihepatitis)-Neisseria gonorrhoeae * Flinders Island Spotted Fever-Rickettsia honei # Frambesia (Yaws) -Treponema pallidum var. pertenue Furunculosis (boil furuncle)-Staphylcoccus aureus Folliculitis-Staphylcoccus aureus * Gas gangrene-Clostridium perfringens Glanders-Burkholderia mallei (used to be named Pseudomonas mallei ; G- rod) <BR> <BR> <BR> <BR> # Granuloma inguinale (donovanosis) - Calymmatobacterium granulomatis Hamburger disease (Hemolytic Uremic Syndrome)-Escherichia coli 0157 H7 strain.

Hard chancre (syphilis)-Treponema pallidum subsp. pallidum Haverhill fever (Rat bite fever)-Streptobacillus moniliformis Helicobacterosis (duodenal ulcers)-He/icobacter pylori Hidradenitis-Staphylcoccus aureus Human monocytic ehrlichiosis-Ehrlichia chaffeensis, transmitted by ticks Human granulocytic ehrlichiosis-Ehrlichia equi, transmitted by ticks Impetigo-Streptococcus pyogenes, Staphylococcus aureus Inclusion conjunctivitis (Swimming Pool conjunctivitis or Pannus) Infantile diarrhea-Escherichia coli (ETEC-enterotoxigenic E. coli) Israeli spotted fever-unnamed Rickettsia Legionnaire's pneumonia-Legionella pneumophila <BR> <BR> <BR> <BR> Leptospirosis-Leptospira interrogans<BR> <BR> <BR> <BR> <BR> <BR> <BR> Listerosis-Listeria monocytogenes<BR> <BR> <BR> <BR> <BR> <BR> <BR> Lockjaw-Tetanus-Clostridium tetani Ludwig's angina-usually a polymicrobial infection (cellulitis of the floor of the mouth with spread to the submental, sublingual and submandibular spaces).

Caused by bacteria from mouth.

# Lyme disease - Borrelia burgdorferi Malta fever (Brucellosis)-Brucella sp.

# Mediterannean spotted fever-Rickettsia coronii Melioidosis (Whitmore's disease)-Burkholderia pseudomallei (used to be called Pseudomonas pseudomallel)

'Meningitis, (spotted fever) bacterial-Neisseria meningitidis, Haemophilus in- fluenzae, Listeria, Streptoccoccus pneumoniae, Group B streptococcus, Ed- wardsiella tarda Montezuma's Revenge (Traveler's diarrhea) -Any number of bacteria (Es- cherichia coli, Salmonella, Shigella, Yersinia, Vibrio, etc. ), that cause diar- rhea.

Multiple Organ Dysfunction Syndrome or MODS-many bacterial species.

Murine typhus-Rickettsia typhi Myositis-Streptococcus pyogenes, Staphylococcus aureus Myocarditis Necrotizing fasciitis-Streptococcus pyogenes, Staphylococcus aureus Nocardiosis (Nocardia) Nongonococcal urethritis-Gardnerella vaginalis Asian tick typhus-Rickettsia sibirica Nosocomial infections-a wide range of bacteria that may cause nosocomial infections, for example Achromobacterxylosoxidans, Acinetobacter cal- coaceticus Opthalmia neonatorium (Gonorrhea)-Neisseria gonorrhoeae Oriental Spotted Fever-Rickettsia japonica Otitis media-Streptococcus pneumoniae, Haemophilus influnezae, Morax- ella catarrhalis Otitis externa-Pseudomonas aeruginosa Osteomyelitis-Staphylococcus aureus, Streptococcus sp. , members of the enterobacteriaceae, Peptococcus magnus.

PCP pneumonia-Pneumonia caused by Pneumocystis carinii Peliosis hepatica-Bartonella henselae Pelvic Inflammatory Disease (PID)-Neiserria gonorrhoeae, anaerobic bacte- ria, Facultative Gram negative rods, Actinomyces israelii Pertussis (Whooping cough)-Bordetella pertussis Pigbel-beta-toxin of Clostridium perfringens type C Pinta-Treponema carateum Pitted Keratolysis-Micrococcus sedentarius Plague-Yersinia pestis

Pneumonia-Acinetobacter sp. , Actinomyces sp. , Bacillus anthracis, Bacter- oides melaninogenicus, Bordetella pertussis, Burkholderia pseudomallei, Burkholderia mallei, Coxiella burnetii (Q-fever), Escherichia coli, Francisella tularensis, Fusobacterium sp. , Hemophilus influenzae, Klebsiella pneumo- niae, Legionella pneumophila, Moraxella catarrhalis, Mycobacterium tubercu- losis, Mycobacterium sp. , Neisseria meningitidis, Nocardia sp. , Porphyromo- nas sp., Prevotella sp. , Proteus sp. , Pseudomonas aeruginosa, Serratia sp. , Serratia marcescens, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Staphylococcus aureus, Peptostreptococcus sp. , Yersinia pestis and other bacteria Pontiac fever-Legionella pneumophila Postanginal septicemia (Lemierre's Syndrome)-Fusobacterium necropho- rum Prostatitis, bacterial-Escherichia coli, Klebsiella sp. , Proteus sp. , Pseudo- <BR> <BR> <BR> <BR> monas sp., Enterobacter sp., Serratia sp., Enterococcus feacalis<BR> <BR> <BR> <BR> <BR> <BR> Pseudomembranous colitis-Clostridium difficile Puerperal fever-Streptococcus pyogenes Pylephlebitis-Bateroides fragilis, Peptostreptococcus, Clostridium spp, and several of the Enterobacteriaceae.

Pyelonephritis-E. coli Q fever-Coxiella burnetti Quinsy (Peritonsillar abscess) - (Streptococcus pyogenes) Rat bite fever-Spirillum minor, Streptobacillus moniliformis Reiter Syndrome-resulting from a nongonococcal sexually transmitted dis- ease due usually to an infectious diarrhea (Shigella, Salmonella, Yersinia).

Persons with an HLA-B27 major histocompatibility complex are more likely to get this disease.

Relapsing fever-Borrelia recurrentis # Rheumatic fever-Streptococcus pyogenes Rhinoscleroma-Klebsiella rhinoscleromatis Rickettsialpox-Rickettsia akari, contracted from mite bites 'Rocky Mountain spotted fever-Rickettsia rickettsii Salmonellosis-Salmonella spp.

Scarlet fever (Scarlatina)-Streptococcus group A (Streptococcus pyogenes)

Scalded Skin Syndrome-exfoliative toxin producing strains of Staphylococ- cus aureus Scrub typhus-Rickettsia tsutsugamushi (contracted e. g. by a chigger bite) Sennetsu fever (Ehrlichiosis) Ehrlichia sp. , transmitted by ticks Sepsis/Septic Shock-50% due to Gram negative bacteria; 50% due to Gram positive bacteria. Most common sites of infection leading to sepsis are lungs, abdomen, and urinary tract.

Septic arthritis-Neisseria gonorrhoeae, Staphylococcus aureus Shigellosis-Shigella sp Siberian tick typhus-Rickettsia sibirica Sinusitis-Streptococcus pneumoniae, Haemophilus influenzae Staphylococcal enterotoxin poisoning-Staphylococcus aureus Stie-Hordeola-Staphylococcus aureus Strep. throat-Streptococcus pyogenes Stomach ulcers-Helicobacter pylori Stomach cancer-Helicobacter pylori Systemic Inflammatory Response Syndrome or SIRS-many types of bacte- ria may be involved.

Tabes dorsalis (tertiary syphilis)-Treponema pallidum subsp. pallidum TB-Tuberculosis-Mycobacterium tuberculosis Tooth decay-bacteria such as Streptococcus mutans, Fusobacterium nu- cleatum 'Toxic Shock Syndrome-Staphylcoccus aureus (producing TSST) and Strep- tococcus pyogenes 'Trench fever (5-day fever)-Bartonella quintana Trench mouth or Vincent's disease-Various anaerobic bacteria in the mouth Trichomycosis axillaris-Corynebacterium tenuis Tuberculosis-Mycobacterium tuberculosis Tularemia-rabbit fever-deer fly fever-Francisella tularensis Typhoid fever-Salmonella typhi (G-rod: facultative-straight : enteric patho- gens) Typhus fever-Rickettsia typhi (flea-borne), Rickettsia conorii Urethritis-N. gonorrhoeae, C. trachomatis Undulant fever-Brucella sp.

Urethritis-Neisseria gonorrhoeae Vaginosis, bacterial-Peptostreptococccus sp. , Bacteriodes sp. , Gardnerella vaginalis, Mobiluncus sp.

Vaginitis Waterhouse-Friderichsen syndrome-Neisseria meningitidis Weil's diseases (Leptospirosis)-Leptospira interrogans Whipple's disease-Tropheryma whippelEi Yaws-Treponema pertenue Yersinosis-Yersinia enterocolitica In one preferred embodiment of the present invention, said disease is stomach cancer.

In another preferred embodiment of the present invention, said bacterial disease is a dental infection. Preferred bacterial diseases in this class include, but are not re- stricted to, tooth decay and periodontal disease, caused for example by excessive formation of organic acids which break down enamel of teeth.

In another preferred embodiment of the present invention, said bacterial disease affects the skin. Preferred bacterial diseases in this class include, but are not re- stricted to: Impetigo (Staphylococcus aureus, Streptococcus pyogenes), Folliculitis, boils (Staphylococcus aureus), Scalded Skin Syndrome (Staphylococcus aureus), Erysipelas (Streptococcus pyogenes), Lyme disease (Borrelia burgdorferi), Syphilis (Treponema pallidum), and Rocky Mountain Spotted Fever (Rickettsia rickettsil).

The causative bacteria mentioned herein are examples and should not be viewed as restricting the scope of the invention.

In another preferred embodiment of the present invention, said bacterial disease affects one or more of an individual's eyes. Preferred bacterial diseases in this class include, but are not restricted to: Pink Eye (conjunctivitis-Haemophilus aegyptius), and Opthalmia neonatorium (Neisseria gonorrhoeae). The causative bacteria men- tioned herein are examples and should not be viewed as restricting the scope of the invention.

In another preferred embodiment of the present invention, said bacterial disease is a disease of the gastrointestinal tract. Preferred bacterial diseases in this class include, but are not restricted to, noninflammatory gastroenteritis (caused by, for example, one or more of Staphylococcus aureus, Bacillus cereus, Clostridium perfringens, Clostridium botulinum, E. coli (EPEC), E. coli (ETEC), E. coli (EAggEC or enteroadherent EC), Vibrio cholerae and/or Clostridium difficile), inflammatory Gastroenteritis (caused by, for example, one or more of Vibrio cholerae, Enterotoxigenic (ETEC) E coli, Enteropathogenic (EPEC) E. coli, Enteroaggregative (EAggEC) E. coli, Clostridium difficile, Vibrio parahemolyticus, Bacillus anthracis, E. coli (EIEC), E. coli (EHEC), Salmonella typhimurium, Salmonella typhi, Shigella dysenteriae type 1, Shigella sonneilflexneri, Yersinia enterocolitica, or invasive gastroenteritis (caused by, for example, one or more of Shigella sp. , Salmonella sp. , Enteroinvasive E. coli (EIEC), Enterohemorrhagic E. coli (EHEC), Vibrio vulnificus, Yersinia sp. , Francisella tularensis, Helicobacter pylori.

Preferred microbes causing disease of the gastrointestinal tract include, but are not restricted to, Staphylococcus aureus, Bacillus cereus, Clostridium perfringens, Clostridium botulinum, E. coli (EPEC), E. coli (ETEC), E. coli (EAggEC or enteroadherent EC), Vibrio cholerae 01, Vibrio cholerae non-01, Enteropathogenic (EPEC) E. coli, Clostridium difficile, Vibrio parahemolyticus, Bacillus anthracis, E. coli (EIEC), E. coli (EHEC), Salmonella spp, Salmonella typhimurium, Salmonella typhi, Shigella dysenteriae type 1, Shigella sonnei/flexneri, Yersinia enterocolitica, Shigella sp. , Enteroinvasive E. coli (EIEC), Enterohemorrhagic E. coli (EHEC), Yersinia sp., Francisella tularensis, Helicobacter pylori, Staphylococcus aureus, Yersinia pseudotuberculosis, Listeria monocytogenes, Vibrio parahaemolyticus, Vibrio sp. , Vibrio vulnificus, Clostridium perfringens, Bacillus cereus, Aeromonas hydrophila, Plesiomonas shigelloides, Streptococcus sp., enterovirulent Escherichia coli group (EEC Group), Escherichia coli-enterotoxigenic (ETEC), Escherichia coli 0157: H7 enterohemorrhagic (EHEC) and Clostridium difficile In another preferred embodiment of the present invention, said disease is pneumonia, for example caused by one or more of the following bacteria: Acinetobacter sp., Actinomyces sp., Bacillus anthracis, Bacteroides melaninogeni- cus, Bordetella pertussis, Burkholderia pseudomallei, Burkholderia mallei, Coxiella

burnetii (Q-fever), Escherichia coli, Francisella tularensis, Fusobacterium sp. , He- mophilus influenzae, Klebsiella pneumoniae, Legionella pneumophila, Moraxella catarrhalis, Mycobacterium tuberculosis, Mycobacterium sp. , Neisseria meningitidis, Nocardia sp. , Porphyromonas sp., Prevotella sp. , Proteus sp. , Pseudomonas aeruginosa, Serratia sp. , Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Staphylococcus aureus, Peptostreptococcus sp. , and Yersinia pestis.

In another preferred embodiment of the present invention, said disease is a nosocomial infection. In one preferred embodiment of the present invention, said nosocomial infection is selected from a urinary tract infection, a surgical site infection, pneumonia and a systemic infection.

In another preferred embodiment of the present invention, said microbe is an oppor- tunistic bacterial pathogen, such as for example Staphylococcus aureus, E. coli, Stenotrophomonas (Xanthomonas) maltophilia, Salmonella sp. , Rhodococcus equi.

Shigella flexneri, Pseudomonas aeruginosa, Listonella anguillarum, Burkholderia cepacia or Mycobacterium, Nocardia asteroides, Nocardia brasiliensis, and Nocar- dia otitidiscaviarum.

In another preferred embodiment of the present invention, said microbe is resistant to one or more antibiotics, for example resistant strains of Staphylococcus sp. (such as MRSA-methicillin-resistant staph aureus), Pneumococcus sp., Salmonella sp. , E. coli, Enterococcus sp. , S. Pneumoniae, Enterococcus sp., Enterobacter sp., Klebsiella pneumoniae, Campylobacter sp, Listeria monocytogenes, Haemophilus influenzae, Bacillus subtilis, Streptococcus pneumoniae, Mycobacterium tuberculosis, E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Klebsiella oxytoca, Morganella morganii, Enterobacter agglomerans, Enterococcus faecalis, Enterococcus faeium and/or Staphylococcus epidermidis Modes of transmission The diseases treated by the present invention may be transmitted via any mode of transmission. In one preferred embodiment of the present invention, said mode of transmission is via airborn transmission, and preferred diseases in this class in- clude, but are not restricted to, diseases involving the respiratory system, diphtheria,

pneumonia, tuberculosis, Legionnaire's disease, skin diseases, impetigo, cellulitis, systemic diseases, rheumatic fever and menigititis.

In another preferred embodiment of the present invention, said mode of transmission is via arthropods, such as insects, such as ticks, mites, larvae, lice, fleas, flies, or gnats. Preferred bacterial diseases in this class include, but are not restricted to, typhoid fever, Lyme disease, rickettsial typus, erlichiosis, spotted- fever, Scrub Typhus (Tsutsugamushi disease), Rickettsia tsutsugamushi (caused by the bite of a larval mite), Rickettsia) pox (Rickettsia akari), Tularemia (Francisella tularensis), Rocky Mountain Spotted Fever Rickettsia rickettsia (cause by a tick bite), Endemic Relapsing Fever (Borrelia sp. , caused by a tick bite), Sennetsu fever (Ehrlichia canis, E sennetsu, E. chaffeensis, E. equi, E, phagocytophilia, caused by the bite of a tick), Trench fever (bacillary angiomatosis or bacillary peliosis, Bartonella quintana, caused by a louse bite contaminated by louse feces or crushing louse on skin), louse-borne relapsing fever or epidemic relapsing fever (Borrelia recurrentis, caused by louse bite contaminated by louse feces or crushing louse on skin), Plague (Yersina pestis, caused by a flea bite and/or flea faeces), Murine typhus (Rickettsia typhi, caused by flea bite and/or flea faeces, Tularemia (Francisella tularensis, caused by the bite of an infected fly, Bartonellosis (Oroya fever or Carrion's disease-Bartonella bacilliformis, caused by the bite of an infected fly), Tick-borne Relapsing Fever (Borrelia recurrentis), Tularemia (Francisella tularensis) or Cat Scratch Fever (Bartonella henselae, may be transmitted via a tick). The causative bacteria and vectors mentioned herein are examples and should, not be viewed as restricting the scope of the invention.

In another preferred embodiment of the present invention, said mode of transmis- sion is via direct contact of the bacteria with the individual's body, preferably via di- rect contact of the bacteria with the skin, mucous membranes or underlying tissues.

Preferred bacterial diseases in this class include, but are not restricted to, anthrax, cat-scratch fever, gas gangrene, leprosy, peptic ulcers, staphylococcal infections, syphilis, or systemic diseases such as staphylococcal diseases, gonorrhea, or teta- nus In another preferred embodiment of the present invention, said mode of transmis- sion is via ingestion of food or water, such as for example unpasteurised dairy prod-

ucts, leading for example to bacterial infection (the pathogen enters the gastrointes- tinal tract and multiplies) or intoxication due to ingestion of bacterial toxins. Preferred bacterial diseases in this class include, but are not restricted to, Campylobacteriosis (Campylobacter sp.), Salmonellosis (Salmonella sp. ), Hemolytic Uremic Syndrome (E. coli 0157: H7), Yersiniosis (Yersinsia enterocolitica), Listeriosis (Listeria monocy- togenes), Tuberculosis (Mycobacterium tuberculosis), Brucellosis (Brucella sp. ), Cryptosporidiosis (Cryptosporidium parvum), Staphylococcal enterotoxin poisoning (Staphylococcus aureus), Q fever (Coxiella burnetti), Campylobacter gastroenteritis, shigellosis, listeriosis, traveler's diarrhea, typhoid fever, botulism, cholera, and food poisoning, such as staphylococcal food poisoning. The causative bacteria men- tioned herein are examples and should not be viewed as restricting the scope of the invention. Preferred foo-borne disease-causing bacteria include Salmonella spp. , Clostridium botulinum, Staphylococcus aureus, Yersinia enterocolitica, Yersinia pseudotuberculosis, Listeria monocytogenes, Vibrio cholerae 01, Vibrio cholerae non-01, Vibrio parahaemolyticus and other vibrios, Vibrio vulnificus, Clostridium perfringens, Bacillus cereus, Aeromonas hydrophila and other spp. , Plesiomonas shigelloides, Shigella spp. , Miscellaneous enterics, Streptococcus, enterovirulent Escherichia coli group (EEC Group), Escherichia coli-enterotoxigenic (ETEC), Es- cherichia coli-enteropathogenic (EPEC), Escherichia coli 0157 : H7 enterohemor- rhagic (EHEC) or Escherichia coli-enteroinvasive (EIEC) In another preferred embodiment of the present invention, said mode of transmis- sion is via sexual transmission. Preferred bacterial diseases in this class include, but are not restricted to, Bacterial vaginosis (Bacteroides spp, Gardnerella vaginalis, Mobiluncus spp), enteric infections (various gram negative bacteria, Campylobacter fetus, Shigellasp., Escherichia coli, Salmonella sp. ), Gonorrhea (Neisseria gonor- rhoeae), Granuloma inguinale (donovanosis-Calymmatobacterium granulomatis), Group B streptococcal infections (Streptococcus agalactiae), NGU or Nongonococ- cal urethritis (Gardnerella vaginalis), Pelvic Inflammatory Disease (N. gonorrhoeae, Anaerobic bacteria, Facultative Gram negative rods, Actinomyces israelil) or Syphilis (Treponema pallidum). The causative bacteria mentioned herein are examples and should not be viewed as restricting the scope of the invention.

In one preferred embodiment of the present invention, a method of the present in- vention is used in combination with another medical treatment. In one preferred em-

bodiment, said medical treatment is organ transplant or organ transplant aftercare.

In another, equally preferred embodiment, said medical treatment is chemotherapy.

In another preferred embodiment, said another medical treatment is for treatment of one or more of: a neoplastic disease, cystic fibrosis, AIDS, HIV, a bacterial disease, pregnancy or birth complications. In another preferred embodiment of the present invention, said medical treatment causes or contributes to immunodeficiency or im- paired immune system function of the individual thus treated.

In another preferred embodiment of the present invention, a method of the present invention is used in combination with an anti-microbial treatment. Said anti-microbial treatment preferably comprises administration of at least one anti-microbial compound. In one preferred embodiment of the present invention, said anti- microbial compounds comprises one or more bacterial cell wall synthesis inhibitor, such as Vancomycin or a beta-lactam, for example penicillin and/or a cephalosporin. Equally preferably, said anti-microbial compound comprises one or protein synthesis inhibitor, such as an Aminoglycoside (streptomycin), a Tetracycline, Macrolide (erythromycin) and/or an Oxazolidinone. Equally preferably, said anti-microbial compound comprises one or more nucleic acid metabolism inhibitor, such as a Sulfonamide, Trimethoprim and/or a Rifamycin. Equally preferably, said anti-microbial compound comprises one or more DNA gyrase inhibitor, such as a Novobiocin, Quinolone, a Quinolone derivative or, more preferably, a fluorinated derivative of Quinolone. Equally preferably, said anti- microbial compounds comprises an ampicillin or carbapenem.

Complex of a polypeptide toxin and an anti-toxin polypeptide By"complex of a polypeptide toxin and an anti-toxin polypeptide"is meant a poly- peptide toxin bound to its cognate antitoxin polypeptide. Said polypeptide toxin is capable of causing a detrimental effect on said microbial cell, such as reduction in microbial cell growth, cellular dysfunction or cell death. Said anti-toxin polypeptide is capable of preventing or reducing the detrimental effect of the polypeptide toxin on the microbial cell, preferably by binding said toxin or otherwise preventing the mode of action of said toxin. Said complex is preferably a known TA complex, more pref- erably from one or more of the following TA complex families (the family members in each family being termed"variants"):

relBE systems parDE systems chp systems (also termed mazEF) higBA systems . phd/doc systems ccdAB systems vapBC systems (also known as vagCD or STBORF1 and STBORF2) By"cognate anti-toxin"is meant a particular anti-toxin capable of reducing or pre- venting the detrimental effect of the toxin in question.

Said toxin preferably comprises a sequence of 10-300 amino acids, such as 20-250 amino acids, such as 30-200 amino acids, such as 40-175 amino acids, such as 50- 160 amino acids, for example 55-140 amino acids, such as 60-100 amino acids, such as 70-90 amino acids. In one preferred embodiment of the present invention, said polypeptide toxin is from the RelE toxin family, such as a polypeptide toxin comprising a sequence selected from, or substantially identical to SEQ ID NO : 2,4, 6,8, 10,12, 14, and 16. Said polypeptide toxin from the RelE family may in another preferred embodiment have a sequence comprising a sequence with at least 80 % sequence identity to one or more of SEQ ID NO : 2,4, 6, 8, 10,12, 14, and 16, such as at least 85 % sequence identity, such as at least 90 % sequence identity, such as at least 95 % sequence identity, such at least 99 % sequence identity. In another preferred embodiment of the present invention, said polypeptide toxin from the RelE family comprises a sequence, characterised in that said sequence produces an E value of 104 or less when compared to one or more of SEQ ID NO : 2,4, 6,8, 10, 12,14, and 16 using the BLAST algorithm version (2.04) set to the default parame- ters defined herein, such as an E value of 10-5 or less, such as an E value of 10-10 or less, such as a polypeptide toxin comprising a sequence selected from SEQ ID NO : 17-97. In another preferred embodiment, said toxin is any of the toxins with se- quences as given in Example 5.

In one preferred embodiment of the present invention, said polypeptide toxin is from the VapC toxin family, such as a polypeptide toxin comprising a sequence selected from, or substantially identical to, SEQ ID NO : 99,101, 103 and 105. In another pre-

ferred embodiment of the present invention, said polypeptide toxin of the VapC fam- ily comprises a sequence with at least 80 % sequence identity to one or more of SEQ ID NO : 99,101, 103 and 105, such as at least 85 % sequence identity, such as at least 90 % sequence identity, such as at least 95 % sequence identity, such as at least 99 % sequence identity. In another preferred embodiment of the present inven- tion, said polypeptide toxin of the VapC toxin family comprises a sequence, charac- terised in that said sequence produces an E value of 10-5 or less when compared to one or more of SEQ ID NO : 99,101, 103 and 105 using the BLAST algorithm version (2.04) set to the default parameters defined herein, such as an E value of 104, such as an E value of 10-'° or less, such as a polypeptide with sequence comprising a sequence selected from SEQ ID NO : 106-154.

In another preferred embodiment of the present invention, said polypeptide toxin is from the MazF toxin family, such as said polypeptide has a sequence comprising a sequence selected from or substantially identical to SEQ ID NO : 155 and 160. In another preferred embodiment of the present invention, said polypeptide toxin from the MazF family comprises a sequence with at least 80 % sequence identity to one or more of SEQ ID NO : 155 and 160, such as at least 85 % sequence identity, such as at least 90 % sequence identity, such as at least 95 % sequence identity, such as at least 99 % sequence identity. In another preferred embodiment of the present invention, said polypeptide toxin from the MazF family comprises a sequence, char- acterised in that said sequence produces an E value of 104 or less when compared to one or more of SEQ ID NO : 155 and 160 using the BLAST algorithm version (2.04) set to the default parameters defined herein, such as an E value of 10-5 or less, such as an E value of 10-10 or less, such as a polypeptide toxin comprising a sequence selected from SEQ ID NO : 161-205.

In another preferred embodiment of the present invention, said polypeptide toxin is from the ParE toxin family, such as a polypeptide toxin comprising a sequence with, or substantially identical to, SEQ ID NO : 207. In another preferred embodiment of the present invention, said polypeptide toxin from the ParE family comprises a se- quence with at least 80 % sequence identity to SEQ ID NO : 207, such as at least 85 % sequence identity, such as at least 90 % sequence identity, such as at least 95 % sequence identity, such as at least 99 % sequence identity. In another preferred embodiment of the present invention, said polypeptide toxin of the ParE family com-

prises a sequence, characterised in that said sequence produces an E value of 104 or less when compared to SEQ ID NO : 207 using the BLAST algorithm version (2.04) set to the default parameters defined herein, such as an E value of 10-5 or less, such as an E value of 10-1° or less, for example said polypeptide toxin com- prises a sequence selected from SEQ ID N0 : 208-219.

In another preferreed embodiment of the present invention, said polypeptide toxin is from the HigB toxin family, for example said polypeptide toxin from the HigB toxin family comprises a sequence with SEQ ID NO : 221, or a substantially identical vari- atn thereof. In another preferred embodiment of the present invention, said polype- tide toxin comprises a sequence with at least 80 % sequence identity to one or more of SEQ ID NO : 221, such as at least 85% sequence identity, such as at least 90 % sequence identity, such as at least 95% sequence identity, such as at least 99 % sequence identity. In another preferred embodiment of the present invention, said polypeptide toxin of the HigB toxin family comprises a sequence, characterised in that said sequence produces an E value of 104 or less when compared to one or more of SEQ ID NO : 221 using the BLAST algorithm version (2.04) set to the default parameters defined herein, such as an E value of 10-5 or less, such as an E value of 10-1°, for example said polypeptide toxin of the HigB toxin family comprises a se- quence selected from SEQ ID N0 : 222-240.

In another preferred embodiment of the present invention, said polypeptide toxin is from the Doc toxin family, such as a polypeptide comprising the sequence SEQ ID NO: 242 or a sequence substantially identical thereto. In another preferred embodi- ment of the present invention, said polypeptide toxin from the Doc toxin family com- prises a sequence with at least 80 % sequence identity to one or more of SEQ ID NO: 242, such as at least 85 % sequence identity, such as at least 90 % sequence identity, such as at least 95 % sequence identity, such as at least 99 % sequence identity. In another preferred embodiment of the present invention, said polypeptide toxin of the Doc family comprises a sequence, characterised in that said sequence produces an E value of 104 or less when compared to one or more of SEQ ID NO : 242 using the BLAST algorithm version (2.04) set to the default parameters defined herein, such as an E value of 10-5 or less, such as an E value of 10-10 or less, for example said polypeptide toxin comprises a sequence selected from SEQ ID NO : 243-257.

In another preferred embodiment of the present invention, said polypeptide toxin is from the CcdB toxin family, such as a polypeptide comprising the sequence SEQ ID NO: 259, or a sequence substantially identical thereto. In another preferred em- bodiment of the present invention, said polypeptide toxin of the CcdB toxin family comprises a sequence with at least 80 % sequence identity to one or more of SEQ ID NO: 259, such as at least 85 % sequence identity, such as at least 90 % se- quence identity, such as at least 95 % sequence identity, such as at least 99 % se- quence identity. In another preferred embodiment of the present invention, said polypeptide toxin of the CcdB toxin family comprises a sequence, characterised in that said sequence produces an E value of 104 or less when compared to one or more of SEQ ID NO: 259 using the BLAST algorithm version (2.04) set to the default parameters defined herein, such as an E value of 10-5 or less, such as an E value of 10-1° or less, for example a sequence comprising a sequence selected from SEQ ID NO : 260-263.

In another preferred embodiment of the present invention, said polypeptide toxin comprises a sequence, evaluated as a"final hit"using the following iterative BLAST protocol for evaluating sequences: a) Compare the query sequence of any of SEQ ID NO: 2,4, 6,8, 10,12, 14,16, 99,101, 103,105, 155,160, 207,221, 242 or 259 with the se- quences to be evaluated, using the BLAST algorithm version (2.04) set to the de- fault parameters defined herein. Collect all"hit"sequences characterised by gener- ating an E value of 104 or less. b) Repeat step a), but using the"hit"sequences as query sequences this time, again comparing these new query sequences with the sequences to be evaluated. c) Repeat step b) at least once, until no further"hit"sequences are found. d) Use the"hit"sequences found in the previous steps as query sequences to com- pare with any of SEQ ID : 17-97,106-154, 161-205,208-219, 222-240, 243-257 and 260-263 using the the BLAST algorithm version (2.04) set to the default parameters defined herein."Final hit"sequences are characterised by generating an E value of 10 or less.

The"sequences to be evaluated"are preferably in a genome or polypeptide se- quence database.

It is preferred that said polypeptide antitoxin is the cognate antitoxin to any of the toxins listed above, such as any of the antitoxins listed in Example 5.

In another preferred embodiment of the present invention, said polypeptide antitoxin is from the RelB family, such as said polypeptide antitoxin comprises a sequence selected from, or substantially identical to, SEQ ID NO: 1,3, 5,7, 9, 11, 13 and 15. In another preferred embodiment of the present invention, said polypeptide antitoxin from the RelB family comprises a sequence with at least 80 % sequence identity to one or more of SEQ ID : 1,3, 5,7, 9, 11, 13 and 15, such as at least 85 % sequence identity, such as at least 90 % sequence identity, such as at least 95 % sequence identity, such as at least 99 % sequence identity to one or more of SEQ ID NO: 1,3, 5,7, 9, 11, 13 and 15. In another preferred embodiment of the present invention, said polypeptide antitoxin comprises a sequence, characterised in that said se- quence produces an E value of zu or less when compared to one or more of SEQ ID NO: 1,3, 5,7, 9, 11, 13 and 15, using the BLAST algorithm version (2.04) set to the default parameters defined herein, such as an E value of 10-5 or less, such as an E value of 10-10 or less.

In another preferred embodiment of the present invention, said polypeptide antitoxin is from the VapB family, such as said antitoxin comprises a sequence selected from, or substantially identical to, SEQ ID NO: 98,100, 102 and 104. In another pre- ferred embodiment of the present invention, said polypeptide antitoxin of the VapB family comprises a sequence with at least 80 % sequence identity to one or more of SEQ ID : 98,100, 102 and 104, such as at least 85 % sequence identity, such as at least 90 % sequence identity, such as at least 95 % sequence identity, such as at least 99 % sequence identity. In another preferred embodiment of the present inven- tion, said polypeptide antitoxin of the VapB family comprises a sequence, character- ised in that said sequence produces an E value of 10 or less when compared to one or more of SEQ ID NO: 98,100, 102 and 104, using the BLAST algorithm ver- sion (2.04) set to the default parameters defined herein, such as an E value of 10-5, such as an E value of 1 O-10.

In another preferred embodiment of the present invention, said polypeptide antitoxin is from the MazE family, such as said antitoxin comprises a sequence selected from, or substantially identical to SEQ ID NO: 156,157, 158 and 159. In another preferred embodiment of the present invention, said polypeptide antitoxin of the MazE family comprises a sequence with at least 80 % sequence identity to one or more of SEQ ID : 156,157, 158 and 159, such as at least 85 % sequence identity, such as at least 90 % sequence identity, such as at least 95 % sequence identity, such as at least 99 % sequence identity. In another preferred embodiment of the present invention, said polypeptide antitoxin comprises a sequence, characterised in that said sequence produces an E value of 10-4 or less when compared to one or more of SEQ ID NO: 156,157, 158 and 159, using the BLAST algorithm version (2.04) set to the default parameters defined herein, such as an E value of 10-5 or less, such as an E value of 10-1° or less.

In another preferred embodiment of the present invention, said polypeptide antitoxin is from the ParD family, for example said polypeptide antitoxin comprises a se- quence with SEQ ID NO: 206, or a substantially identical sequence thereof. In an- other preferred embodiment of the present invention, said polypeptide antitoxin of teh ParD family comprises a sequence with at least 80 % sequence identity to SEQ ID : 206, such as at least 85 % sequence identity, such as at least 90 % sequence identity, such as at least 95 % sequence identity, such as at least 99 % sequence identity. In another preferred embodiment of the present invention, said polypeptide antitoxin of the ParD family comprises a sequence, characterised in that said se- quence produces an E value of 10-4 or less when compared to SEQ ID NO: 206, using the BLAST algorithm version (2.04) set to the default parameters defined herein, such as an E value of 10-5 or less, such as an E value of 10-10 or less.

In another preferred embodiment of the present invention, said polypeptide antitoxin is from the HigA family, such as a polypeptide antitoxin comprises a sequence with SEQ ID NO: 220 or a sequence substantially identical thereof. In another preferred embodiment of the present invention, said polypeptide antitoxin of the HigA family comprises a sequence with at least 80 % sequence identity to SEQ ID : 220, such as at least 85 % sequence identity, such as at least 90 % sequence identity, such as at least 95 % sequence identity, such as at least 99 % sequence identity. In another preferred embodiment of the present invention, said polypeptide antitoxin of the

HigA family comprises a sequence, characterised in that said sequence produces an E value of 104 or less when compared to SEQ ID NO: 220, using the BLAST algorithm version (2.04) set to the default parameters defined herein, such as an E value of 10-5 or less, such as an E value of 10-10 or less.

In another preferred embodiment of the present invention, said polypeptide antitoxin is from the Phd family, such as said polypeptide antitoxin comprises a sequence with SEQ ID NO: 241, or a substantially identical sequence thereto. In another pre- ferred embodiment of the present invention, said polypeptide antitoxin of the Phd family comprises a sequence with at least 80 % sequence identity to SEQ ID: 241, such as at least 85 % sequence identity, such as at least 90 % sequence identity, such as at least 95 % sequence identity, such as at least 99 % sequence identity. In another preferred embodiment of the present invention, said polypeptide antitoxin comprises a sequence, characterised in that said sequence produces an E value of 104 or less when compared to SEQ ID NO: 241, using the BLAST algorithm version (2.04) set to the default parameters defined herein, such as an E value of 10-5 or less, such as an E value of 10-1° or less.

In another preferred embodiment of the present invention, said polypeptide antitoxin is from the CcdA family, such as said polypeptide antitoxin comprises a sequence selected from SEQ ID NO: 258, or a substantially identical sequence thereto. In an- other preferred embodiment of the present invention, said polypeptide antitoxin of the CcdA family comprises a sequence with at least 80 % sequence identity to SEQ ID : 258, such as at least 85 % sequence identity, such as at least 90 % sequence identity, such as at least 95 % sequence identity, such as at least 99 % sequence identity. In another preferred embodiment of the present invention, said polypeptide antitoxin comprises a sequence, characterised in that said sequence produces an E value of 104 or less when compared to SEQ ID NO: 258, using the BLAST algo- rithm version (2.04) set to the default parameters defined herein, such as an E value of 10-5 or less, such as an E value of 10-l'or less.

In another preferred embodiment of the present invention, said anti-toxin polype- tide is the cognate anti-toxin to any of the toxin polypeptides described herein, in- cluding an toxin capable of being evaluated as a"final hit"in the iterative BLAST protocol described above.

At least one polvnucleotide encoding a polVpeptide toxin and an antitoxin polype- tide By"at least one polynucleotide encoding a polypeptide toxin and an antitoxin poly- peptide"is meant herein that said microbial cell comprises: (i) at least one polynucleotide encoding a polypeptide toxin, preferably com- prised on a longer polynucleotide stretch, such as a bacterial plasmid or chromosome.

(ii) At least one polynucleotide encoding a polypeptide antitoxin, preferably comprised on a longer polynucleotide, such as a bacterial plasmid or chro- mosome. More preferably, the gene coding for said toxin is closely spatially linked to the gene for its cognate anti-toxin, such as within 500 bp, such as within 450 bp, such as within 400 bp, such as within 350 bp, such as within 300 bp, such as within 250 bp, such as within 200 bp, such as within 100 bp, such as within 90 bp, such as within 73 bp, such as within 60 bp, such as within 50 bp, such as within 40 bp, such as within 30 bp, such as within 20 bp. In another preferred embodiment, said polynucleotide encoding a anti- toxin is between 10-300 codons long, such as 15-250 codons long, such as 20-200 codons long, such as 25-175 codons long, such as 42-140 codons long, for example 60-90 codons long.

In the methods described herein, it is preferred that said said polynucleotide encod- ing a polypeptide toxin encodes any of the polypeptide toxins described herein and/or that said polynucleotide encoding a polypeptide antitoxin encodes any of the polypeptide antitoxins described herein.

As used herein, "sequence identity"or"identity"in the context of two nucleic acid or polypeptide sequences includes reference to the residues in the two sequences which are the same when aligned for maximum correspondence over a specified comparison window. When percentage of sequence identity is used in reference to proteins it is recognized that residue positions which are not identical often differ by conservative amino acid substitutions, where amino acid residues are substituted for other amino acid residues with similar chemical properties (e. g. charge or hydro- phobicity) and therefore do not change the functional properties of the molecule.

Where sequences differ in conservative substitutions, the percent sequence identity may be adjusted upwards to correct for the conservative nature of the substitution.

Means for making this adjustment are well-known to those of skill in the art. Typi- cally this involves scoring a conservative substitution as a partial rather than a fall mismatch, thereby increasing the percentage sequence identity. Thus, for example, where an identical amino acid is given a score of 1 and a non-conservative substitu- tion is given a score of zero, a conservative substitution is given a score between zero and 1. The scoring of conservative substitutions is calculated, e. g. , according to the algorithm of Meyers and Miller, Computer Applic. Biol. Sci. , 4: 11-17 (1988) e. g., as implemented in the program PC/GENE (Intelligenetics, Mountain View, Calif., USA).

As used herein, "percentage of sequence identity"means the value determined by comparing two optimally aligned sequences over a comparison window, wherein the portion of the polynucleotide sequence in the comparison window may comprise additions or deletions (i. e. , gaps) as compared to the reference sequence (which does not comprise additions or deletions) for optimal alignment of the two se- quences. The percentage is calculated by determining the number of positions at which the identical nucleic acid base or amino acid residue occurs in both se- quences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the window of comparison and multiply- ing the result by 100 to yield the percentage of sequence identity.

Two peptide sequences are"substantially identical"if one peptide is specifically im- munologically reactive with antibodies raised against the second peptide. Thus, a peptide is substantially identical to a second peptide, for example, where the two peptides differ only by a conservative substitution-e. g. the peptides share se- quences except that residue positions which are not identical may differ by conser- vative amino acid changes.

The phrase"specifically immunoreactive with", when referring to an antibody refers to a binding reaction which is determinative of the presence of the protein in the presence of a heterogeneous population of proteins and other biologics. Thus, under designated immunoassay conditions, the specified antibodies bind preferentially to a particular protein and do not bind in a significant amount to other

proteins present in the sample. Specific binding to a protein under such conditions requires an antibody that is selected for its specificity for a particular protein. A variety of immunoassay formats may be used to select antibodies specifically immunoreactive with a particular protein. For example, solid-phase ELISA immunoassays are routinely used to select monoclonal antibodies specifically immunoreactive with a protein. See Harlow and Lane (1988) Antibodies, A Laboratory Manual, Cold Spring Harbor Publications, New York, for a description of immunoassay formats and conditions that can be used to determine specific immunoreactivity.

A"conservative substitution", when describing a protein refers to a change in the amino acid composition of the protein that does not substantially alter the protein's activity. Thus,"conservatively modified variations"of a particular amino acid sequence refers to amino acid substitutions of those amino acids that are not critical for protein activity or substitution of amino acids with other amino acids having similar properties (e. g. , acidic, basic, positively or negatively charged, polar or non- polar, etc. ) such that the substitutions of even critical amino acids do not substantially alter activity. Conservative substitution tables providing functionally similar amino acids are well known in the art. The following is six groups each contain amino acids that are examples of conservative substitutions for one another: 1) Alanine (A), Serine (S), Threonine (T); 2) Aspartic acid (D), Glutamic acid (E); 3) Asparagine (N), Glutamin (Q); 4) Arginine (R), Lysine (K) ; 5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V); and 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W).

See also, Creighton (1984) Proteins, W. H. Freeman and Company. In addition, individual substitutions, deletions or additions which alter, add or delete a single

amino acid or a small percentage of amino acids in an encoded sequence are also "conservatively modified variations".

For the calculation of sequence identity, methods of alignment of nucleotide and amino acid sequences for comparison are well-known in the art. Optimal alignment of sequences for comparison may be conducted, for example, by the local homology algorithm (Best Fit) of Smith and Waterman, Adv. Appl. Math. 2: 482 (1981); by the homology alignment algorithm (GAP) of Needleman and Wunsch, J. Mol. Biol. 48: 443 (1970); by the search for similarity method (Tfasta and Fasta) of Pearson and Lipman, Proc. Natl. Acad. Sci. 85: 2444 (1988); by computerized implementations of these algorithms, including, but not limited to: CLUSTAL in the PC/Gene program by Intelligenetics, Mountain View, Calif., GAP, BESTFIT, BLAST, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group (GCG), 575 Science Dr. , Madison, Wis. , USA; the CLUSTAL program is well described by Higgins and Sharp, Gene 73: 237-244 (1988); Higgins and Sharp, CABIOS 5: 151- 153 (1989); Corpet, et al., Nucleic Acids Research 16: 10881-90 (1988) ; Huang, et al., Computer Applications in the Biosciences 8: 155-65 (1992), and Pearson, et al., Methods in Molecular Biology 24: 307-331 (1994). One preferred program to use for optimal global alignment of multiple sequences is PileUp (Feng and Doolittle, Jour- nal of Molecular Evolution, 25: 351-360 (1987) which is similar to the method de- scribed by Higgins and Sharp, CABIOS, 5: 151-153 (1989) and hereby incorporated by reference).

The BLAST family of programs can be used for database similarity searches and include : BLASTN for nucleotide query sequences against nucleotide database se- quences; BLASTX for nucleotide query sequences against protein database se- quences; BLASTP for protein query sequences against protein database se- quences; TBLASTN for protein query sequences against nucleotide database se- quences; and TBLASTX for nucleotide query sequences against nucleotide data- base sequences. See, Current Protocols in Molecular Biology, Chapter 19, Ausubel, et al., Eds. , Greene Publishing and Wiley-lnterscience, New York (1995), and Alt- schul et al. (1990) J. Mol. Biol. 215: 403-410; Altschul et al., Nucleic Acids Res.

25: 3389-3402 (1997). Software for performing BLAST analyses is publicly available, e. g. , through the National Center for Biotechnology Information (http://www. ncbi. nlm. nih. gov/). This algorithm involves first identifying high scoring

sequence pairs (HSPs) by identifying short words of length W in the query se- quence, which either match or satisfy some positive-valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as the neighborhood word score threshold (Altschul et al., supra). These initial neighborhood word hits act as seeds for initiating searches to find longer HSPs con- taining them. The word hits are then extended in both directions along each se- quence for as far as the cumulative alignment score can be increased. Cumulative scores are calculated using, for nucleotide sequences, the parameters M (reward score for a pair of matching residues; always >0) and N (penalty score for mis- matching residues; always <0). Forsamino acid sequences, a scoring matrix is used to calculate the cumulative score. Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value ; the cumulative score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments; or the end of ei- ther sequence is reached. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. The BLAST program (for nucleotide se- quences) uses as defaults a wordlength (W) of 11, a cutoff of 100, M=5, N=-4, and a comparison of both strands. For amino acid sequences, the BLASTP program uses as defaults a wordlength (W) of 3, a low complexity filter, Gap costs (existence: 11 and extension: 1) and the BLOSUM62 scoring matrix (see Henikoff & Henikoff (1989) Proc. Natl. Acad. Sci. USA 89: 10915). Unless otherwise stated, the term "BLAST"refers to version 2.04.

The BLAST algorithm is also capable of performing a statistical analysis of the simi- larity between two sequences (see, e. g., Karlin & Altschul, Proc. Nat'l. Acad. Sci.

USA 90: 5873-5787 (1993) ). One preferred output is the BLAST"E value". The BLAST E-value measures the statistical significance threshold for reporting protein sequence matches against a database; e. g. if the threshold significance value is 104, then there is a probability of 104 that a match would be expected to occur by chance, according to the stochastic model of Karlin and Altschul (Schaffer, A. A. et al. (1999) Bioinformatics 15: 1000-1011). E values may also be calculated for align- ments generated using any of the other bioinformatics methods described herein.

HMM-SEARCH is another useful program for homology searches, belonging to the HMMER package, which compares a query profile HMM (hidden Markov Model)

against a sequence library. Profile HMMs turn a multiple sequence alignment into a position-specific scoring system suitable for searching databases for remotely ho- mologous sequences. Profile HMM analyses complement standard pairwise com- parison methods for large-scale sequence analysis. Several software implementa- tions and two large libraries of profile HMMs of common protein domains are avail- able (see"HMMER Profile hidden Markov models", Bioinformatics 1998; 14 (9): 755- 763, Eddy SR).

It is envisaged that all the methods described above may be used, for example, to search databases for TA-complex sequences and/or calculate the level of homology between two putative toxin or antitoxin sequences, for example by calculation of an E value or a percentage identity score.

Methods for the evaluation of the ability of a compound to interfere with the toxin- antitoxin complex In a main aspect, the invention relates to methods for the evaluation of the ability of a bioactive compound to interfere with a bacterial toxin-antitoxin complex.'Interfere with'in this context can e. g. be disruption, disturbance as well as prevention of for- mation of the bacterial toxin-antitoxin complex.

Accordingly, the invention relates to a method for the evaluation of the ability of a compound to interfere with a bacterial toxin-antitoxin complex comprising the steps of 1. providing a compound to be evaluated for the ability to interfere with a bacterial toxin-antitoxin complex, 2. providing a first polypeptide comprising a bacterial toxin or a fragment thereof capable of binding an antitoxin, 3. providing a second polypeptide comprising said antitoxin or a fragment thereof capable of binding said toxin, 4. incubating said compound, said first polypeptide and said second polypeptide under conditions allowing binding of said first polypeptide to said second poly- peptide, 5. detecting a signal from said incubation mixture indicative of the degree of bind- ing of said first polypeptide to said second polypeptide,

6. evaluating whether or not the presence of said compound has affected the bind- ing of said first polypeptide to said second polypeptide by comparison of the signal detected in step 5, with a reference value indicative of the binding of said first polypeptide to said second polypeptide in the absence of said compound.

Often, in the above method, the step of evaluating whether or not the presence of said compound has affected the binding of said first polypeptide to said second polypeptide is done by comparison with a control experiment in which said first poly- peptide and said second polypeptide are incubated under conditions allowing bind- ing of said first polypeptide to said second polypeptide in the absence of said com- pound, i. e. the signal detected in this parallel experiment is considered the reference value indicative of the binding of said first polypeptide to said second polypeptide in the absence of said compound. In another preferred embodiment, said reference value is known before the method is carried out, for example the amount of signal is assayed for in the presence of the first and second polypeptide but prior to addition of the compound to be evaluated. Alternatively, said reference value may be well- known to those in the art, such as an absence of detectable signal.

Said methods may be used to qualitatively or quantitatively evaluate the efficacy of a previously identified compound capable of interfering with a bacterial toxin-antitoxin complex, or postulated as being capable of interfering with a bacterial toxin-antitoxin complex.

Alternatively, the aim of the evaluation can e. g. be to identify a compound with the desired activity of interfering with a bacterial toxin-antitoxin complex, for instance to screen libraries of chemical compounds to identify lead compounds. Thus in pre- ferred embodiments, the above method can be used as a method for identification, a method for screening for, or a method for characterising bioactive compounds capa- ble of interfering with a bacterial toxin-antitoxin complex.

Bioactive species of the present invention, which may be used in the methods of the present invention, can be evaluated using in vivo (including cell-based) as well as in vitro evaluation methods as disclosed herein. In one preferred embodiment, said method is capable of directly and/or indirectly detecting a toxin-antitoxin interaction.

Suitable in vitro methods include methods in which the toxin-antitoxin interaction is detected directly, for instance using purified toxin and antitoxin. In one possible set- up, one of the two binding partners is immobilised and the other partner is labelled in such a way as to be capable of producing a signal indicative of the degree of binding of said first polypeptide to said second polypeptide. Said detectable signal may for example be qualitative or quantitative. Interactions of the two binding partners may be detected by assaying for the level of the detectable signal, for example presence or absence of the signal, or for example a quantitative signal.

Signals Preferred signal types include enzymatic activity, such as activity of horseradish peroxidase (HRP) or glucose oxidase. In such cases where the principal signal is from enzymatic activity using an enzyme such as HRP or glucose oxidase, addi- tional reagents are required to visualise the fact that a indicator-moiety/ligand com- plex (immunoreactant) has formed. Such additional reagents for HRP include hy- drogen peroxide and an oxidation dye precursor such as diaminobenzidine. An addi- tional reagent useful with glucose oxidase is 2, 2'-amiho-di- (3-ethyl-benzthiazoline- G-sulfonic acid). Another preferred enzyme activity is activity of beta galactosidase.

The signaling means can also be one or more of a fluorescence-based signal, such as a fluorescent agent that chemically binds to one or more of the polypeptides without denaturing them to form a fluorochrome (dye) that is a useful immunofluo- rescent tracer. Suitable fluorescent labelling agents are fluorochromes such as fluo- rescein isocyanate (FIC), fluorescein isothiocyante (FITC), 5-dimethylamine-1- naphthalenesulfonyl chloride (DANSC), tetramethylrhodamine isothiocyanate (TRITC), lissamine, rhodamine 8200 sulphonyl chloride (RB 200 SC). Other exam- ples of suitable fluorescent materials include umbelliferone, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin and the like. A description of im- munofluorescence analysis techniques is found in DeLuca,"Immunofluorescence Analysis", in Antibody As a Tool, Marchalonis, et al., eds. , John Wiley & Sons, Ltd., pp. 189-231 (1982).

In another embodiment, said signal may be generated by a radiolabelling agent, (for example, wherein radiation (alpha, beta or gamma) produced by decay of a at- tached radioisotope label serves as the signal which can be detected and quanti-

tated by various radiometric methods such as scintillation counting). An example is a radioactive element that produces gamma ray emissions. Elements which them- selves emit gamma rays, such as 1241, 1251, 1281, 132 1 and 5'Cr represent one class of gamma ray emission-producing radioactive element indicating groups. Particularly preferred is 1251. Another group of useful labelling means are those elements such as C, 13F, 150 and 13N which themselves emit positrons, or beta emitters, such as "'indium of 3H. Other suitable radioactive materials include 1310 and 35S.

The level of bound toxin or antitoxin can also be detected using one or more specific antibodies. Detection using antibodies can, in one embodiment, be facilitated by coupling the antibody to another detectable substance, such as an enzyme, a pros- thetic group, a luminescent materials, or a bioluminescent material. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, beta- galactosidase, or acetylcholinesterase ; examples of suitable prosthetic group com- plexes include Streptavidin/biotin and avidin/biotin; an example of a luminescent material includes luminol ; examples of bioluminescent materials include luciferase, luciferin, and aequorin.

The linking of labels, i. e. labelling of polypeptides such as antibodies, is well known in the art. For instance, proteins can be labelled by metabolic incorporation of radio- isotope-containing amino acids provided as a component in the culture medium.

See, for example, Galfre et al., Meth. Enzymol., 73: 3-46 (1981). The techniques of protein conjugation or coupling through activated functional groups are particularly applicable. See, for example, Aurameas, et al., Scand. J. Immunol., Vol. 8 Suppl.

7: 7-23 (1978), Rodwell et al. (1984) Biotech. 3: 889-894, and U. S. Pat. No.

4,493, 795.

In general, the detectability of the signal determines the sensitivity of the evaluation method. The sensitivity is in turn related to both the type of signal employed and the quality and type of equipment available to detect it.

In one preferred embodiment of the present invention, said method for the evalua- tion of the ability of a compound to interfere with a bacterial toxin-antitoxin complex is performed in vitro, for example as a biochemical method, preferably performed using purified toxin and/or purified antitoxin. One or more of said toxins or antitoxins

is preferably fused to a reporter capable of generating a signal, such as any of the signals described herein.

In one preferred in vitro method for the evaluation of the ability of a compound to interfere with a bacterial toxin-antitoxin complex, the antitoxin is purified and immobi- lized, preferably to a solid support, more preferably a well for protein immobilization or a microtiter well, using protocols known in the art. Examples of suitable wells in- clude those provided by Corning Inc. The corresponding toxin is fused to an suitable chemical"reporter"capable of providing a indicative of the degree of binding of said first polypeptide to said second polypeptide, and is for example an enzyme with an easily detectable activity (for example, alkaline phosphatase) or a fluorescently- labelled moiety. The fusion protein is preferably tested for biological activity in vivo before purification. Contacting said toxin with said immobilized antitoxin provides the "signal", for example in the case of alkaline phosphatase being used, any low mo- lecular compound that disrupts the interaction between the TA pair will lead to re- lease of the toxin fused to alkaline phosphatase. It is also envisaged that the same method can be applied with an immobilised toxin and fusion proten comprising the antitoxin.

In one preferred in vitro method for the evaluation of the ability of a compound to interfere with a bacterial toxin-antitoxin complex, the antitoxin is purified and immobi- lized, preferably to a solid support, more preferably a well for protein immobilization or a microtiter well, using protocols known in the art. Examples of suitable wells in- clude those provided by Corning Inc. The corresponding toxin is then incubated with the antitoxin under conditions capable of allowing TA complex formation. The toxin is optionally a fusion protein. Contacting of said toxin to said immobilized antitoxin is detected using one or more specific antibodies, with at least one antibody type being capable of binding to said toxin. At least one of said antibodies is capable of provid- ing a"signal", for example a change in level of enzymatic activity or a change in the level of fluorescence. It is also envisaged that the same method can be applied with an immobilised toxin rather than antitoxin.

In one preferred embodiment of the present invention, the amount of toxin-antitoxin complexes and/or antitoxin complexes are assayed for. In another preferred em- bodiment, the amount of released toxin is assayed for, for example by transferring

the supernatant containing the toxin to a suitable assaying surface, such as a micro- titer well, and performing an assay for the levels of the signal, such as an alkaline phosphatase assay in cases where the signal is alkaline phosphatase activity.

It is preferred that the methods for the evaluation of the ability of a compound to interfere with a bacterial toxin-antitoxin complex are suitable for being automated, using for example robotics and/or automated plate readers known by one skilled in the art. In one preferred embodiment, the one or more compound evaluated is from a commercially available combinatorial chemical library, such as those available from Chemical Diversity Inc.

For maximal sensitivity, it is preferred that substrates yielding fluorescent products should be used to assay for the level of reporter present. Said substrates are pref- erably phosphate substrates, more preferably commercially available fluorescent substrates, such as for example Fluorescein diphosphate-FDP from Molecular Probes Inc. In the case of FDP, the action of alkaline phosphatase causes the hy- drolysis of FDP to fluorescein, that fluoresces with a maximum of 518 nm upon exci- tation with a maximum of 494 nm, which makes this substrate suitable for detection in standard ELISA readers.

In another preferred embodiment of the present invention, the toxin is fluorescently labelled by standard procedures known by those skilled in the art. Toxin and anti- toxin are mixed, for example in microtiter wells, and fluorescence polarization (FP) measured (see Methods 22,61-70 (2000), using e. g. a FP plate reader. The active substances may be identified due to their lower polarization value.

In other preferred embodiments, said method for the evaluation of the ability of a compound to interfere with a bacterial toxin-antitoxin complex is performed in vivo.

In one preferred in vivo method for the evaluation of the ability of a compound to interfere with a bacterial toxin-antitoxin complex, a bacterial two-hybrid system is used to indicate interaction of the TA system components, such as is described by Karimova and coworkers (Proc Natl Acad Sci U S A 95,5752, 1999). The basis of this system is the activation of certain genes, such as lacZ in a bacteria such as E coli, by a complex of interacting proteins, such as the CAP protein in complex with

cAMP. The activated gene creates a detectable signal, such as a change in enzy- matic activity or a change in flourescence levels.

In another preferred in vivo method for the evaluation of the ability of a compound to interfere with a bacterial toxin-antitoxin complex, said TA interaction is monitored using bioluminscence resonance energy transfer (BRET), such as is described by Xu et al. (Xu Y, Piston DW, Johnson CH. A bioluminescence resonance energy transfer (BRET) system: application to interacting circadian clock proteins. Proc Natl Acad Sci U S A 96, 151,1996).

A combination of more than one evaluation method may also be envisaged to be part of the present invention, for example first evaluating large number of com- pounds with an in vitro method, and then screening smaller numbers of compounds with an in vivo method. For example, analogs are evaluated for their activity of dis- rupting TA interactions in vitro and in vivo as disclosed herein, and promising candi- dates are then tested for antibacterial activity using e. g. a bacterial toxicity assay or by monitoring bacterial growth levels.

In another prefered in vivo method, the compound to be evaluated is administered to an individual suffering from, or likely to suffer from, a bacterial disease, and the indi- vidual's disease state used as the signal indicative of the degree of binding of said bacterial toxin to said bacterial antitoxin, using as a reference value the disease state of a healthy individual. Said individual is preferably a laboratory animal, such as a mouse, rat, monkey or rabbit The bioactive species of the present invention may also be identified by optimization protocols, such as an iterative process of systematically modifying the bioactive species structure and retesting. Suitable compounds for use in the evaluation method disclosed herein may also be generated using e. g. computational drug de- sign, structure-based drug design and the like.

Bioactive species capable of activating a polypeptide toxin and/or capable of initiat- ing de novo synthesis of an activated polypeptide toxin

In another aspect of the present invention, a bioactive species is provided, said bio- active species preferably being identifiable using the evaluation methods described above. Said bioactive species is preferably a low molecular weight chemical com- pound.

The bioactive species of the present invention are capable of activating said poly- peptide toxin and/or capable of initiating de novo synthesis of activated polypeptide toxin. By"activating"is meant that said polypeptide toxin becomes capable of having a detrimental effect on said microbial cell, such as, for example, inducing impaired growth of the microbial cell and/or, more preferably, inducing cell death of said mi- crobial cell. In one preferred embodiment of the present invention, said bioactive species is capable of binding to the toxin. In another preferred embodiment of the present invention, said bioactive species is capable of binding to the anti-toxin, wherein said binding preferably prevents said antitoxin from inactivating its cognate toxin. In another preferred embodiment, said bioactive species is capable of binding to the toxin-antitoxin complex, in which case said binding preferably causes direct dissociation of the toxin-antitoxin complex. In another preferred embodiment, said bioactive species promotes degradation of an anti-toxin molecule, thereby increas- ing the levels of free toxin within a bacterial cell. In another preferred embodiment, said bioactive species is capable of destabilising an anti-toxin, thereby optionally (also) promoting degradation of the anti-toxin. In another preferred embodiment, said bioactive species is capable of preventing synthesis of an anti-toxin, thereby increasing the levels of free, activated toxins within a bacterial cell. In another pre- ferred embodiment, said bioactive species is capable of promoting the synthesis of a toxin compound, thereby increasing the levels of free (i. e. not bound within a TA complex) active toxin in a bacterial cell. In another preferred embodiment, said bio- active species is capable of increasing the stability of a toxin, thereby promoting the toxic effect of the toxin molecules on a bacterial cell.

Said bioactive species is preferably organic in nature. In one preferred embodiment said bioactive species comprises or essentially consists of one or more of the follow- ing: a-peptides, ß-peptides,-peptides, bpeptides, mono-, di-and tri-substituted a- peptides, p-peptides, y-peptides, m-peptides, peptides wherein the amino acid resi- dues are in the L-form or in the D-form, vinylogous polypeptides, glycopoly-peptides,

polyamides, vinylogous sulfonamide peptide, polysulfonamide, conjugated peptides comprising e. g. prosthetic groups, polyesters, polysaccharides, polycarbamates, polycarbonates, polyureas, polypeptidylphosphonates, polyurethanes, azatides, oligo N-substituted glycines, polyethers, ethoxyformacetal oligomers, poly- thioethers, polyethylene glycols (PEG), polyethylenes, polydisulfides, polyarylene sulfides, polynucleotides, PNAs, LNAs, morpholinos, oligo pyrrolinone, polyoximes, polyimines, polyethyleneimines, polyimides, polyacetals, polyacetates, polystyrenes, polyvinyl, lipids, phospholipids, glycolipids, polycyclic compounds comprising e. g. aliphatic or aromatic cycles, including polyheterocyclic compounds, proteoglycans, and/or polysiloxanes.

Yet further preferred molecules are those comprising a scaffold structure comprising a plurality of covalently linked functional entities selected from the group consisting of a-peptides, p-peptides, y-peptides, m-peptides, mono-, di-and tri-substituted a- peptides, p-peptides, y-peptides, co-peptides, peptides wherein the amino acid resi- dues are in the L-form or in the D-form, vinylogous polypeptides, glycopoly-peptides, polyamides, vinylogous sulfonamide peptides, polysulfonamides, conjugated pep- tides comprising e. g. prosthetic groups, polyesters, polysaccharides, polycar- bamates, polycarbonates, polyureas, polypeptidylphosphonates, polyurethanes, azatides, oligo N-substituted glycines, polyethers, ethoxyformacetal oligomers, poly- thioethers, polyethylene glycols (PEG), polyethylenes, polydisulfides, polyarylene sulfides, polynucleotides, PNAs, LNAs, morpholinos, oligo pyrrolinones, polyoximes, polyimines, polyethyleneimines, polyimides, polyacetals, polyacetates, polystyrenes, polyvinyl, lipids, phospholipids, glycolipids, polycyclic compounds comprising e. g. aliphatic or aromatic cycles, including polyheterocyclic compounds, proteoglycans, and polysiloxanes, and wherein the plurality of functional entities is preferably from 2 to 200, for example from 2 to 100, such as from 2 to 80, for example from 2 to 60, such as from 2 to 40, for example from 2 to 30, such as from 2 to 20, for example from 2 to 15, such as from 2 to 10, such as from 2 to 8, for example from 2 to 6, such as from 2 to 4, for example 2, such as from 3 to 100, for example from 3 to 80, such as from 3 to 60, such as from 3 to 40, for example from 3 to 30, such as from 3 to 20, such as from 3 to 15, for example from 3 to 15, such as from 3 to 10, such as from 3 to 8, for example from 3 to 6, such as from 3 to 4, for example 3, such as from 4 to 100, for example from 4 to 80, such as from 4 to 60, such as from 4 to 40, for example from 4 to 30, such as from 4 to 20, such as from 4 to 15, for example

from 4 to 10, such as from 4 to 8, such as from 4 to 6, for example 4, for example from 5 to 100, such as from 5 to 80, for example from 5 to 60, such as from 5 to 40, for example from 5 to 30, such as from 5 to 20, for example from 5 to 15, such as from 5 to 10, such as from 5 to 8, for example from 5 to 6, for example 5, such as from 6 to 100, for example from 6 to 80, such as from 6 to 60, such as from 6 to 40, for example from 6 to 30, such as from 6 to 20, such as from 6 to 15, for example from 6 to 10, such as from 6 to 8, such as 6, for example from 7 to 100, such as from 7 to 80, for example from 7 to 60, such as from 7 to 40, for example from 7 to 30, such as from 7 to 20, for example from 7 to 15, such as from 7 to 10, such as from 7 to 8, for example 7, for example from 8 to 100, such as from 8 to 80, for ex- ample from 8 to 60, such as from 8 to 40, for example from 8 to 30, such as from 8 to 20, for example from 8 to 15, such as from 8 to 10, such as 8, for example 9, for example from 10 to 100, such as from 10 to 80, for example from 10 to 60, such as from 10 to 40, for example from 10 to 30, such as from 10 to 20, for example from 10 to 15, such as from 10 to 12, such as 10, for example from 12 to 100, such as from 12 to 80, for example from 12 to 60, such as from 12 to 40, for example from 12 to 30, such as from 12 to 20, for example from 12 to 15, such as from 14 to 100, such as from 14 to 80, for example from 14 to 60, such as from 14 to 40, for exam- ple from 14 to 30, such as from 14 to 20, for example from 14 to 16, such as from 16 to 100, such as from 16 to 80, for example from 16 to 60, such as from 16 to 40, for example from 16 to 30, such as from 16 to 20, such as from 18 to 100, such as from 18 to 80, for example from 18 to 60, such as from 18 to 40, for example from 18 to 30, such as from 18 to 20, for example from 20 to 100, such as from 20 to 80, for example from 20 to 60, such as from 20 to 40, for example from 20 to 30, such as from 20 to 25, for example from 22 to 100, such as from 22 to 80, for example from 22 to 60, such as from 22 to 40, for example from 22 to 30, such as from 22 to 25, for example from 25 to 100, such as from 25 to 80, for example from 25 to 60, such as from 25 to 40, for example from 25 to 30, such as from 30 to 100, for example from 30 to 80, such as from 30 to 60, for example from 30 to 40, such as from 30 to 35, for example from 35 to 100, such as from 35 to 80, for example from 35 to 60, such as from 35 to 40, for example from 40 to 100, such as from 40 to 80, for exam- ple from 40 to 60, such as from 40 to 50, for example from 40 to 45, such as from 45 to 100, for example from 45 to 80, such as from 45 to 60, for example from 45 to 50, such as from 50 to 100, for example from 50 to 80, such as from 50 to 60, for exam- ple from 50 to 55, such as from 60 to 100, for example from 60 to 80, such as from

60 to 70, for example from 70 to 100, such as from 70 to 90, for example from 70 to 80, such as from 80 to 100, for example from 80 to 90, such as from 90 to 100.

The bioactive species to be synthesised in accordance with the present invention are preferably"small molecules", by which is meant molecules having a molecular weight (MW) of less than 10000 Daltons, such as less than 8000 Daltons, for exam- ple less than 6000 Daltons, such as less than 5000 Daltons, for example less than 4000 Daltons, for example less than 3500 Daltons, such as less than 3000 Daltons, for example less than 2500 Daltons, for example less than 2000 Daltons, such as less than 1800 Daltons, for example less than 1600 Daltons, for example less than 1400 Daltons, such as less than 1200 Daltons, for example less than 1000 Daltons.

The functional entities of the above molecules can be linked by a chemical bond selected from the group of chemical bonds consisting of peptide bonds, sulfonamide bonds, ester bonds, saccharide bonds, carbamate bonds, carbonate bonds, urea bonds, phosphonate bonds, urethane bonds, azatide bonds, peptoid bonds, ether bonds, ethoxy bonds, thioether bonds, single carbon bonds, double carbon bonds, triple carbon bonds, disulfide bonds, sulfide bonds, phosphodiester bonds, oxime bonds, imine bonds, imide bonds, including any combination thereof.

In one embodiment the chemical bond linking at least some of the functional entities of the molecule is preferably formed by a reaction of a nucleophile group of a first functional entity with an ester or thioester of another functional entity. The linker of the functional entity bearing the thioester group is preferably cleaved simultaneously with the formation of the bond resulting in a transfer of the functional entity or a part thereof to the nucleophilic functional entity. The nucleophile group is preferably se- lected from-NH2, H2NHN-, HOHN-, H2N-C (O)-NH-.

The backbone structure of said bioactive species can, for example, comprise or es- sentially consist of one or more molecular group (s) selected from-NHN (R) CO- ;- NHB (R) CO- ;-NHC (RR') CO- ;-NHC (=CHR) CO- ;-NHC6 H4 CO- ;-NHCH2 CHRCO- ; <BR> <BR> <BR> -NHCHRCH2 CO- ;-COCH2- ;-COS- ;-CONR- ;-COO- ;-CSNH- ;-CH2 NH- ;-<BR> <BR> <BR> <BR> <BR> CH2CH2-;-CH2 S-;-CH2 SO-;-CH2SO2-;-CH (CH3) S-;-CH=CH-;-NHCO-;- NHCONH- ;-CONHO- ;-C (=CH2) CH2- ;-P02-NH- ;-P02-P02 S02NH-- ; and lactams.

The following properties may also be used to define the bioactive species of the present invention: the number of rotatable bonds (RTB) the number of rings (RNG) the number of hydrogen bond donors (HDO) the number of hydrogen bond acceptors (HAC) the octanol-water partition coefficient (log P) molar refractivity (MR) In preferred embodiments of the present invention, said bioactive species falls within one or more of the following limits : <BR> <BR> <BR> <BR> 3 # HDO # 5, more preferably 0 # HDO # 2<BR> <BR> <BR> <BR> <BR> <BR> 2 # HAC # 9<BR> <BR> <BR> <BR> <BR> <BR> 2 # RTB # 8<BR> <BR> <BR> <BR> <BR> <BR> 1 # RNG # 4 -0.4 # log P # 5.6, more preferably around 2.5 40 sMR S130, more preferably around 97.

The bioactive species preferably comprises any amino acid sequence of at least about 1 to 60 amino acids in length and may be derived from the expression of nu- cleotide sequences which are prepared by any one of a variety of methods such as, for example, random synthetic generation, or using naturally-occurring genomes as exemplified herein. The use of larger fragments, particularly employing randomly sheared nucleic acid derived from bacterial, yeast or animal genomes, is not ex- cluded.

In another preferred embodiment, the bioactive species is expressed as a fusion protein with a peptide sequence capable of enhancing uptake of the peptide by an isolated cell such as, for example, when the subject peptide is synthesized ex vivo and added to isolated cells in culture. In a preferred embodiment, the peptide se- quence capable of enhancing, increasing or assisting penetration or uptake is func- tional in bacterial cells.

The bioactive species may also be expressed in a conformationally constrained

form. For example, amino acid sequences which are expressed in a conformation- ally constrained form may be expressed within a second polypeptide as a fusion protein such that they are effectively"nested"in the secondary structure of the sec- ond polypeptide. Alternatively, a peptide, oligopeptide or polypeptide may be circu- larized within a loop of disulphide bonds to limit conformational diversity, such as, for example, by expressing a peptide within oxidized flanking cysteine residues. This may be particularly beneficial where the amino acid sequences are nested within a surface-exposed or functional site of a protein, such that they are accessible to the interaction of interest. For example, the peptide may be expressed within a thiore- doxin (Trx) polypeptide loop.

In one preferred embodiment of the present invention, said bioactive species com- prises at least one heterocyclic ring, such as an aromatic heterocycle or, more pref- erably, a nonaromatic heterocyclic rings. In another preferred embodiment, said bioactive species comprises at least one tertiary aliphatic amines. In another pre- ferred embodiment, said bioactive species comprises at least one alcoholic OH group. In another preferred embodiment, said bioactive species comprises at least one carboxamide. In another preferred embodiment, said bioactive species com- prises at least one benzene ring.

In a preferred embodiment of the present invention, said bioactive species is pref- erably lipophilic, and capable of penetrating a cell membrane. In another preferred embodiment, said molecule is encapsulated in a lipophilic carrier, such as a micelle or liposome, to enable effective penetration of cell membranes. In another preferred embodiment, said bioactive species is preferably non-immunogenic.

In another preferred embodiment of the present invention, said bioactive species is classified as a"drug"using the scoring scheme disclosed in Sadowski et al.,"A scoring scheme for discriminating between drugs and non-drugs", Combinatorial Chemistry and Molecular Modelling, vol. 41, Issue 18, August 27,1998 p 3325- 3329.

In another preferred embodiment of the present invention, said bioactive species passes the"rule of 5"test, a probability scheme that estimates oral absorption, pro- posed by Lipinski et al. [Adv. Drug Deliv. Rev. , 23 (1997) 3].

In one embodiment, the bioactive species is designed to bind to, or close to, an area of an antitoxin and/or toxin that interacts with its corresponding toxin or antitoxin (i. e. a binding interface). Without being bound by theory, it is believed that this would disrupt the binding interface between said toxin and antitoxin, preventing or reducing binding and thus preventing or reducing TA complex formation, thus preventing neu- tralisation of the toxin. Thus, in one embodiment of the present invention, the bioac- tive species of the present invention is a reduced-toxicity variant of the toxin, which causes antitoxin inactivation. Such reduced-toxicity variant may be a variant of a toxin from any of the following toxin/antitoxin systems: parDE systems chp systems (chpA locus has also been called mazEF) higBA systems (HigB toxin, HigA antitoxin) phd/doc systems ccdAB systems (ccdA antitoxin, ccdB toxin) vapBC systems (also known as vagCD or STBORF1 and STBORF2) Preferably, said variant is a reduced-toxicity variant of the MazF toxin.

Thus, said variant may be a peptide comprising, consisting of, or consisting essen- tially of, amino acid residues 15-31 of the E. coli MazF toxin (VDFDPTKGSEQAGHRPA-SEQ ID NO: 722), or homologue and/or fragment thereof. Said homologue and/or fragment may be e. g. less than 16 amino acids long and is preferably at least 4, for example at least 6, such as at least 8, for example at least 10, such as at least 12, for example at least 14, such as at least 15 amino ac- ids long. Suitable"homologues thereof'include homologous polypeptide sections in SEQ ID NO : 155 and 160, such as SVMLTVPPA LLNALSLGTD N (SEQ ID NO: 723) and VGFDPASGHEQQGAGRP (SEQ ID NO: 724). Further suitable homologues include polypeptide sections homologous to VDFDPTKGSEQAGHRP A (SEQ ID NO: 722) in the MazF toxin polypeptides with SEQ ID NO: 161-205. Further suitable homologues include polypeptide sections homologous to VDFDPTKGSEQAGHRP A (SEQ ID NO: 722) in any of the MazF toxin polypeptides described in Example 5 (results shown in Table 2). (A polypeptide section (preferably used in the invention as an isolated polypeptide in itself) is defined as"Homologous"to a comparison polypeptide if the homology value has an E value of 10-4 or less (e. g. 10-5 or less, e. g 10-6 or less, e. g 10-7 or less, e. g 10-8 or less, e. g 10-9 or less, e. g 10-"or less) when calculated using the BLAST algorithm version (2.04) set to the default pa- rameters defined herein.)

Alternatively, said variant may be a peptide comprising, consisting of, or consisting essentially of, amino acid residues 31-50 of the E. coli MazF toxin (AWLSPFMYN NKTGMCLCVP-SEQ ID NO: 725), or homologue and/or fragment thereof. Said fragment and/or homologue may be e. g. less than 21 amino acids long and is pref- erably at least 4, for example at least 6, such as at least 8, for example at least 10, such as at least 12, for example at least 14, such as at least 16, for example at least 18, amino acids long. Suitable"homologues thereof"include homologous polype- tide sections in SEQ ID NO : 155 and 160, such as NEVGMVIDNGRLIVEPYRRPQYSLAELLAQ CDP (SEQ ID NO: 726) and ALVLSVQAFNQLGMTLVAP (SEQ ID NO: 727). Further suitable homologues in- clude polypeptide sections homologous to AWLSPFMYNNKTGMCLCVP (SEQ ID NO: 725) in the MazF toxin polypeptides with SEQ ID NO: 161-205. Further suitable homologues include polypeptide sections homologous to AWLSPFMYNNKTGMCLCVP SEQ ID NO: 725) in any of the MazF toxin polype- tides described in Example 5 (results shown in Table 2).

Equally preferably, said variant may be a peptide comprising, consisting of, or con- sisting essentially of, amino acid residues 50-79 of the E. coli MazF toxin (PCTTQSKGYPF EWLSGQERD GVALADQVK-SEQ ID NO: 728), or homologue and/or fragment thereof. Said fragment and/or homologue may be e. g. less than 32 amino acids long and is preferably at least 4, for example at least 6, such as at least 8, for example at least 10, such as at least 12, for example at least 14, such as at least 16, for example at least 18, such as at least 20, for example at least 22, such as at least 24, for example at least 26, such as at least 28, amino acids long. Suit- able fragments include, but are not restricted to a fragment selected from PCTTQS (SEQ ID NO: 729), KGYPF (SEQ ID NO: 730), EWLS (SEQ ID NO: 731), GQERD (SEQ ID NO: 732), GVALA (SEQ ID NO: 733), or DQVK (SEQ ID NO: 734). Suit- able"homologues thereof"include homologous polypeptide sections in SEQ ID NO : 155 and 160. Further suitable homologues include polypeptide sections ho- mologous to PCTTQSKGYPFEWLSGQERDGVALADQVK (SEQ ID NO: 728) in the MazF toxin polypeptides with SEQ ID NO: 161-205. Further suitable homologues include polypeptide sections homologous to PCTTQSKGYPFEWLSGQERDG- VALADQVK (SEQ ID NO: 728) in any of the MazF toxin polypeptides described in Example 5 (results shown in Table 2).

Equally preferably, said variant may be a peptide comprising, consisting of, or con- sisting essentially of, amino acid residues 86-109 of the E. coli MazF toxin (RGATKKGTVAPEELQLIKAKINVL-SEQ ID NO: 735), or homologue and/or frag- ment thereof. Said homologue and/or fragment may be e. g. less than 25 amino acids long and is preferably at least 4, for example at least 6, such as at least 8, for example at least 10, such as at least 12, for example at least 14, such as at least 16, for example at least 18, such as at least 20, such as at least 22, amino acids long. Suitable fragments include, but are not restricted to, RGATK (SEQ ID NO: 736), KGTVA (SEQ ID NO: 737), PEELQ (SEQ ID NO: 738), LIKA (SEQ ID NO: 739), or KINVL (SEQ ID NO: 740). Suitable"homologues thereof'include homolo- gous polypeptide sections in SEQ ID NO : 155 and 160. Further suitable homologues include polypeptide sections homologous to RGATKKGTVAPEELQLIKAKINVL (SEQ ID NO: 735), in the MazF toxin polypeptides with SEQ ID NO: 161-205. Fur- ther suitable homologues include polypeptide sections homologous to RGATKKGTVAPEELQLIKAKINVL (SEQ ID NO: 735), in any of the MazF toxin polypeptides described in Example 5 (results shown in Table 2).

In another embodiment of the present invention, the bioactive species of the present invention is an antitoxin variant, said antitoxin variant acting to bind to, but not inac- tivate, its cognate toxin. Said antitoxin variant may be a variant of an antitoxin from any of the following toxin/antitoxin systems: parDE systems chp systems (chpA locus has also been called mazEF) higBA systems (HigB toxin, HigA antitoxin) phd/doc systems ccdAB systems (ccdA antitoxin, ccdB toxin) vapBC systems (also known as vagCD or STBORF1 and STBORF2).

Preferably, said antitoxin variant is a variant of the MazE antitoxin. Said variant of the MazE antitoxin may be a peptide comprising, consisting of, or consisting essen- tially of, amino acid residues 29-32 of the E. coli MazE antitoxin (IDDE-SEQ ID NO: 741), or homologue and/or fragment thereof, such as IDD, DDE or DD. Said frag- ment and/or homologue may be e. g. less than 6 amino acids long and is preferably at least 2, for example at least 3, such as at least 4, for example at least 5 amino acids long. Suitable"homologues thereof"include homologous polypeptide sections in SEQ ID NO: 156,157, 158 or 159.

Alternatively, said variant of the MazE antitoxin may be a peptide comprising, con- sisting of, or consisting essentially of, amino acid residues 48-53 of the E. coli MazE antitoxin (RKEPVF-SEQ ID NO: 742), or homologue and/or fragment thereof, such as RKE, KEPV or PVF. Said fragment and/or homologue may be e. g. less than 7 amino acids long and is preferably at least 2, for example at least 3, such as at least 4, for example at least 5 amino acids long. Suitable"homologues thereof'include homologous polypeptide sections in SEQ ID NO: 156,157, 158 or 159.

Alternatively, said variant of the MazE antitoxin may be a peptide comprising, con- sisting of, or consisting essentially of, amino acid residues 68-76 of the E. coli MazE antitoxin (HENIDWGEP-SEQ ID NO: 743), or homologue and/or fragment thereof.

Said homologue and/or fragment may be e. g. less than 10 amino acids long and is preferably at least 4, for example at least 6, such as at least 8 amino acids long.

Suitable fragments include, but are not restricted to, HENI (SEQ ID NO: 744), NIDW (SEQ ID NO: 745), or DWGEP (SEQ ID NO: 746). Suitable"homologues thereof' include homologous polypeptide sections in SEQ ID NO: 156,157, 158 or 159.

Alternatively, said variant of the MazE antitoxin may be a peptide comprising, con- sisting of, or consisting essentially of, amino acid residues 54-67 of the E. coli MazE antitoxin (LAELVNDITPENL-SEQ ID NO: 747), or homologue and/or fragment thereof. Said homologue and/or fragment may be e. g. less than 13 amino acids long and is preferably at least 4, for example at least 6, such as at least 8, for exam- ple at least 10, such as at least 12 amino acids long. Suitable fragments include, but are not restricted to, LAEL (SEQ ID NO: 748), ELVN (SEQ ID NO: 750), VNDIT (SEQ ID NO: 751), or PENL (SEQ ID NO: 752). Suitable"homologues thereof"in- clude homologous polypeptide sections in SEQ ID NO: 156,157, 158 or 159.

Thus, preferred bioactive species may be any of the following sequences (or a fragment or homologue thereof) : FTLAELVN (SEQ ID NO: 753), NDITPENLHENIDW (SEQ ID NO: 754), PVRKE PVFTLAELV (SEQ ID NO: 755), TPENLHEN IDWGEPK (SEQ ID NO: 756), LAELVNDITPENL (SEQ ID NO: 757).

Most preferably, said bioactive species is LAELVNDITPENLHE (SEQ ID NO: 758), or a fragment or homologue thereof.

In another preferred embodiment of the present invention, said antitoxin variant is a variant of the RelB antitoxin. Said variant of the RelB antitoxin may be a peptide comprising, consisting of, or consisting essentially of, amino acid residues 9-23 of the E. coli MazE antitoxin (DDELKARSYAALEKM-SEQ ID NO: 759), or homologue and/or fragment thereof. Said homologue and/or fragment may be e. g. less than 16 amino acids long and is preferably at least 4, for example at least 6, such as at least 8, for example at least 10, such as at least 12, for example at least 14 amino acids long. Suitable fragments include, but are not restricted to, ELKARSY (SEQ ID NO: 760), RSYAA (SEQ ID NO: 761), ELKARSYAALEKM (SEQ ID NO: 762), or RID- DELKARSYAALE (SEQ ID NO: 763). Suitable"homologues thereof'include ho- mologous polypeptide sections in any of SEQ ID NO: 1,3, 5,7, 9,11, 13 or 15.

In another preferred embodiment of the present invention, said antitoxin variant is a variant of the RelB antitoxin. Said variant of the RelB antitoxin may be a peptide comprising, consisting of, or consisting essentially of, amino acid residues 39-53 of the E. coli MazE antitoxin (ADNERLPFKQTL LSD-SEQ ID NO: 764), or homologue and/or fragment thereof. Said homologue and/or fragment may be e. g. less than 16 amino acids long and is preferably at least 4, for example at least 6, such as at least 8, for example at least 10, such as at least 12, for example at least 14, amino acids long. Suitable fragments include, but are not restricted to, ADNE (SEQ ID NO: 765), RLPF (SEQ ID NO: 766), KQTL (SEQ ID NO: 767), or LSD (SEQ ID NO: 768).

Suitable"homologues thereof'include homologous polypeptide sections in any of SEQIDNO : 1,3, 5,7, 9,11, 13 or 15.

One skilled in the art is also aware that peptides, such as the above-mentioned pep- tides, do not have to comprise natural peptide bonds in order to maintain the re- quired activity of activating a bacterial toxin. Suitable alternative chemical bonds that may be used to replace one or more of the peptide bonds (such as to replace all the peptide bonds) include, but are not restricted to, - NHN (R) CO- - NHB (R) CO- - NHC (RR') CO- - NHC (=CHR) CO-

-NHC6H4CO-<BR> -NHCH2CHRCO-<BR> -NHCHRCH2CO- , and lactam structures, -COCH2- -COS- -CONR -COO- -CSNH- <BR> -CH2NH-<BR> -CH2CH2-<BR> -CH2S-<BR> -CH2SO- -CH2SO2- -CH (CH3) S- -CH=CH- <BR> - NHCO-<BR> - NHCONH- -CONHO- - C (=CH) CH2- Wherein"R"represents the amino acid side chain.

Aptamers In one preferred embodiment of the present invention, the bioactive species of the present invention is an aptamer. Aptamers are macromolecules comprised of nu- cleic acid, such as RNA or DNA, that bind tightly to a specific molecular target. In one embodiment of the present invention, said aptamer is 15-60 bases. It is usual that the chain of nucleotides comprising the aptamer forms intramolecular interac- tions that fold the molecule into a complex three-dimensional shape. The shape of the aptamer allows it to bind tightly against the surface of its target molecule, herein preferably a toxin, antitoxin or TA complex. Because an extraordinary diversity of molecular shapes exist within the universe of all possible nucleotide sequences, aptamers may be obtained for a wide array of molecular targets, including most pro- teins and many small molecules. Aptamers are chemically stable to all but the harshest environmental conditions and can be boiled or frozen without loss of activ-

ity. They may be produced on the benchtop using standard molecular biological techniques or they may be chemically synthesized at microgram to kilogram scales.

As synthetic molecules, they are amenable to a nearly infinite variety of modifica- tions designed to optimize their properties for a specific application. They may be circularized, linked together in pairs, or clustered onto the surface of a fat globule.

For in vivo applications, for instance in a pharmaceutical formulation, aptamers can be modified to dramatically reduce their sensitivity to degradation by enzymes in the blood. Other chemical appendages can alter their biodistribution or plasma resi- dence time following, for example, intravenous injection. This plasticity is a distinct advantage of aptamers over other types of molecular ligands, such as monoclonal antibodies, where chemical modification is often variable, difficult to control, and may harm the function of the molecule.

The surface area of interaction between an aptamer and its molecular target is rela- tively large, so even small changes in the target molecule can disrupt aptamer asso- ciation. Thus, aptamers can distinguish between closely related but non-identical members of a protein family, or between different functional or conformational states of the same protein. In a striking example of specificity, an aptamer to the small molecule theophylline (1, 3-dimethylxanthine) binds with 10, 000-fold lower affinity to caffeine (1,3, 7-trimethylxanthine) that differs from theophylline by a single methyl group.

In addition to high specificity, aptamer have very high affinities to their targets. Typi- cally aptamers generated against proteins have affinities in the picomolar to low nanomolar range.

Example of one possible method of aptamer selection-SELEX Systematic evolution of ligands by exponential enrichment (SELEX) (see also Gold et al.,"Diversity of Oligonucleotide functions", Annu Rev Biochem. 1995 ; 64: 763-97) is an iterative process used to identify an aptamer to a chosen molecular target.

The method relies on standard molecular biological techniques and can be carried out manually or in an automated fashion. The process can be broken down concep-

tually into four steps: (1) pool preparation, (2) selection, (3) amplification and (4) aptamer isolation.

(1) Pool preparation To begin, a large"library"of nucleic acid molecules is generated. Each molecule in the library (often as many as 1015 different compounds) contains a unique nucleotide sequence that can, in principle, adopt a unique three-dimensional shape. A very few of these molecules-the aptamers-present a surface that is complementary to the target molecule.

(2) Selection partitioning The selection step is designed to find those molecules with the greatest affinity for the target of interest. The library of nucleotide sequences is exposed to the target (a protein, small molecule, or supramolecular structure) and allowed to incubate for a period of time. The molecules in the library with weak or no affinity for the target will, on average, remain free in solution while those with some capacity to bind will tend to associate with it.

Any one of several methods is used to physically isolate the aptamer target com- plexes from the unbound molecules in the mixture, effectively separating the wheat from the chaff on a molecular scale. The unbound molecules are discarded. The target-bound molecules, among which are the highest affinity aptamers, are purified away from the target and used for the subsequent steps in the SELEX process.

(3) Amplification The captured, purified sequences are copied enzymatically, or"amplified", to gener- ate a new library of molecules that is substantially enriched for those that can bind to the target. The enriched library is used to initiate a new cycle of selection, partition- ing and amplification.

(4) Aptamer isolation After 5-15 cycles of the complete process, the library of molecules is reduced from 1015 of unique sequences to a small number that bind tightly to the target of interest.

Individual molecules in the mixture are then isolated, their nucleotide sequences are determined, and their properties with respect to binding affinity and specificity are

measured and compared. In most cases, isolated aptamers are further refined to eliminate any nucleotides that do not contribute to target binding or aptamer struc- ture. Aptamers truncated to their core binding domain typically range in length from 15 to 60 nucleotides.

Photoaptamers (such as those produced by SomaLogic) may be created by substi- tuting a brominate deoxyuridine (BrdU) for the thymidine (T) normally found in DNA, aptamers take on the ability to crosslink to specific sites on their target proteins.

Photoaptamers thus add a second dimension of specificity, since they recognize both the complex shape and charge distribution of their targets and the presence of specific amino acid residues at specific sites.

Methods suitable for selecting an aptamer suitable for use in the present invention, and further information on aptamers, are disclosed in the following US patents, in- corporated herein by reference to their patent numbers: 6,482, 594; 6,458, 543; 6,458, 539; 6,376, 190; 6,344, 318 ; 6,242, 246; 6,184, 364; 6,001, 577; 5,958, 691; 5, 874, 218; 5,853, 984; 5,843, 732; 5,843, 653; 5,817, 785; 5,763, 177; 5,696, 249; 5,660, 985; 5,595, 877; 5,567, 588; and 5,270, 163.

Other single molecule selection methods suitable for identifying or assessing small molecule compounds suitable for use in the present invention are disclosed in US Patent Application 2002/0034757.

Aptamers may be generated against any of the toxins, antitoxins and TA complexes described herein. In all cases of aptamer evolution discussed herein, it is preferred that the aptamer is designed to bind to, or close to, an area of an antitoxin and/or toxin that interacts with its corresponding toxin or antitoxin (i. e. a binding interface).

Without being bound by theory, it is believed that this would increase the likelihood of success of identifying a suitable bioactive species as it would disrupt the binding interface between said toxin and antitoxin, preventing or reducing binding and thus preventing or reducing TA complex formation, thus preventing neutralisation of the toxin. In the most preferred embodiment of the present invention, it is preferred that the bioactive species, such as an aptamer, is designed to bind one or more binding

interface of a bacterial antitoxin, such as an antitoxin from one or more of the follow- ing TA systems: parDE systems chp systems (chpA locus has also been called mazEF) higBA systems (HigB toxin, HigA antitoxin) phd/doc systems ccdAB systems (ccdA antitoxin, ccdB toxin) vapBC systems (also known as vagCD or STBORF1 and STBORF2) Biotech evolutionary methods In one embodiment of the present invention, it is envisaged that a potential bioactive species for use in the methods of the present invention may have been identified using a strategy comprising a method, known by those skilled in the art, suitable for use in evolving small molecules.

Biotech evolutionary methods, including combinatorial libraries and phage-display technology (see e. g. Parmley, S. F. and Smith, G. P. (1988) Gene 73,305-318 ; Scott, J. K. and Smith, G. P. (1990) Science 249,386-390 ; Smith, G. P. (1993) Gene 128,1-2.), are used in the search for novel ligands of diagnostic, biomedical and pharmaceutical use (for reviews, see Cortese, R. (ed. ) (1996) Combinatorial libraries: Synthesis, Screening and Application potential ; Walter de Gruyter, Berlin and Collins, J. (1997) Phage display. In Moos, W. H. et al. (eds) Annual reports in combinatorial chemistry and molecular diversity. Vol. 1., ESCOM Science publ., Leiden. pp. 210-262). These methods use empirical procedures to select molecules with required characteristics, e. g. binding properties, from large populations of vari- ant gene products. Evolutionary methods also include SELEX (see section on ap- tamers).

Phage display methods One such suitable evolutionary method that may have been used to generate the bioactive species of the present invention is a phage display method.

Phage display is a method to individually display up to tens of billions of peptides and proteins, including for example human antibodies and enzymes, on the surface of a filamentous phage, a bacterial virus. Preferred phage for use in the present in-

vention include, but are not restricted to, M13, fd or fl phage. Phage display can be used to produce and search through large collections, or libraries, of peptides and proteins to rapidly identify those compounds that bind with high affinity and high specificity to targets of interest, in this case a bacterial toxin, antitoxin or TA com- plex.

The phage display process generally consists of the following steps: (1) generating one or more phage libraries, (2) screening the phage display libraries to select bind- ing compounds with high affinity and high specificity to a target, and (3) producing and evaluating the selected binding compounds.

Phage display libraries can contain billions of potential binding compounds, that may be rationally-designed variations of a particular peptide or protein framework. The size and diversity of the libraries improves the likelihood of identifying compounds with high specificity (the ability to bind to the target and not to other, closely related molecules) and high affinity (strength of binding to the target).

In these method types, gene libraries are generated containing extremely large number (for example, 106 to 101°) of variants. The variant gene segments are fused to a coat protein gene of a filamentous bacteriophage, and the fusion gene is in- serted into the genome of the phage or of a phagemid. A phagemid is defined as a plasmid containing the packaging and replication origin of a filamentous bacterio- phage. This latter property allows the packaging of the phagemid genome into a phage coat when it is present in an Escherichia coli host strain infected with a fila- mentous phage (superinfection). The packaged particles produced, be they phage or phagemid, display the fusion protein on the surface of the particles secreted into the medium. Such packaged particles are able to inject their genomes into a new host bacterium, where they can be propagated as phage or plasmids, respectively.

The special property of the system lies in the fact that since the packaging takes place in individual cells usually infected by a single variant phage/phagemid, the particles produced on propogation contain the gene encoding the particular variant displayed on the particle's surface. Several cycles of affinity selection for clones ex- hibiting the required properties due to the particular property of the variant protein displayed, e. g. binding to a particular target molecule immobilized on a surface, fol- lowed by amplification of the enriched clones leads to the isolation of a small num-

ber of different clones having these properties. The primary structure of these vari- ants can then be rapidly elucidated by sequencing the hypermutated segment of the variant gene.

Phage display technology can be applied in an automated format to many targets simultaneously to discover specific, high-affinity compounds, including antibodies, such as human monolclonal antibodies, for each target.

A selected phage can be replicated into thousands of identical copies in less than a day. Once generated, a phage display library can be amplified and stored so that it may be used for an unlimited number of screenings.

Phage display libraries are screened to identify binding compounds with high affinity and high specificity for the desired target. This information can be used to design successive generations of phage display libraries to further optimize leads. For ex- ample, Dyax has demonstrated between a 10-and 100-fold improvement in binding affinity with second generation phage display libraries.

Example of suitable phage display libraries : 1) Structured peptide libraries : Disulfide constrained cyclic peptide libraries may be used, e. g. in one library pro- duced by Dyax, the peptides within the cyclized structure range in size from six to twelve amino acids. Amino acids both within and outside the cyclized structure are selected for variation, and the number of distinct peptide structures in each library typically exceeds 10 billion. The resulting peptides are chemically synthesizable and are amenable to chemical modification, such as attachment to a chromatographic support.

2) Protein Libraries Phage libraries based on well-characterized protein structures may also be used. A single highly structured protein is selected and the amino acids in one portion of this "parental"protein are varied. In one variation, only the regions of the protein that are accessible to the surface are varied since it is these regions that are available for binding of target, while regions of the protein that are involved in maintaining its

structure are not varied. Examples of libraries created in this way include those based on structural motifs such as alpha-helices, zinc fingers, kunitz domains, and other well characterized structural motifs.

3) Human Antibody Libraries Human phage antibody libraries contain genes encoding the heavy and light chain variable regions of the antibody producing cells of human donors. These are dis- played in the phage library as antibody fragments (Fabs). The library design pref- erably includes the capability to rapidly produce and purify soluble Fabs. A first gen- eration Fab library produced by Dyax displays 37 billion distinct human antibodies.

4) Linear Peptide Libraries Linear peptide libraries may also be envisaged as being used, for example in the case where all 19 amino acids, except cysteine, at each position in a 20-mer peptide are varied to create large libraries.

Further suitable phage display libraries are the Ph. D.-7 Kit, Ph. D.-12 tu Kit or Ph. D.-C7CTM Kit, available from New England BioLabs Inc. (www. neb. com).

For further details concerning examples of phage display envisaged as suitable for use in the present invention, see for exampe Hoogenboom HR.,"Overview of antibody phage-display technology and its applications", Methods Mol Biol.

2002 ; 178: 1-37. The entire disclosure of US patents 5,837, 500,5, 821,047 and 5,702, 892 are also hereby incorporated giving information on some of the envisaged embodiments of phage display methods. Further details of techniques used to display populations of proteins and peptides and to select members with desired properties are described in Ladner RC, Ley AC,"Novel frameworks as a source of high-affinity ligands", Curr Opin Biotechnol. 2001 Aug; 12 (4): 406-10., e. g. affinity maturation has been demonstrated so that binding in the low nanomolar to subnanomolar range by non-antibodies is now achievable.

It is further envisaged that similar display methods may be used, wherein the poten- tial bioactive compounds are displayed on e. g. the outer surface of a chosen bacte- rial cell, bacterial spore or other phage type.

COSMIX Another suitable evolutionary method to generate potential bioactive compounds for use in the present invention is a COSMIX or Cosmix plexing method. Cosmix plex- ing is a technique to perform high diversity phage display thus yielding ligands with higher binding affinities than ligands evolved with conventional Ml 3 (or lambda) based phage display. This method is also envisaged as being suitable for evolving suitable bioactive species for use in the present invention.

Cosmix-plexing0 is an evolution-like process based on generating extremely high diversity followed by effective selection steps to enhance peptides, antibodies or proteins with desirable characteristics, e. g. preferably a high affinity to a bacterial toxin, antitoxin or TA complex.

The Cosmix cycle : The starting point in developing e. g. a novel peptide ligand is to choose a suitable target, e. g. a known bacterial toxin, antitoxin or TA complex. A range of requirements can also be imposed, such as specificity, and cross reactivity, affinity, pH or temperature.

An initial screen for potential bioactive compounds is done with one of Cosmix's es- tablished core libraries, which offers approximately 101° variants. This initial search results in primary ligands binding to the target. Screenings against the target are executed using phagemid display. The primary ligands are further optimized using Cosmix-plexing0 : The sequences of these ligands are totally recombined to deliver new variants with significantly improved characteristics conforming to the predefined profile. The recombination step increases the number of peptide variants that could be accessed approximately 1019 new variants. It is this extremely high degree of diversity that is accessible through Cosmix-plexing@. and allows optimization of product evolution.

In the final stage of the cycle, the optimized candidate ligands (potential bioactive compounds for use in the present invention) are selected, synthesized and their binding characteristics and physicochemical properties determined for comparison with the original specifications.

Cosmix-plexing0 may for example be applied to: Peptides : for example generating peptides consisting of 9 or 15 amino acids with nanomolar affinities.

Antibodies : for example generating antibody-like, huFab fragments with nanomolar

affinities.

Proteins Methods disclosed in US Patents Number 6, 310,191 and 6,640, 192 are also dis- closed herein by reference as being suitable embodiments of Cosmix plexing. For use in generating potential bioactive compounds.

Evolutionary methods such as those described herein may be used to generate bio- active compounds capable of binding to any of the toxins, antitoxins and TA com- plexes described herein. In all cases of evolution discussed herein, it is preferred that the potential bioactive compound binds to, or close to, an area of an antitoxin and/or toxin that intereacts with its corresponding toxin or antitoxin (i. e. a binding interface). Without being bound by theory, it is believed that this would increase the likelihood of success of identifying a suitable bioactive species as it would disrupt the binding interface between said toxin and antitoxin, preventing or reducing bind- ing and thus preventing or reducing TA complex formation, thus preventing neutral- sation of the toxin. In the most preferred embodiment of the present invention, it is preferred that the bioactive species is designed to bind one or bacterial antitoxins (preferably at one or more binding interface), such as an antitoxin from one or more of the following TA systems: parDE systems chp systems (chpA locus has also been called mazEF) higBA systems (HigB toxin, HigA antitoxin) phd/doc systems ccdAB systems (ccdA antitoxin, ccdB toxin) 'vapBC systems (also known as vagCD or STBORF1 and STBORF2) reIBE systems Computer-aided drug design In one embodiment of the present invention, it is envisaged that the bioactive spe- cies of the present invention may have been identified using a method comprising a computer-aided drug design method, more preferably a structure-based drug design method.

For example, one method envisaged as being useful for identifying a potential bioac- tive species comprises the steps of: a. employing a three-dimensional structure of a toxin, anti-toxin or toxin/antitoxin (TA) complex, or at least one sub-domain thereof b. identifying one or more potential bioactive species by designing or selecting a compound for interaction with said known three-dimensional structure.

By"sub-domain"is meant at least one complete element of secondary structure, for example an alpha helix or a beta sheet.

More specifically, a potential bioactive species for use in the present invention may be examined through the use of computer modelling, using a docking program such as GRAM, DOCK, or AUTODOCK (see Walters et al., Drug Discovery Today, Vol. 3, No. 4, (1998), 160-178, and Dunbrack et al., Folding and Design, 2, (1997), 27-42) to identify potential bioactive species. This procedure can include computer fitting of potential bioactive species to the known structure to ascertain how well the shape and the chemical structure of the potential bioactive species will bind to the toxin, antitoxin or TA complex of interest.

Also computer-assisted, manual examination of the known structure, or partly- known, structure of a toxin, antitoxin or TA complex may be performed. The use of programs such as GRID (Goodford, J. Med. Chem. , 28, (1985), 849-857) n--a pro- gram that determines probable interaction sites between molecules with various functional groups may also be used to to predict partial structures of suitable bioac- tive species.

Computer programs can be employed to estimate the attraction, repulsion, and steric hindrance of the two binding partners (e. g. the potential bioactive species and an area of a toxin, antitoxin or TA complex). Generally the tighter the fit, the fewer the steric hindrances, and the greater the attractive forces, the more potent the po- tential bioactive species, since these properties are consistent with a tighter binding constant. Furthermore, the more specificity in the design of a potential drug, the more likely it is that the drug will not interact with other proteins as well. This will

tend to minimise potential side-effects due to unwanted interactions with other pro- teins.

Alternatively, step b. may involve selecting the bioactive species by computationally screening a database of compounds for interaction with the toxin, antitoxin or TA complex of interest. For example, a 3-D descriptor for the potential bioactive species may be derived, the descriptor including geometric and functional constraints de- rived from the architecture and chemical nature of the toxin, antitoxin or TA complex.

The descriptor may then be used to interrogate the compound database, a potential bioactive species being a compound that has a good match to the features of the descriptor. In effect, the descriptor is a type of virtual pharmacophore.

Having designed or selected possible binding partners (i. e. potential bioactive spe- cies), these can then be subjected to the evaluation methods of the present inven- tion.

A computer-aided design method useful in generating suitable potential bioactive compounds may comprise the further steps of: c. obtaining or synthesising said potential bioactive species; d. forming a complex of a toxin, antitoxin or TA complex and said potential bioactive species; and e. analysing said complex by structural techniques such as NMR or X-ray crystallog- raphy to determine the ability of said potential bioactive species to interact with said toxin, antitoxin or TA complex. Detailed-structural information can then be obtained about the binding of the potential bioactive species to said toxin, antitoxin or TA complex, and in the light of this information adjustments can be made to the struc- ture or functionality of the potential bioactive species, e. g. to improve binding to the active site. Steps c. to e. may be repeated and re-repeated as necessary.

Detailed description of suitable structure-based drug design (SBDD) methods Determination of the 3D structure of a toxin, antitoxin or TA complex provides impor- tant information about the likely interaction sites. This information may then be used

for rational design of bioactive species, e. g. by computational techniques which identify possible binding ligands for the interaction sites, by enabling linked-fragment approaches to drug design, and by enabling the identification and location of bound ligands using structural techniques such as NMR or X-ray crystallographic analysis.

NMR methods Nuclear Magnetic Resonance (NMR) spectroscopy permits access to a wealth of information about the molecular recognition reaction. NMR has evolved dramatically in the last 15 years and, in parallel with the development of NMR methods for the determination of protein structure, a variety of tools aimed at detecting protein ligand interactions have been proposed and are being now used both in industrial and academic laboratories as valuable tools for structure-based drug discovery. Very recent developments have considerably increased the fraction of therapeutic targets that can be tackled by NMR and significantly reduced the amount of sample re- quired for analysis ; (for more detail on NMR techniques, see Salvatella X, Giralt E. , "NMR-based methods and strategies for drug discovery", Chem Soc Rev. 2003 Nov; 32 (6): 365-72, incorporated by reference herein).

Crystallographic methods Over the past 12 years, drugs have been developed using structure-based drug design relying upon traditional crystallographic methods. Established successes, such as the drugs designed against HIV-1 protease and neuraminidase, demon- strate the utility of a structure-based approach in the drug-discovery process.. Re- cent technological innovations such as submicroliter high-throughput crystallization, high-performance synchrotron beamlines and rapid binding-site analysis of de novo targets using virtual ligand screening and small molecule co-crystallization have resulted in a significant advance in structure-based drug discovery. Preferred X-ray crystallography methods, most preferably high-throughput methods, are described in the following articles, incorporated by reference herein: E. Abola, P. Kuhn, T. Earnest and R. C. Stevens, Automation of X-ray crystallogra- phy. Nat Struct Biol 7 (2000), pp. 973-977;

S. W. Muchmore, J. Olson, R. Jones, J. Pan, M. Blum, J. Greer, S. M. Merrick, P.

Magdalinos and V. L. Nienaber, Automated crystal mounting and data collection for protein crystallography. Struct Fold Des 8 (2000), pp. R243-R246; P. D. Adams and R. W. Grosse-Kunstleve, Recent developments in software for the automation of crystallographic macromolecular structure determination. Curr Opin Struct Biol 10 (2000), pp. 564-568; Perrakis, R. Morris and V. S. Lamzin, Automated protein model building combined with iterative structure refinement. Nat Struct Biol 6 (1999), pp. 458-463; R. C. Ste- vens, High-throughput protein crystallization. Curr Opin Struct Biol 10 (2000), pp.

558-563; Goodwill KE, Tennant MG, Stevens RC: High-throughput X-ray crystallography for structure-based drug design. Drug Discovery Today 2001, 6 (Genomics Suppl) : S113-118 ; U. Mueller, L. Nyarsik, M. Horn, H. Rauth, T. Przewieslik, W. Saenger, H. Lehrach and H. Eickhoff, Development of a technology for automation and miniaturization of protein crystallization. J Biotechnol 85 (2001), pp. 7-14.

Peter Kuhn et al.,"The genesis of high-throughput structure-based drug discovery using protein crystallography" Rowland RS, "Using X-ray crystallography in drug discovery"Curr Opin Drug Discov Devel. 2002 Jul ; 5 (4): 613-9.

Greer et al. (J. of Medicinal Chemistry, Vol. 37, (1994), 1035-1054) describes an iterative approach to ligand design based on repeated sequences of computer mod- elling, protein-ligand complex formation and X-ray analysis. Thus novel thymidylate synthase bioactive species series were designed de novo by Greer et al., and bioac- tive species may also be designed in the this way. More specifically, using e. g.

GRID on the solved 3D structure of a toxin, antitoxin or TA complex, a ligand (e. g. a potential bioactive species) may be designed that complements the known structure of a toxin, antitoxin or TA complex. The ligand can then be synthesised, formed into a complex with said toxin, antitoxin or TA complex, and said complex then analysed by X-ray crystallography to identify the actual position of the bound ligand. The structure and/or functional groups of the ligand can then be adjusted, if necessary, in view of the results of the X-ray analysis, and the synthesis and analysis sequence repeated until an optimised ligand is obtained. Related approaches to structure-

based drug design are also discussed in Bohacek et al., Medicinal Research Re- views, Vol16, (1996), 3-50.

More purely computational techniques for rational drug design may also be used to design bioactive species (for an overview of these techniques see e. g. Walters et al., Drug Discovery Today, Vol. 3, No. 4, (1998), 160-178). For example, automated ligand-receptor docking programs (discussed e. g. by Jones et al. in Current Opinion in Biotechnology, Vol. 6, (1995), 652-656) may be used to design potential bioactive species. Docking algorithms may be used to perform docking of large virtual libraries to structurally known sites and thus save on unnecessary compound screening.

Docking algorithms allow the user to search large virtual compound sets for struc- tures that have the right geometric and electronic features to fit the designated sites.

The algorithms speed up the in silico search procedure, before more extensive screening process (es) on a selected subset of actual compounds. For a more through description of flexible docking, see H. A. Carlson and J. A. McCammon, Ac- commodating protein flexibility in computational drug design. Mol Pharmacol 57 (2000), pp. 213-218Carlson and McCammon (incorporated herein by reference).

Preferably, NMR structures and/or the use of crystal structures can be used to cre- ate a composite binding site, which is more likely to find possible ligands from a da- tabase of drug-like molecules. It is well known that whole domains within a protein can move relative to one another (often a result of binding or activation) with obvious consequences for ligand binding. The challenge of docking a flexible ligand into a rigid receptor has been taken up by a number of groups; one particularly good out- come is the FlexX algorithm (see B. Kramer, M. Rarey and T. Lengauer, Evaluation of the FLEXX incremental construction algorithm for protein-ligand docking. Pro- teins 37 (1999), pp. 228-241, incorporated herein by reference) A number of scoring functions for ligand binding can be used in these methods, such as those disclosed in J. R. H. Tame, Scoring functions: a view from the bench.

J Comput Aided Mol Des 13 (1999), pp. 99-108; H. Gohlke, M. Hendlich and G.

Klebe, Knowledge-based scoring function to predict protein-ligand interactions. J Mol Biol 295 (2000), pp. 337-356 ; I. Muegge and Y. C. Martin, A general and fast scoring function for protein-ligand interactions: a simplified potential approach. J Med Chem 42 (1999), pp. 791-804; J. B. O. Mitchell, R. A. Laskowski, A. Alex and J. M. Thornton, BLEEP-potential of mean force describing protein-ligand

interactions : I. Generating potential. J Comput Chem 20 (1999), pp. 1165-1176; J. B. O. Mitchell, R. A. Laskowski, A. Alex, M. J. Forster and J. M. Thornton, BLEEP- potential of mean force describing protein-ligand interactions: Calculation of binding energies and comparison with experimental data. J Comput Chem 20 (1999), pp.

1165-1176; M. Liu and S. Wang, MCDOCK: a Monte Carlo simulation approach to the molecular docking problem. J Comput Aided Mol Des 13 (1999), pp. 435-451; J. Y. Trosset and H. A. Scheraga, Prodock: software package for protein modeling and docking. J Comput Chem 20 (1999), pp. 412-427 ; S. Makino, T. J. A. Ewing and I. D. Kuntz, DREAM++ : flexible docking program for virtual combinatorial libraries. J Comput Aided Mol Des 13 (1999), pp. 513-532; It is possible for huge numbers of drug-like candidates to be ranked by docking, for example a collaboration between Protherics and SGI (Silicon Graphics Inc.) has resulted in DockCrunch, a software/hardware system capable of scoring one million compounds in around six days (DockCrunch on World Wide Web URL: http ://www. protherics. com/crunch).

Linked-fragment approaches to drug design also require accurate information on the atomic coordinates of target receptors. The basic idea behind these approaches is to determine (computationally or experimentally) the binding locations of plural ligands to a target molecule, and then construct a molecular scaffold to connect the ligands together in such a way that their relative binding positions are preserved.

The connected ligands thus form a potential lead compound that can be further re- fined using e. g. the iterative technique of Greer et al. For a virtual linked-fragment approach see Verlinde et al., J. of Computer-Aided Molecular Design, 6, (1992), 131-147. The use of these approaches to design bioactive species is made possible by the knowledge of the structure of one or more of a toxin, antitoxin or TA complex.

Some of the techniques and approaches to structure-based drug design described above rely at some stage on X-ray analysis to identify the binding position of a ligand in a ligand-protein complex. A common way of doing this is to perform X-ray crystallography on the complex, produce a difference Fourier electron density map, and associate a particular pattern of electron density with the ligand. However, in order to produce the map (as explained e. g. by Blundell et al., in Protein Crystallog- raphy, Academic Press, New York, London and San Francisco, (1976) ) it is neces-

sary to know beforehand the protein 3D structure (or at least the protein structure factors). Therefore, determination of one or more of a toxin, antitoxin or TA complex structure also allows difference Fourier electron density maps of ligand complexes with said toxin, antitoxin or TA complex to be produced, which can greatly assist the process of rational drug design.

Virtual or computer-based screening of large chemical libraries against structural and electrostatic information of target proteins has established itself as a powerful and rapid tool for directing, or'focussing'the design of experimental libraries. A va- riety of in silico docking and scoring tools have been developed to computationally screen for favourable small molecule/protein interaction partners (see e. g. R. Abag- yan and M. Totrov, High-throughput docking for lead generation. Curr Opin Chem Biol 5 (2001), pp. 375-382 and T. L. Blundell, H. Jhoti and C. Abell, High-throughput crystallography for lead discovery in drug design. Nat Rev Drug Discov 1 (2002), pp.

45-54). Recently, the incorporation of more than one virtual ligand screening method was found to uncover more favourable drug leads (see P. S. Charifson, J. J.

Corkery, M. A. Murcko and W. P. Walters, Consensus scoring: a method for obtaining improved hit rates from docking databases of three-dimensional structures into pro- teins. J Med Chem 42 (1999), pp. 5100-5109). Additionally, virtual ligand screening methods can be validated and/or supplemented with NMR-based or X-ray crystallo- graphic-based co-complex experimental screening methods. The SAR by NMR' methodology pioneered by Fesik (see S. B. Shuker, P. J. Hajduk, R. P. Meadows and S. W. Fesik, Discovering high-affinity ligands for proteins: SAR by NMR. Science 274 (1996), pp. 1531-1534) (SAR, structure-activity relationship) provides important information for lead optimization efforts, and NMR-based binding assays are being incorporated in SBDD efforts (e. g. see triadtherapeutics. com). X-ray crystallographic screening is also being used at Abbott Laboratories (Abbott Park, IL, USA) and Astex Technology. In some cases, an integrated approach using both virtual and experimental screening and optimization can be used to identify suitable potential bioactive species.

Approaches to identify binding pockets on a target toxin, antitoxin or TA complex may also be used to aid design of suitable bioactive compounds: these techniques include geometric analyses of protein surfaces, comparisons of protein structures, similarity searches in databases of protein cavities, and docking scans to reveal

areas of high ligand complementarity. In the context of binding-site analysis, powerful data mining tools help to retrieve experimental information about related protein-ligand complexes. To identify interaction hot spots, various potential functions and knowledge-based approaches are available for mapping binding regions. The results may subsequently be used to guide virtual screenings for new ligands via pharmacophore searches or docking simulations (for more information on these methods, see Sotriffer C, Klebe G,"Identification and mapping of small- molecule binding sites in proteins: computational tools for structure-based drug design", Farmaco. 2002 Mar ; 57 (3): 243-51, incorporated herein by reference.) Other approaches to computer-aided bioactive molecule design A first stage of a drug design program may involve computer-based in silico screen- ing of compound databases (such as the Cambridge Structural Database) with the aim of identifying compounds which interact with a site or sites of the target bio- molecule. Screening selection criteria may be based on pharmacokinetic properties such as metabolic stability and toxicity. However, determination of at least part of the structure of a toxin, antitoxin or TA complex allows the architecture and chemical nature of each toxin, antitoxin or TA complex to be identified, which in turn allows the geometric and functional constraints of a descriptor for the potential bioactive species to be derived. The descriptor is, therefore, a type of virtual 3-D pharma- cophore, which can also be used as selection criteria or filter for database screen- ing.

Bioactive molecules may also be selected using a method based on generation and selection of molecular diversity, i. e. a so-called"Darwinian"method, i. e. a method different from the structure-based, structure-modulation approaches described above. An example of a Darwinian method is inverse QSAR. It consists of the com- putational generation of candidate chemical structures and their selection according to a previously established QSAR model. New trends in the field of combinatorial chemical syntheses comprise the concepts of virtual combinatorial synthesis and virtual or computational screening. Virtual combinatorial synthesis, closely related to inverse QSAR, can be defined as the computational simulation of the generation of new chemical structures by using a combinatorial strategy to generate a virtual li- brary. Virtual screening is the selection of chemical structures having potential de- sirable properties from a database or virtual library in order to be synthesized and

assayed. For more information on these methods as envisaged for use in the meth- ods of the present invention, see de Julian-Ortiz JV,"Virtual darwinian drug design: QSAR inverse problem, virtual combinatorial chemistry, and computational screen- ing". Comb Chem High Throughput Screen. 2001 May; 4 (3) : 295-310, incorporated herein by reference.

Various QSAR predictive methods have been developed to help direct the synthesis and screening process, for example as disclosed in the following references, incor- porated herein by reference : D. Barnum et al., Identification of Common Functional Configuration Among Mole- cules. J. Chem, Inf. Comput. Sci. 36 (1996), pp. 563-571.

J. Greene et al., Chemical Function Queries for 3D Database Search. J. Chem. Inf.

Comput Sci. 34 (1994), pp. 1297-1308.

R. D. Cramer, III et a/., Comparative Molecular Field Analysis (CoMFA), Effect of Shape on Binding of Steroids to Carrier Proteins. J. Am. Chem. Soc. 110 (1998), pp.

5959-5967.

M. J. McGregor and S. M. Muskal, Pharmacophore Fingerprinting. Application to QSAR and Focused Library Design. J. Chem. Inf. Comput. Sci. 39 (1999), pp. 569- 574.

H. Matter, Selecting Optimally Diverse Compounds from Structure Databases: A Validation Study of Two-Dimensional and Three-Dimensional Molecular Descriptors.

J. Med. Chem. 40 (1997), p. 1219.

H. J. Bohm and M. Stahl, Structure-Based Library Design: Molecular Modelling Merges with Combinatorial Chemistry. Curr Opin Chem Biol 4 (2000), pp. 283-286.

D. Joseph-McCarthy, Computational Approaches to Structure-Based Ligand Design.

Pharmacol Ther 84 (1999), pp. 179-191.

The Woolford algorithm, described in US Patent 6,226, 603, may also be used to predict preferred bioactive species binding targets in one or more of a toxin, anti- toxin or TA complex.

Other references disclosing suitable computer-based drug design methods for gen- erating potential bioactive species for use in the present invention include (incorpo- rated herein by reference): Waszkowycz B, "Structure-based approaches to drug design and virtual screening"

Curr Opin Drug Discov Devel. 2002 May ; 5 (3): 407-13.

Barry A. Bunin,"Increasing the efficiency of small-molecule drug discovery"DDT Vol. 8, No 18 September 2003.

Maulik et al., 1997, Molecular Biotechnology: Therapeutic Applications and Strate- gies, Wiley-Liss, Inc Lee A, Breitenbucher JG, "The impact of combinatorial chemistry on drug discov- ery". Curr Opin Drug Discov Devel. 2003 Jul ; 6 (4): 494-508.

Veselovsky AV, Ivanov AS, "Strategy of computer-aided drug design", Curr Drug Targets Infect Disord. 2003 Mar; 3 (1) : 33-40.

Paul J Gane and Philip M Dean-"Recent advances in structure-based rational drug design"Current Opinion in Structural Biology, Volume 10, Issue 4,1 August 2000, Pages 401-404 Klebe G, "Recent developments in structure-based drug design", J Mol Med.

2000; 78 (5): 269-81.

J. Antel, Integration of combinatorial chemistry and structure based drug design.

Curr Opin Drug Discov Dev 2 (1999), pp. 224-233.

Suitable structures and models useful for structure based drug design to generate potential bioactive compounds are any complete or partial structures of the toxins, antitoxins or TA complexes described herein. In all cases of structure-based drug design discussed herein, it is preferred that the bioactive species is designed to bind to, or close to, an area of an antitoxin and/or toxin that intereacts with its corre- sponding toxin or antitoxin. Without being bound by theory, it is believed that this would increase the likelihood of success of identifying a suitable bioactive species as it would disrupt the binding interface between said toxin and antitoxin, thus reduc- ing or preventing TA complex formation, thus preventing neutralisation of the toxin.

In the most preferred embodiment of the present invention, it is preferred that the bioactive species is designed to bind a TA complex, such as a TA complex of one or more of the following TA systems: parDE systems chop systems (chpA locus has also been called mazEF) higBA systems (HigB toxin, HigA antitoxin) phdldoc systems 'ccdAB systems (ccdA antitoxin, ccdB toxin)

vapBC systems (also known as vagCD or STBORF1 and STBORF2) ReIBE systems Most preferably, the complex is a ReIBE protein complex or, most preferably, the MazEF protein complex, the structure of which is disclosed in Kamada, K et al., Crystal Structure of the Maze/Mazf Complex. Molecular Bases of Antidote-Toxin Recognition Mol. Cell 11 pp. 875 (2003).

Preferred structures for use in a method of structure based drug design may also include molecular models produced by those of skill in the art, including models produced by any suitable molecular modeling method, such as molecular replace- ment and fold recognition-related methods.

Administration forms The main routes of bioactive substance delivery in the treatment methods of the present invention are intravenous, oral, and topical, as will be described below.

Other drug-administration methods, such as subcutaneous injection or via inhala- tion, which are effective to deliver the drug to a target site or to introduce the drug into the bloodstream, are also contemplated.

One area to which the pharmaceutical preparation of the invention is administered may be any mucosal membrane of the individual to which the biologically active substance is to be given, e. g. in the nose, vagina, eye, mouth, genital tract, lungs, gastrointestinal tract, or rectum, preferably the mucosa of the nose, mouth or va- gina.

The bioactive substances of the invention may be administered parenterally, that is by intravenous, intramuscular, subcutaneous intranasal, intrarectal, intravaginal or intraperitoneal administration. The subcutaneous and intramuscular forms of par- enteral administration are generally preferred. Appropriate dosage forms for such administration may be prepared by conventional techniques. The bioactive species may also be administered by inhalation, that is by intranasal and oral inhalation ad- ministration. Appropriate dosage forms for such administration, such as an aerosol formulation or a metered dose inhaler, may be prepared by conventional techniques.

The bioactive substances according to the invention may be administered with at least one other compound, such as another bioactive species of the present inven- tion or another anti-microbial compound. By"administered with"is meant that the compounds may be administered simultaneously, either as separate formulations or combined in a unit dosage form, or administered sequentially.

Dosing regimes The dosage requirements will vary with the particular drug composition employed, the route of administration and the particular subject being treated. Ideally, an indi- vidual to be treated by the present method will receive a pharmaceutically effective amount of the bioactive substances in the maximum tolerated dose, generally no higher than that required before drug resistance develops.

For all methods of use disclosed herein for the bioactive substances, the daily oral dosage regimen will preferably be from about 0.01 to about 80 mg/kg of total body weight. The daily parenteral dosage regimen about 0.001 to about 80 mg/kg of total body weight. The daily topical dosage regimen will preferably be from 0.1 mg to 150 mg, administered one to four, preferably two or three times daily, thus it is preferred that the contacting of said microbial cell with a bioactive species as described herein is performed 1-4 times daily, such as 2-3 times daily or once daily.

The daily inhalation dosage regimen will preferably be from about 0.01 mg/kg to about 1 mg/kg per day. It will also be recognized by one of skill in the art that the optimal quantity and spacing of individual dosages of a bioactive species or a phar- maceutically acceptable salt thereof will be determined by the nature and extent of the condition being treated, the form, route and site of administration, and the par- ticular patient being treated, and that such optimums can be determined by conven- tional techniques. It will also be appreciated by one of skill in the art that the optimal course of treatment, i. e. , the number of doses of a bioactive species or a pharma- ceutically acceptable salt thereof given per day for a defined number of days, can be ascertained by those skilled in the art using conventional course of treatment deter- mination tests.

The term"unit dosage form"as used herein refers to physically discrete units suit- able as unitary dosages for human and animal subjects, each unit containing a pre-

determined quantity of a bioactive substance, alone or in combination with other agents, calculated in an amount sufficient to produce the desired effect in associa- tion with a pharmaceutical acceptable diluent, carrier, or vehicle. The specifica- tions for the unit dosage forms of the present invention depend on the particular bioactive substance or bioactive species employed and the effect to be achieved, as well as the pharmacodynamics associated with each bioactive substances in the individual. The dose administered should be an"effective amount"or an amount necessary to achieve an"effective level"in the individual patient.

Since the"effective level"is used as the preferred endpoint for dosing, the actual dose and schedule can vary, depending on interindividual differences in pharma- cokinetics, drug distribution, and metabolism. The"effective level"can be defined, for example, as the blood or tissue level desired in the patient that corresponds to a concentration of one or more bioactive species according to the invention.

Pharmaceutical compositions containing a bioactive substance of the present inven- tion may be prepared by conventional techniques, e. g. as described in Remington: The Science and Practice of Pharmacy 1995, edited by E. W. Martin, Mack Publish- ing Company, 19th edition, Easton, Pa. The compositions may appear in conven- tional forms, for example capsules, tablets, aerosols, solutions, suspensions or topi- cal applications.

Formulations Whilst it is possible for the bioactive substances, or salts thereof, of the present in- vention to be administered as the raw chemical, it is preferred to present them in the form of a pharmaceutical formulation. Accordingly, the present invention further pro- vides a pharmaceutical formulation, for medicinal application, which comprises a bioactive species of the present invention or a pharmaceutically acceptable salt thereof, as herein defined, and a pharmaceutical acceptable carrier therefor.

The bioactive substances of the present invention may be formulated in a wide vari- ety of oral administration dosage forms. The pharmaceutical compositions and dos- age forms may comprise the bioactive substances of the invention or pharmaceuti- cally acceptable salts or a crystal form thereof as the active component. The phar- maceutically acceptable carriers can be either solid or liquid. Solid form preparations

include powders, tablets, pills, capsules, cachets, suppositories, and dispersible granules. A solid carrier can be one or more substances which may also act as dilu- ents, flavoring agents, solubilizers, lubricants, suspending agents, binders, pre- servatives, wetting agents, tablet disintegrating agents, or an encapsulating mate- rial.

Preferably, the composition will be about 0.5% to 75% by weight of a bioactive sub- stance or bioactive substances of the invention, with the remainder consisting of suitable pharmaceutical excipients. For oral administration, such excipients include pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, talcum, cellulose, glucose, gelatin, sucrose, magnesium carbonate, and the like.

In powders, the carrier is a finely divided solid which is a mixture with the finely di- vided active component. In tablets, the active component is mixed with the carrier having the necessary binding capacity in suitable proportions and compacted in the shape and size desired. The powders and tablets preferably containing from one to about seventy percent of the active bioactive species. Suitable carriers are magne- sium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, a low melting wax, cocoa butter, and the like. The term"preparation"is intended to include the formulation of the active bioactive species with encapsulating material as carrier providing a capsule in which the active component, with or without carriers, is sur- rounded by a carrier, which is in association with it. Similarly, cachets and lozenges are included. Tablets, powders, capsules, pills, cachets, and lozenges can be as solid forms suitable for oral administration.

Drops according to the present invention may comprise sterile or non-sterile aque- ous or oil solutions or suspensions, and may be prepared by dissolving the bioactive species in a suitable aqueous solution, optionally including a bactericidal and/or fungicidal agent and/or any other suitable preservative, and optionally including a surface active agent. The resulting solution may then be clarified by filtration, transferred to a suitable container which is then sealed and sterilized by autoclaving or maintaining at 98-100 °C for half an hour. Alternatively, the solution may be steril- ized by filtration and transferred to the container aseptically. Examples of bacteri-

cidal and fungicidal agents suitable for inclusion in the drops are phenylmercuric nitrate or acetate (0.002%), benzalkonium chloride (0. 01 %) and chlorhexidine ace- tate (0.01 %). Suitable solvents for the preparation of an oily solution include glyc- erol, diluted alcohol and propylene glycol.

Also included are solid form preparations which are intended to be converted, shortly before use, to liquid form preparations for oral administration. Such liquid forms include solutions, suspensions, and emulsions. These preparations may con- tain, in addition to the active component, colorants, flavors, stabilizers, buffers, artifi- cial and natural sweeteners, dispersants, thickeners, solubilizing agents, and the like.

Other forms suitable for oral administration include liquid form preparations including emulsions, syrups, elixirs, aqueous solutions, aqueous suspensions, toothpaste, gel dentrifrice, chewing gum, or solid form preparations which are intended to be con- verted shortly before use to liquid form preparations. Emulsions may be prepared in solutions in aqueous propylene glycol solutions or may contain emulsifying agents such as lecithin, sorbitan monooleate, or acacia. Aqueous solutions can be prepared by dissolving the active component in water and adding suitable colorants, flavors, stabilizing and thickening agents. Aqueous suspensions can be prepared by dis- persing the finely divided active component in water with viscous material, such as natural or synthetic gums, resins, methylcellulose, sodium carboxymethylcellulose, and other well known suspending agents. Solid form preparations include solutions, suspensions, and emulsions, and may contain, in addition to the active component, colorants, flavors, stabilizers, buffers, artificial and natural sweeteners, dispersants, thickeners, solubilizing agents, and the like.

The bioactive substances of the present invention may be formulated for parenteral administration (e. g. , by injection, for example bolus injection or continuous infusion) and may be presented in unit dose form in ampoules, pre-filled syringes, small vol- ume infusion or in multi-dose containers with an added preservative. The composi- tions may take such forms as suspensions, solutions, or emulsions in oily or aque- ous vehicles, for example solutions in aqueous polyethylene glycol. Examples of oily or nonaqueous carriers, diluents, solvents or vehicles include propylene glycol, polyethylene glycol, vegetable oils (e. g., olive oil), and injectable organic esters

(e. g., ethyl oleat), and may contain formulatory agents such as preserving, wetting, emulsifying or suspending, stabilizing and/or dispersing agents. Alternatively, the bioactive species may be in powder form, obtained by aseptic isolation of sterile solid or by lyophilisation from solution for constitution before use with a suitable ve- hicle, e. g., sterile, pyrogen-free water.

Oils useful in parenteral formulations include petroleum, animal, vegetable, or syn- thetic oils. Specific examples of oils useful in such formulations include peanut, soy- bean, sesame, cottonseed, corn, olive, petrolatum, and mineral. Suitable fatty acids for use in parenteral formulations include oleic acid, stearic acid, and isostearic acid.

Ethyl oleate and isopropyl myristate are examples of suitable fatty acid esters.

Suitable soaps for use in parenteral formulations include fatty alkali metal, ammo- nium, and triethanolamine salts, and suitable detergents include (a) cationic deter- gents such as, for example, dimethyl dialkyl ammonium halides, and alkyl pyridinium halides ; (b) anionic detergents such as, for example, alkyl, aryl, and olefin sul- fonates, alkyl, olefin, ether, and monoglyceride sulfates, and sulfosuccinates, (c) nonionic detergents such as, for example, fatty amine oxides, fatty acid alkanola- mides, and polyoxyethylenepolypropylene copolymers, (d) amphoteric detergents such as, for example, alkyl-. beta. -aminopropionates, and 2-alkyl-imidazoline quater- nary ammonium salts, and (e) mixtures thereof.

The parenteral formulations typically will contain from about 0.5 to about 25% by weight of the bioactive species in solution. Preservatives and buffers may be used.

In order to minimize or eliminate irritation at the site of injection, such compositions may contain one or more nonionic surfactants having a hydrophile-lipophile balance (HLB) of from about 12 to about 17. The quantity of surfactant in such formulations will typically range from about 5to about 15% by weight. Suitable surfactants include polyethylene sorbitan fatty acid esters, such as sorbitan monooleate and the high molecular weight adducts of ethylene oxide with a hydrophobic base, formed by the condensation of propylene oxide with propylene glycol. The parenteral formulations can be presented in unit-dose or multi-dose sealed containers, such as ampules and vials, and can be stored in a freeze-dried (lyophilized) condition requiring only the addition of the sterile liquid excipient, for example, water, for injections, immediately

prior to use. Extemporaneous injection solutions and suspensions can be prepared from sterile powders, granules, and tablets of the kind previously described.

The bioactive substances of the invention can also be delivered topically. Regions for topical administration include the skin surface and also mucous membrane tis- sues of the vagina, rectum, nose, mouth, and throat. Compositions for topical ad- ministration via the skin and mucous membranes should not give rise to signs of irritation, such as swelling or redness.

The topical composition may include a pharmaceutical acceptable carrier adapted for topical administration. Thus, the composition may take the form of a suspension, solution, ointment, lotion, sexual lubricant, cream, foam, aerosol, spray, suppository, implant, inhalant, tablet, capsule, dry powder, syrup, balm or lozenge, for example.

Methods for preparing such compositions are well known in the pharmaceutical in- dustry.

The bioactive substances of the present invention may be formulated for topical ad- ministration to the epidermis as ointments, creams or lotions, or as a transdermal patch. Ointments and creams may, for example, be formulated with an aqueous or oily base with the addition of suitable thickening and/or gelling agents. Lotions may be formulated with an aqueous or oily base and will in general also containing one or more emulsifying agents, stabilizing agents, dispersing agents, suspending agents, thickening agents, or coloring agents. Formulations suitable for topical ad- ministration in the mouth include lozenges comprising active agents in a flavored base, usually sucrose and acacia or tragacanth; pastilles comprising the bioactive species in an inert base such as gelatin and glycerin or sucrose and acacia; and mouthwashes comprising the bioactive species in a suitable liquid carrier.

Creams, ointments or pastes according to the present invention are semi-solid for- mulations of the bioactive species for external application. They may be made by mixing the bioactive species in finely-divided or powdered form, alone or in solution or suspension in an aqueous or non-aqueous fluid, with the aid of suitable machin- ery, with a greasy or non-greasy base. The base may comprise hydrocarbons such as hard, soft or liquid paraffin, glycerol, beeswax, a metallic soap; a mucilage ; an oil of natural origin such as almond, corn, arachis, castor or olive oil ; wool fat or its de-

rivatives or a fatty acid such as steric or oleic acid together with an alcohol such as propylene glycol or a macrogel. The formulation may incorporate any suitable sur- face active agent such as an anionic, cationic or non-ionic surfactant such as a sor- bitan ester or a polyoxyethylene derivative thereof. Suspending agents such as natural gums, cellulose derivatives or inorganic materials such as silicaceous silicas, and other ingredients such as lanolin, may also be included.

Lotions according to the present invention include those suitable for application to the skin or eye. An eye lotion may comprise a sterile aqueous solution optionally containing a bactericide and may be prepared by methods similar to those for the preparation of drops. Lotions or liniments for application to the skin may also include an agent to hasten drying and to cool the skin, such as an alcohol or acetone, and/or a moisturizer such as glycerol or an oil such as castor oil or arachis oil.

The bioactive substances described herein can be administered transdermally.

Transdermal administration typically involves the delivery of a pharmaceutical agent for percutaneous passage of the drug into the systemic circulation of the patient.

The skin sites include anatomic regions for transdermally administering the drug and include the forearm, abdomen, chest, back, buttock, mastoidal area, and the like.

Transdermal delivery is accomplished by exposing a source of the complex to a patient's skin for an extended period of time. Transdermal patches have the added advantage of providing controlled delivery of a bioactive substances to the body.

See Transdermal Drug Delivery: Developmental Issues and Research Initiatives, Hadgraft and Guy (eds.), Marcel Dekker, Inc., (1989); Controlled Drug Delivery: Fundamentals and Applications, Robinson and Lee (eds.), Marcel Dekker Inc., (1987) ; and Transdermal Delivery of Drugs, Vols. 1-3, Kydonieus and Berner (eds.), CRC Press, (1987). Such dosage forms can be made by dissolving, dispersing, or otherwise incorporating the pharmaceutical agent-chemical modifier complex in a proper medium, such as an elastomeric matrix material. Absorption enhancers can also be used to increase the flux of the bioactive species across the skin. The rate of such flux can be controlled by either providing a rate-controlling membrane or dis- persing the bioactive species in a polymer matrix or gel.

A variety of types of transdermal patches will find use in the methods described herein. For example, a simple adhesive patch can be prepared from a backing ma- terial and an acrylate adhesive. The bioactive substance is formulated into the ad- hesive casting solution and allowed to mix thoroughly. The solution is cast directly onto the backing material and the casting solvent is evaporated in an oven, leaving an adhesive film. The release liner can be attached to complete the system.

Alternatively, a polyurethane matrix patch can be employed to deliver the pharma- ceutical agent-chemical modifier complex. The layers of this patch comprise a back- ing, a polyurethane drug/enhancer matrix, a membrane, an adhesive, and a release liner. The polyurethane matrix is prepared using a room temperature curing polyure- thane prepolymer. Addition of water, alcohol, and complex to the prepolymer results in the formation of a tacky firm elastomer that can be directly cast only the backing material.

A further embodiment of this invention will utilize a hydrogel matrix patch. Typically, the hydrogel matrix will comprise alcohol, water, drug, and several hydrophilic poly- mers. This hydrogel matrix can be incorporated into a transdermal patch between the backing and the adhesive layer.

The liquid reservoir patch will also find use in the methods described herein. This patch comprises an impermeable or semipermeable, heat salable backing material, a heat salable membrane, an acrylate based pressure sensitive skin adhesive, and a siliconized release liner. The backing is heat sealed to the membrane to form a reservoir which can then be filled with a solution of the complex, enhancers, gelling agent, and other excipients.

Foam matrix patches are similar in design and components to the liquid reservoir system, except that the gelled pharmaceutical agent-chemical modifier solution is constrained in a thin foam layer, typically a polyurethane. This foam layer is situated between the backing and the membrane which have been heat sealed at the pe- riphery of the patch.

For passive delivery systems, the rate of release is typically controlled by a mem- brane placed between the reservoir and the skin, by diffusion from a monolithic de-

vice, or by the skin itself serving as a rate-controlling barrier in the delivery system.

See U. S. Pat. Nos. 4,816, 258; 4,927, 408; 4,904, 475; 4,588, 580,4, 788,062 ; and the like. The rate of drug delivery will be dependent, in part, upon the nature of the membrane. For example, the rate of drug delivery across membranes within the body is generally higher than across dermal barriers. The rate at which the complex is delivered from the device to the membrane is most advantageously controlled by the use of rate-limiting membranes which are placed between the reservoir and the skin. Assuming that the skin is sufficiently permeable to the complex (i. e. , absorption through the skin is greater than the rate of passage through the membrane), the membrane will serve to control the dosage rate experienced by the patient.

Suitable permeable membrane materials may be selected based on the desired degree of permeability, the nature of the complex, and the mechanical considera- tions related to constructing the device. Exemplary permeable membrane materials include a wide variety of natural and synthetic polymers, such as polydimethylsilox- anes (silicone rubbers), ethylenevinylacetate copolymer (EVA), polyurethanes, poly- urethane-polyether copolymers, polyethylenes, polyamides, polyvinylchlorides (PVC), polypropylenes, polycarbonates, polytetrafluoroethylenes (PTFE), cellulosic materials, e. g., cellulose triacetate and cellulose nitrate/acetate, and hydrogels, e. g., 2-hydroxyethylmethacrylate (HEMA).

Other items may be contained in the device, such as other conventional compo- nents of therapeutic products, depending upon the desired device characteristics.

For example, the compositions according to this invention may also include one or more preservatives or bacteriostatic agents, e. g., methyl hydroxybenzoate, propyl hydroxybenzoate, chlorocresol, benzalkonium chlorides, and the like. These phar- maceutical compositions also can contain other active ingredients such as antim- icrobial agents, particularly antibiotics, anesthetics, analgesics, and antipruritic agents.

The bioactive substances of the present invention may be formulated for administra- tion as suppositories. A low melting wax, such as a mixture of fatty acid glycerides or cocoa butter is first melted and the active component is dispersed homogene- ously, for example, by stirring. The molten homogeneous mixture is then poured into convenient sized molds, allowed to cool, and to solidify.

The bioactive substance may be formulated into a suppository comprising, for ex- ample, about 0.5% to about 50% of a bioactive species of the invention, disposed in a polyethylene glycol (PEG) carrier (e. g. , PEG 1000 [96%] and PEG 4000 [4%].

The bioactive substances of the present invention may be formulated for vaginal administration. Pessaries, tampons, creams, gels, pastes, foams or sprays contain- ing in addition to the bioactive species such carriers as are known in the art to be appropriate.

The bioactive substances of the present invention may be formulated for nasal ad- ministration. The solutions or suspensions are applied directly to the nasal cavity by conventional means, for example with a dropper, pipette or spray. The formulations may be provided in a single or multidose form. In the latter case of a dropper or pi- pette this may be achieved by the patient administering an appropriate, predeter- mined volume of the solution or suspension. In the case of a spray this may be achieved for example by means of a metering atomizing spray pump.

The bioactive substances of the present invention may be formulated for aerosol administration, particularly to the respiratory tract and including intranasal admini- stration. The bioactive species will generally have a small particle size for example of the order of 5 microns or less. Such a particle size may be obtained by means known in the art, for example by micronization. The bioactive species is provided in a pressurized pack with a suitable propellant such as a chlorofluorocarbon (CFC) for example dichlorodifluoromethane, trichlorofluoromethane, or dichlorotetrafluoro- ethane, carbon dioxide or other suitable gas. The aerosol may conveniently also contain a surfactant such as lecithin. The dose of drug may be controlled by a me- tered valve. Alternatively the bioactive species may be provided in a form of a dry powder, for example a powder mix of the bioactive species in a suitable powder base such as lactose, starch, starch derivatives such as hydroxypropylmethyl cellu- lose and polyvinylpyrrolidine (PVP). The powder carrier will form a gel in the nasal cavity. The powder composition may be presented in unit dose form for example in capsules or cartridges of e. g. , gelatin or blister packs from which the powder may be administered by means of an inhaler.

When desired, formulations can be prepared with enteric coatings adapted for sus- tained or controlled release administration of the bioactive species.

The pharmaceutical preparations are preferably in unit dosage forms. In such form, the preparation is subdivided into unit doses containing appropriate quantities of the active component. The unit dosage form can be a packaged preparation, the pack- age containing discrete quantities of preparation, such as packeted tablets, cap- sules, and powders in vials or ampoules. Also, the unit dosage form can be a cap- sule, tablet, cachet, or lozenge itself, or it can be the appropriate number of any of these in packaged form.

Pharmaceutical acceptable salts Pharmaceutical acceptable salts of the instant bioactive substances, where they can be prepared, are also intended to be covered by this invention. These salts will be ones which are acceptable in their application to a pharmaceutical use. By that it is meant that the salt will retain the biological activity of the parent bioactive species and the salt will not have untoward or deleterious effects in its application and use in treating diseases.

Pharmaceutically acceptable salts are prepared in a standard manner. If the parent bioactive species is a base it is treated with an excess of an organic or inorganic acid in a suitable solvent. If the parent bioactive species is an acid, it is treated with an inorganic or organic base in a suitable solvent.

The bioactive substances of the invention may be administered in the form of an alkali metal or earth alkali metal salt thereof, concurrently, simultaneously, or to- gether with a pharmaceutical acceptable carrier or diluent, especially and prefera- bly in the form of a pharmaceutical composition thereof, whether by oral, rectal, or parenteral (including subcutaneous) route, in an effective amount.

Examples of pharmaceutically acceptable acid addition salts for use in the present inventive pharmaceutical composition include those derived from mineral acids, such as hydrochloric, hydrobromic, phosphoric, metaphosphoric, nitric and sulfuric acids, and organic acids, such as tartaric, acetic, citric, malic, lactic, fumaric, ben-

zoic, glycolic, gluconic, succinic, p-toluenesulphonic acids, and arylsulphonic, for example.

Examples of a typical tablet A typical tablet which may be prepared by conventional tabletting techniques may contain: Core: bioactive substance (as free bioactive species or salt thereof) 100 mg Colloidal silicon dioxide (Aerosil) 1.5 mg Cellulose, microcryst. (Avicel) 70 mg Modified cellulose gum (Ac-Di-Sol) 7.5 mg Magnesium stearate Coating: HPMC approx. 9 mg *Mywacett 9-40 T approx.

0.9 mg *Acylated monoglyceride used as plasticizer for film coating.

The pharmaceutical carrier Illustrative solid carriers include lactose, terra alba, sucrose, talc, gelatin, agar, pec- tin, acacia, magnesium stearate, stearic acid and the like. A solid carrier can include one or more substances which may also act as flavoring agents, lubricants, solubi- lizers, suspending agents, fillers, glidants, compression aids, binders or tablet-

disintegrating agents; it can also be an encapsulating material. In powders, the car- rier is a finely divided solid which is in admixture with the finely divided bioactive species. In tablets, the bioactive substance is mixed with a carrier having the neces- sary compression properties in suitable proportions, and compacted in the shape and size desired. The powders and tablets preferably contain up to 99% of the bio- active species. Suitable solid carriers include, for example, calcium phosphate, magnesium stearate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, methyl cellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidine, low melting waxes and ion exchange resins.

Illustrative liquid carriers include syrup, peanut oil, olive oil, water, etc. Liquid carri- ers are used in preparing solutions, suspensions, emulsions, syrups, elixirs and pressurized compositions. The bioactive substance can be dissolved or suspended in a pharmaceutical acceptable liquid carrier such as water, an organic solvent, a mixture of both or pharmaceutically acceptable oils or fats. The liquid carrier can contain other suitable pharmaceutical additives such as solubilizers, emulsifiers, buffers, preservatives, sweeteners, flavoring agents, suspending agents, thickening agents, colors, viscosity regulators, stabilizers or osmo-regulators. Suitable exam- ples of liquid carriers for oral and parenteral administration include water (partially containing additives as above, e. g. cellulose derivatives, preferably sodium car- oxymethyl cellulose solution), alcohols (including monohydric alcohols and polyhy- dric alcohols, e. g. glycols) and their derivatives, and oils (e. g. fractionated coconut oil and arachis oil). For parenteral administration, the carrier can also be an oily es- ter such as ethyl oleate and isopropyl myristate. Sterile liquid carders are useful in sterile liquid form compositions for parenteral administration. The liquid carrier for pressurized compositions can be halogenated hydrocarbon or other pharmaceuti- cally acceptable propellant. Liquid pharmaceutical compositions which are sterile solutions or suspensions can be utilized by, for example, intramuscular, intraperito- neal or subcutaneous injection. Sterile solutions can also be administered intrave- nously. The bioactive species can also be administered orally either in liquid or solid composition form.

The carrier or excipient may include time delay material well known to the art, such as glyceryl monostearate or glyceryl distearate along or with a wax, ethylcellulose, hydroxypropylmethylcellulose, methylmethacrylate and the like. When formulated for

oral administration, 0. 01 % Tween 80 in PHOSAL PG-50 (phospholipid concentrate with 1, 2-propylene glycol, A. Nattermann & Cie. GmbH) has been recognized as providing an acceptable oral formulation for other compounds, and may be adapted to formulations for various bioactive species of this invention.

"Pharmaceutical agent or drug"refers to any chemical or biological material, com- pound, or composition capable of inducing a desired therapeutic effect when prop- erly administered to a patient. Some drugs are sold in an inactive form that is con- verted in vivo into a metabolite with pharmaceutical activity. For purposes of the present invention, the terms"pharmaceutical agent"and"drug"encompass both the inactive drug and the active metabolite.

"Transport"and"delivery"refers to the passage of a substance across or through the skin (i. e., transdermal), including the epidermis and dermis, or across a mucosal membrane (i. e., gastrointestinal, sublingual, buccal, nasal, pulmonary, vaginal, cor- neal, and ocular membranes), where the substance can contact, and be absorbed into, the capillaries. In certain instances, the delivery and/or transport of the sub- stance across other membranes will be effected.

"Penetration enhancer"refers to a substance which is used to increase the trans- dermal or transmembrane flux of a bioactive species. A penetration enhancer is typically applied to the skin or mucous membrane in combination with the bioactive species. Enhancers are believed to function by disrupting the skin or mucous mem- brane barrier or changing the partitioning behavior of the drug in the skin or mucous membrane.

Controlled release formulations The following terms may be considered to be substantially equivalent to controlled release, for the purposes of the present invention: continuous release, controlled release, delayed release, depot, gradual release, long-term release, programmed release, prolonged release, proportionate release, protracted release, repository, retard, slow release, spaced release, sustained release, time coat, timed release, delayed action, extended action, layered-time action, long acting, prolonged action, repeated action, slowing acting, sustained action, sustained-action medications, and

extended release. Further discussions of these terms may be found in Lesczek Krowczynski, Extended-Release Dosage Forms, 1987 (CRC Press, Inc.).

The various controlled release technologies cover a very broad spectrum of drug dosage forms. Controlled release technologies include, but are not limited to physi- cal systems and chemical systems.

Physical systems include, but are not limited to, reservoir systems with rate- controlling membranes, such as microencapsulation, macroencapsulation, and membrane systems; reservoir systems without rate-controlling membranes, such as hollow fibers, ultra microporous cellulose triacetate, and porous polymeric sub- strates and foams; monolithic systems, including those systems physically dissolved in non-porous, polymeric, or elastomeric matrices (e. g., non-erodible, erodible, envi- ronmental agent ingression, and degradable), and materials physically dispersed in non-porous, polymeric, or elastomeric matrices (e. g., non-erodible, erodible, envi- ronmental agent ingression, and degradable) ; laminated structures, including reser- voir layers chemically similar or dissimilar to outer control layers; and other physical methods, such as osmotic pumps, or adsorption onto ion-exchange resins.

Chemical systems include, but are not limited to, chemical erosion of polymer matri- ces (e. g. , heterogeneous, or homogeneous erosion), or biological erosion of a poly- mer matrix (e. g. , heterogeneous, or homogeneous). Additional discussion of catego- ries of systems for controlled release may be found in Agis F. Kydonieus, Controlled Release Technologies : Methods, Theory and Applications, 1980 (CRC Press, Inc.).

Controlled release drug delivery systems may also be categorized under their basic technology areas, including, but not limited to, rate-preprogrammed drug delivery systems, activation-modulated drug delivery systems, feedback-regulated drug de- livery systems, and site-targeting drug delivery systems.

In rate-preprogrammed drug delivery systems, release of drug molecules from the delivery systems"preprogrammed"at specific rate profiles. This may be accom- plished by system design, which controls the molecular diffusion of drug molecules in and/or across the barrier medium within or surrounding the delivery system. Fick's laws of diffusion are often followed.

In activation-modulated drug delivery systems, release of drug molecules from the delivery systems is activated by some physical, chemical or biochemical processes and/or facilitated by the energy supplied externally. The rate of drug release is then controlled by regulating the process applied, or energy input.

In feedback-regulated drug delivery systems, release of drug molecules from the delivery systems may be activated by a triggering event, such as a biochemical sub- stance, in the body. The rate of drug release is then controlled by the concentration of triggering agent detected by a sensor in the feedback regulated mechanism.

In a site-targeting controlled-release drug delivery system, the drug delivery system targets the active molecule to a specific site or target tissue or cell. This may be ac- complished, for example, by a conjugate including a site specific targeting moiety that leads the drug delivery system to the vicinity of a target tissue (or cell), a solubi- lizer that enables the drug delivery system to be transported to and preferentially taken up by a target tissue, and a drug moiety that is covalently bonded to the poly- mer backbone through a spacer and contains a cleavable group that can be cleaved only by a specific enzyme at the target tissue.

While a preferable mode of controlled release drug delivery will be oral, other modes of delivery of controlled release compositions according to this invention may be used. These include mucosal delivery, nasal delivery, ocular delivery, transdermal delivery, parenteral controlled release delivery, vaginal delivery, rectal delivery and intrauterine delivery. All of these dosage forms may be manufactured using conven- tional techniques, together with the techniques discussed herein.

There are a number of controlled release drug formulations that are developed pref- erably for oral administration. These include, but are not limited to, osmotic pres- sure-controlled gastrointestinal delivery systems; hydrodynamic pressure-controlled gastrointestinal delivery systems; membrane permeation-controlled gastrointestinal delivery systems, which include microporous membrane permeation-controlled gas- trointestinal delivery devices; gastric fluid-resistant intestine targeted controlled- release gastrointestinal delivery devices; gel diffusion-controlled gastrointestinal delivery systems; and ion-exchange-controlled gastrointestinal delivery systems,

which include cationic and anionic drugs. Additional information regarding controlled release drug delivery systems may be found in Yie W. Chien, Novel Drug Delivery Systems, 1992 (Marcel Dekker, Inc.). some of these formulations will now be dis- cussed in more detail.

Enteric coatings may be applied to tablets to prevent the release of drugs in the stomach either to reduce the risk of unpleasant side effects or to maintain the stabil- ity of the drug which might otherwise be subject to degradation of expose to the gas- tric environment. Most polymers that are used for this purpose are polyacids that function by virtue of the fact that their solubility in aqueous medium is pH- dependent, and they require conditions with a pH higher then normally encountered in the stomach.

Enteric coatings may be used to coat a solid or liquid dosage form of the bioactive species according to the invention. Enteric coatings promote the inventive bioactive species remaining physically incorporated in the dosage form for a specified period when exposed to gastric juice. Yet the enteric coatings are designed to disintegrate in intestinal fluid for ready absorption. Delay of the bioactive species'absorption is dependent on the rate of transfer through the gastrointestinal tract, and so the rate of gastric emptying is an important factor. Some investigators have reported that a multiple-unit type dosage form, such as granules, may be superior to a single-unit type. Therefore, in a preferable embodiment, the bioactive species according to the invention may be contained in an enterically coated multiple-unit dosage form. In a more preferable embodiment, the dosage form of the bioactive species according to the invention is prepared by spray-coating granules of an bioactive species-enteric coating agent solid dispersion on an inert core material. These granules can result in prolonged absorption of the drug with good bioavailability.

Typical enteric coating agents include, but are not limited to, hyd roxypropylmethyl- cellulose phthalate, methacrylic acid-methacrylic acid ester copolymer, polyvinyl acetate-phthalate and cellulose acetate phthalate. Akihiko Hasegawa, Application of solid dispersions of Nifedipine with enteric coating agent to prepare a sustained- release dosage form, Chem. Pharm. Bull. 33: 1615-1619 (1985). Various enteric coating materials may be selected on the basis of testing to achieve an enteric coated dosage form designed ab initio to have a preferable combination of dissolu-

tion time, coating thicknesses and diametral crushing strength. S. C. Porter et al., The Properties of Enteric Tablet Coatings Made From Polyvinyl Acetate-phthalate and Cellulose acetate Phthalate, J. Pharm. Pharmacol. 22: 42p (1970).

On occasion, the performance of an enteric coating may hinge on its permeability.

S. C. Porter et al., The Permeability of Enteric Coatings and the Dissolution Rates of Coated Tablets, J. Pharm. Pharmacol. 34: 5-8 (1981). With such oral drug delivery systems, the drug release process may be initiated by diffusion of aqueous fluids across the enteric coating. Investigations have suggested osmotic driven/rupturing affects as important release mechanisms from enteric coated dosage forms. Roland Bodmeier et al., Mechanical Properties of Dry and Wet Cellulosic and Acrylic Films Prepared from Aqueous Colloidal Polymer Dispersions used in the Coating of Solid Dosage Forms, Pharmaceutical Research, 11: 882-888 (1994).

Another type of useful oral controlled release structure is a solid dispersion. A solid dispersion may be defined as a dispersion of one or more bioactive species in an inert carrier or matrix in the solid state prepared by the melting (fusion), solvent, or melting-solvent method. Akihiko Hasegawa, Super Saturation Mechanism of Drugs from Solid Dispersions with Enteric Coating Agents, Chem. Pharm. Bull. 36: 4941- 4950 (1998). The solid dispersions may be also called solid-state dispersions. The term"coprecipitates"may also be used to refer to those preparations obtained by the solvent methods.

Solid dispersions may be used to improve the solubilities and/or dissolution rates of bioactive species according to the invention that may be poorly water-soluble. See generally Hiroshi Yuasa, et al., Application of the Solid Dispersion Method to the Controlled Release Medicine. Ill. Control of the Release Rate of Slightly Water- Soluble Medicine From Solid Dispersion Granules, Chem. Pharm. Bull. 41 : 397-399 (1993). The solid dispersion method was originally used to enhance the dissolution rate of slightly water-soluble medicines by dispersing the medicines into water- soluble carriers such as polyethylene glycol or polyvinylpyrrolidone, Hiroshi Yuasa, et al., Application of the Solid Dispersion Method to the Controlled Release of Medi- cine. IV. Precise Control of the Release Rate of a Water-Soluble Medicine by Using the Solid Dispersion Method Applying the Difference in the Molecular Weight of a Polymer, Chem. Pharm. Bull. 41: 933-936 (1993).

The selection of the carrier may have an influence on the dissolution characteristics of the dispersed drug because the dissolution rate of a component from a surface may be affected by other components in a multiple component mixture. For exam- ple, a water-soluble carrier may result in a fast release of the drug from the matrix, or a poorly soluble or insoluble carrier may lead to a slower release of the drug from the matrix. The solubility of poorly water soluble bioactive species according to the invention may also be increased owing to some interaction with the carriers.

Examples of carriers useful in solid dispersions according to the invention include, but are not limited to, water-soluble polymers such as polyethylene glycol, polyvi- nylpyrrolidone, or hydroxypropylmethyl-cellulose. Akihiko Hasegawa, Application of Solid Dispersions of Nifedipine with Enteric Coating Agent to Prepare a Sustained- release Dosaae Form, Chem. Pharm. Bull. 33: 1615-1619 (1985).

There are various methods commonly known for preparing solid dispersions. These include, but are not limited to the melting method, the solvent method and the melt- ing-solvent method.

In the melting method, the physical mixture of a drug in a water-soluble carrier is heated directly until it melts. The melted mixture is then cooled and solidified rapidly while rigorously stirred. The final solid mass is crushed, pulverized and sieved. Us- ing this method a super saturation of a solute or drug in a system can often be ob- tained by quenching the melt rapidly from a high temperature. Under such condi- tions, the solute molecule may be arrested in solvent matrix by the instantaneous solidification process. A disadvantage is that many substances, either drugs or car- riers, may decompose or evaporate during the fusion process at high temperatures.

However, this evaporation problem may be avoided if the physical mixture is heated in a sealed container. Melting under a vacuum or blanket of an inert gas such as nitrogen may be employed to prevent oxidation of the drug or carrier.

The solvent method has been used in the preparation of solid solutions or mixed crystals of organic or inorganic bioactive species. Solvent method dispersions may be prepared by dissolving a physical mixture of two solid components in a common solvent, followed by evaporation of the solvent. The main advantage of the solvent

method is that thermal decomposition of drugs or carriers may be prevented be- cause of the low temperature required for the evaporation of organic solvents. How- ever, some disadvantages associated with this method are the higher cost of prepa- ration, the difficulty in completely removing liquid solvent, the possible adverse effect of its supposedly negligible amount of the solvent on the chemical stability of the drug.

Another method of producing solid dispersions is the melting-solvent method. It is possible to prepare solid dispersions by first dissolving a drug in a suitable liquid solvent and then incorporating the solution directly into a melt of polyethylene glycol, obtainable below 70 degrees, without removing the liquid solvent. The selected sol- vent or dissolved adenosine analogs may be selected such that the solution is not miscible with the melt of polyethylene glycol. The polymorphic form of the adenosine analogs may then be precipitated in the melt. Such a unique method possesses the advantages of both the melting and solvent methods. Win Loung Chiou, et al., Pharmaceutical Applications of Solid Dispersion Systems, J. Pharm. Sci. 60: 1281- 1301 (1971).

Another controlled release dosage form is a complex between an ion exchange resin and the bioactive species according to the invention. Ion exchange resin-drug complexes have been used to formulate sustained-release products of acidic and basic drugs. In one preferable embodiment, a polymeric film coating is provided to the ion exchange resin-drug complex particles, making drug release from these par- ticles diffusion controlled. See Y. Raghunathan et al., Sustained-released drug de- livery system) : Coded ion-exchange resin systems for phenylpropanolamine and other drugs, J. Pharm. Sciences 70: 379-384 (1981).

Injectable micro spheres are another controlled release dosage form. Injectable mi- cro spheres may be prepared by non-aqueous phase separation techniques, and spray-drying techniques. Micro spheres may be prepared using polylactic acid or copoly (lactic/glycolic acid). Shigeyuki Takada, Utilization of an Amorphous Form of a Water-Soluble GPllb/Illa Antagonist for Controlled Release From Biodegradable Micro spheres, Pharm. Res. 14: 1146-1150 (1997), and ethyl cellulose, Yoshiyuki Koida, Studies on Dissolution Mechanism of Drugs from Ethyl Cellulose Microcap- sules, Chem. Pharm. Bull. 35: 1538-1545 (1987).

Other controlled release technologies that may be used in the practice of this inven- tion are quite varied. They include SODAS (Spheroidal Oral Drug Absorption Sys- tem), INDAS (Insoluble Drug Absorption System), IPDAS (Intestinal Protective Drug Absorption System), MODAS (Multiporous Oral Drug Absorption System), EFVAS (Effervescent Drug Absorption System), PRODAS (Programmable Oral Drug Ab- sorption System), and DUREDAS (Dual Release Drug Absorption System) available from Elan Pharmaceutical Technologies, Dublin, Ireland. SODAS are multi particu- late dosage forms utilizing controlled release beads. INDAS are a family of drug delivery technologies designed to increase the solubility of poorly soluble drugs.

IPDAS are multi particulate tablet formation utilizing a combination of high density controlled release beads and an immediate release granulate. MODAS are con- trolled release single unit dosage forms. Each tablet consists of an inner core sur- rounded by a semipermeable multiparous membrane that controls the rate of drug release. EFVAS is an effervescent drug absorption system, PRODAS is a family of multi particulate formulations utilizing combinations of immediate release and con- trolled release mini-tablets. DUREDAS is a bilayer tablet formulation providing dual release rates within the one dosage form. Although these dosage forms are known to one of skill, certain of these dosage forms will now be discussed in more detail.

INDAS was developed specifically to improve the solubility and absorption charac- teristics of poorly water soluble drugs. Solubility and, in particular, dissolution within the fluids of the gastrointestinal tract is a key factor in determining the overall oral bioavailability of poorly water soluble drug. By enhancing solubility, one can in- crease the overall bioavailability of a drug with resulting reductions in dosage. IN- DAS takes the form of a high energy matrix tablet. In a preferred embodiment of the invention production involves including adenosine analogs in an amorphous form together with a combination of energy, excipients, and unique processing proce- dures.

Once included in the desirable physical form, the resultant high energy complex may be stabilized by an absorption process that utilizes a novel polymer cross-linked technology to prevent recrystallization. The combination of the change in the physi- cal state of the adenosine analogs according to the invention coupled with the solu- bilizing characteristics of the excipients employed enhances the solubility of the

adenosine analogs according to the invention. The resulting absorbed amorphous drug complex granulate may be formulated with a gel-forming erodable tablet sys- tem to promote substantially smooth and continuous absorption.

IPDAS is a multi-particulate tablet technology that may enhance the gastrointestinal tolerability of potential irritant and ulcerogenic drugs. Intestinal protection is facili- tated by the multi-particulate nature of the IPDAS formulation which promotes dis- persion of an irritant adenosine analog according to the invention throughout the gastrointestinal tract. Controlled release characteristics of the individual beads may avoid high concentration of drug being both released locally and absorbed systemi- cally. The combination of both approaches serves to minimize the potential harm of the adenosine analog according to the invention with resultant benefits to patients.

IPDAS is composed of numerous high density controlled release beads. Each bead may be manufactured by a two step process that involves the initial production of a micromatrix with embedded adenosine analogs according to the invention and the subsequent coating of this micromatrix with polymer solutions that form a rate limit- ing semipermeable membrane in vivo. Once an IPDAS tablet is ingested, it may disintegrate and liberate the beads in the stomach. These beads may subsequently pass into the duodenum and along the gastrointestinal tract, preferably in a con- trolled and gradual manner, independent of the feeding state. Adenosine analog release occurs by diffusion process through the micromatrix and subsequently through the pores in the rate controlling semipermeable membrane. The release rate from the IPDAS tablet may be customized to deliver a drug-specific absorption profile associated with optimized clinical benefit. Should a fast onset of activity be necessary, immediate release granulate may be included in the tablet. The tablet may be broken prior to administration, without substantially compromising drug re- lease, if a reduced dose is required for individual titration.

MODAS is a drug delivery system that may be used to control the absorption of wa- ter soluble adenosine analogs according to the invention. Physically MODAS is a non-disintegrating table formulation that manipulates drug release by a process of rate limiting diffusion by a semipermeable membrane formed in vivo. The diffusion process essentially dictates the rate of presentation of drug to the gastrointestinal fluids, such that the uptake into the body is controlled. Because of the minimal use

of excipients, MODAS can readily accommodate small dosage size forms. Each MODAS tablet begins as a core containing active drug plus excipients. This core is coated with a solution of insoluble polymers and soluble excipients. Once the tablet is ingested, the fluid of the gastrointestinal tract may dissolve the soluble excipients in the outer coating leaving substantially the insoluble polymer. What results is a network of tiny, narrow channels connecting fluid from the gastrointestinal tract to the inner drug core of water soluble drug. This fluid passes through these channels, into the core, dissolving the drug, and the resultant solution of drug may diffuse out in a controlled manner. This may permit both controlled dissolution and absorption.

An advantage of this system is that the drug releasing pores of the tablet are distrib- uted over substantially the entire surface of the tablet. This facilitates uniform drug absorption and reduces aggressive unidirectional drug delivery. MODAS represents a very flexible dosage form in that both the inner core and the outer semipermeable membrane may be altered to suit the individual delivery requirements of a drug. In particular, the addition of excipients to the inner core may help to produce a micro environment within the tablet that facilitates more predictable release and absorption rates. The addition of an immediate release outer coating may allow for develop- ment of combination products.

Additionally, PRODAS may be used to deliver adenosine analogs according to the invention. PRODAS is a multi particulate drug delivery technology based on the pro- duction of controlled release mini tablets in the size range of 1.5 to 4 mm in diame- ter. The PRODAS technology is a hybrid of multi particulate and hydrophilic matrix tablet approaches, and may incorporate, in one dosage form, the benefits of both these drug delivery systems.

In its most basic form, PRODAS involves the direct compression of an immediate release granulate to produce individual mini tablets that contain adenosine analogs according to the invention. These mini tablets are subsequently incorporated into hard gels and capsules that represent the final dosage form. A more beneficial use of this technology is in the production of controlled release formulations. In this case, the incorporation of various polymer combinations within the granulate may delay the release rate of drugs from each of the individual mini tablets. These mini tablets may subsequently be coated with controlled release polymer solutions to provide additional delayed release properties. The additional coating may be necessary in

the case of highly water soluble drugs or drugs that are perhaps gastroirritants where release can be delayed until the formulation reaches more distal regions of the gastrointestinal tract.

Use of"bioactive species"for the preparation of a medicament for the treatment of an individual in need thereof In another embodiment of the present invention, a bioactive species capable of acti- vating a polypeptide toxin and/or capable of initiating de novo synthesis of an acti- vated polypeptide toxin, such as any of the bioactive species described herein, is used for the preparation of a medicament for the treatment of an individual sin need thereof. Preferably, said medicament is for the treatment or prevention of disease by a microbial cell, such as any bacterial disease or bacterial cell mentioned herein.

Said bacterial cell preferably comprises any of the toxins and cognate anti-toxins described herein. The individual treated may be any individual described herein.

Given that toxins described herein are known as being capable of having detrimen- tal effects of other cell types, such as eukaryotic cells, the bioactive species de- scribed herein are also useful for treating any disease caused by unwanted cell growth, such as neoplastic diseases.

Hygienic compositions and methods for reduction or of microbes In another aspect of the present invention, a hygienic composition capable of reduc- ing or eliminating microbes is provided, comprising one or more of the bioactive species disclosed herein. Said hygienic composition may further comprise a hy- gienically-acceptable carrier. By"hygienically-acceptable carrier"is meant any suit- able carrier that does not prevent the composition from having the desired effect of reducing or eliminating microbes. Said hygienic composition may be contacted against a surface in a non-therapeutic method for eliminating or reducing microbial cells. By"surface"is also meant any suitable surface for which reduction or elimina- tion of microbial cells is desirable, for example a wall, floor, toilet basin and so on.

Said surface may in one embodiment be within an environment in which healthcare professionals work, such as a hospital or care home. More preferably, said surface is present on an item of healthcare equipment, such as an item of surgical or medi- cal apparatus, such as a catheter, glove, or medical implant. Said surface may also be found within the home, such as within a kitchen, such as an item of kitchen equipment, particularly surfaces that may be contacted by food.

Method of treating a plant diagnosed with, or at risk of developing, a disease caused by a microbial cell In another aspect of the present invention a method is provided for treating a plant diagnosed with, or at risk of developing, a disease caused by a microbial cell, said microbial cell comprising at least one complex of a polypeptide toxin and an anti- toxin polypeptide and/or at least one polynucleotide encoding a polypeptide toxin and an anti-toxin polypeptide, said method comprising the steps of a) contacting said microbial cell with a bioactive species capable of activating said polypeptide toxin and/or capable of initiating de novo synthesis of activated polypeptide toxin, and/or capable of increasing the total amount of activated polypeptide toxin and b) obtaining in said microbial cell an activated polypeptide toxin in an amount suffi- cient for achieving at least an impaired growth or elimination of said microbial cell in said plant.

Illustrative plant pathogens that may be reduced or eliminated using this method include, but are not restricted to, the group consisting of the genera Agrobacterium, Pseudomonas, Xanthomonas, Erwinia, Ralstonia, and Clavibacter.

Preferred embodiments of the present invention : The following items describe preferred embodiment of the present invention: 1. Method for treating an individual suffering from, or at risk of developing, a dis- ease caused by a microbial cell, comprising at least one complex of a polype- tide toxin and an anti-toxin polypeptide and/or at least one polynucleotide encod- ing a polypeptide toxin and an anti-toxin polypeptide, said method comprising the steps of i) contacting said microbial cell with a bioactive species capable of activating said polypeptide toxin and/or capable of initiating de novo synthesis of acti- vated polypeptide toxin, and/or capable of increasing the total amount of ac- tivated polypeptide toxin and

ii) obtaining in said microbial cell an activated polypeptide toxin in an amount sufficient for achieving at least an impaired growth or elimination of said mi- crobial cell in said individual.

2. Method of item 1 comprising the further step, preferably before step (i), of pro- viding a pharmaceutical composition comprising at least one bioactive species capable of contacting and activating in a microbial cell at least one polypeptide toxin selected from the group of polypeptide toxins consisting of RelE and vari- ants thereof; ParE and variants thereof; VapC and variants thereof, Chp and variants thereof; Hig and variants thereof; Doc and variants thereof; and CcdB and variants thereof, wherein the polypeptide toxin prior to activation optionally forms a complex with an anti-toxin polypeptide capable of reducing or inhibiting the toxic activity of the polypeptide toxin.

3. The method of any of items 1 and 2 wherein the step of contacting the microbial cell with the bioactive species is selected from a) contacting the cell surface of the microbial cell with the bioactive species, and/or b) uptake of the bioactive species in the microbial cell and contacting an in- tracellular component of the microbial cell with the bioactive species.

4. The method of any of items 1 to 3, wherein the step of activation of the at least one polypeptide toxin results from a) de novo synthesis of activated polypeptide toxin, wherein the de novo synthe- sised and activated polypeptide toxin does not form a complex with an anti-toxin polypeptide, and/or b) dissociation of polypeptide toxin and anti-toxin polypeptide present in the same complex, wherein said dissociation results in the release from the complex of polypeptide toxin in an active form, or a form capable of being activated follow- ing dissociation from the anti-toxin polypeptide, and optionally

c) degradation of the anti-toxin 5. Method of any of the items 1-4, wherein said microbial cell comprises a reIBE TA system.

6. Method of item 5, wherein said microbial cell is a gram negative bacteria.

7. Method of item 6, said bacteria is selected from one or more of Brucella melitensis, Brucella suis, Helicobacter pylori, Escherichia coli, Escherichia coli 0157, Shigella flexneri, Coxiella burnetii, Vibrio cholerae, Vibrio parahaemolyti- cus, Vibrio vulnificus, Haemophilus influenzae, Pseudomonas aeruginosa, Pseu- domonas putida KT2440, Pseudomonas syringae, Salmonella typhimurium and Salmonella typhi.

8. Method of item 5, wherein said microbial cell is a gram positive bacteria.

9. Method of item 8, wherein said bacteria is selected from one or more of Myco- bacterium tuberculosis, Enterococcus faecalis, Staphylococcus aureus, Strep- tococcus agalactiae, Streptococcus mutans, Streptococcus pneumonia, or Fu- sobacterium nucleatum 10. Method of any of items 1-4, wherein said microbial cell comprises a vapBC TA system.

11. Method of item 10, wherein said microbial cell is a gram positive bacterium.

12. Method of item 11, wherein said bacterium is selected from Mycobacterium tu- berculosis 13. Method of item 10, wherein said microbial cell is a gram negative bacterium 14. Method of item 13, wherein said bacterium is selected from one or more of Rickettsia conorii, Coxiella burnetii, Haemophilus influenzae, Pseudomonas sy- ringae, Salmonella typhimurium, Salmonella typhi and Leptospira intrerrogans.

15. Method of any of items 1-4, wherein said microbial cell comprises a mazEF TA system.

16. Method of item 15, wherein said microbial cell is a gram positive bacterium.

17. Method of item 16, wherein said microbial cell is selected from one or more of Mycobacterium tuberculosis, Bacillus anthracis, Bacillus cereus, Bacillus halodurans, Clostridium perfringens, Enterococcus faecalis, Listeria monocy- togenes, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus mutans and Streptococcus pneumonia 18. Method of item 15, wherein said microbial cell is a gram negative bacterium.

19. Method of item 18, wherein said microbe is selected from Brucella melitensis, Brucella suis, Rickettsia conorii, Neisseria meningitidis, Escherichia coli, Es- cherichia coli 0157, Shigella flexneri, Vibrio cholerae, Vibrio parahaemolyti- cus, Pseudomonas putida or Leptospira intrerrogans.

20. Method of any of items 1-4, wherein said microbial cell comprises a parDE TA system.

21. Method of item 20, wherein said microbial cell comprises a gram positive bacte- rium.

22. Method of item 21, wherein said microbial cell is selected from Mycobacterium tuberculosis ; Streptococcus agalactiae, or Streptococcus pyogenes.

23. Method of item 20, wherein said microbial cell comprises a gram negative bacte- rium.

24. Method of item 23, wherein said microbial cell is selected from Escherichia coli 0157, Escherichia coli, Coxiella burnetii, Vibrio cholerae, Vibrio parahaemo- lyticus, Vibrio vulnificus, Pseudomonas aeruginosa and Pseudomonas syrin- gae.

25. Method of any of items 1-4, wherein said microbial cell comprises a higBA TA system.

26. Method of item 25, wherein said microbial cell comprises a gram negative bacte- rium.

27. Method of item 26, wherein said microbial cell is selected from Neisseria men- ingitidis, Escherichia coli, Coxiella burnetii, Vibrio cholerae, Haemophilus in- fluenzae, Pseudomonas aeruginosa, Pseudomonas putida KT2440 and Pseu- domonas syringae.

28. Method of any of items 1-4, wherein said microbial cell comprises a phd/doc TA system 29. Method of item 28, wherein said microbial cell comprises a gram positive bacte- rium 30. Method of item 29, wherein said microbial cell is selected from Clostridium tet- ani, Enterococcus faecalis and Streptococcus pneumonia.

31. Method of item 28, wherein said microbial cell comprises a gram negative bacte- rium.

32. Method of item 31, wherein said bacterium is selected from Brucella melitensis, Brucella suis, Neisseria meningitidis, Yersinia pestis, Vibrio cholerae, Pseu- domonas aeruginosa, Salmonella typhimurium and Salmonella typhi.

33. Method of any of items 1-4, wherein said microbial cell comprises a ccdAB TA system 34. Method of item 33, wherein said microbial cell is selected from Escherichia coli or Escherichia coli 0157.

35. Method of any of the previous items, wherein said individual is an animal.

36. Method of any of the previous items, wherein said individual is a vertebrate.

37. Method of any of the previous items, wherein said individual is a mammal.

38. Method of any of the previous items, wherein said individual is a domestic ani- mal.

39. Method of any of the previous items, wherein said individual is a wild animal.

40. Method of any of the previous items, wherein said individual is a human.

41. Method of any of the previous items, wherein said individual is female.

42. Method of any of items 1-40, wherein said individual is male.

43. Method of item 41, wherein said individual is pregnant or lactating.

44. Method of any of the previous items, wherein said individual has undergone en- dotracheal intubation.

45. Method of any of the previous items, wherein said individual has undergone bladder catheterization.

46. Method of any of the previous items, wherein said individual has undergone cen- tral venous catheterization.

47. Method of any of the previous items, wherein said individual has undergone peri- toneal dialysis.

48. Method of any of the previous items, wherein said individual is immunocompro- mised.

49. Method of item 48, wherein said individual has been, is being, or will be treated with an immunosuppressive drug.

50. Method of item 49, wherein said drug comprises one or more steroid 51. Method of item 48, wherein said individual is suffering from a disease not caused by a bacteria.

52. Method of item 51, wherein said individual is suffering one or more of: an auto- immune disease, sarcoidosis, leprosy, cytomegalovirus infections, malaria, a parasitic disease, a fungal disease.

53. Method of item 51 wherein said individual is suffering from a viral infection 54. Method of item 53 wherein said viral infection is caused by one or more of infec- tious bursal disease virus or cytomegalovirus,

55. Method of item 53, wherein said individual has HIV or AIDS.

56. Method of item 48 wherein said individual has one or more of: trauma, burns, a wound or a surgical wound.

57. Method of any of items 1-56, wherein said individual is a neonate 58. Method of any of items 1-56, wherein said individual is an infant 59. Method of any of items 1-56, wherein said individual is 3-6 years old 60. Method of any of items 1-56, wherein said individual is 6-10 years old 61. Method of any of items 1-56, wherein said individual is 10-20 years old 62. Method of any of items 1-56, wherein said individual is 20-30 years old 63. Method of any of items 1-56, wherein said individual is 40-50 years old 64. Method of any of items 1-56, wherein said individual is 50-60 years old 65. Method of any of items 1-56, wherein said individual is 60-70 years old 66. Method of any of items 1-56, wherein said individual is 70-80 years old 67. Method of any of items 1-56, wherein said individual is 70-130 years old 68. Method of any of items 1-4, wherein said disease is selected from : an abscess, acrodermatitis chronica atrophicans (ACA), actinomycosis, acute bacterial Prostatitis, anthrax (Black Bane or malignant pustule or Wool sorter's disease or Tanner's disease), Australian tick typhus (Australian Spotted Fever or Queen- sland Tick Typhus), Bang's disease (Brucellosis), bartonellosis (Verruga peru- ana or carrion's disease or Oroya fever),"Black death" (plague), bacillary an- giomatosis, bacterial vaginosis, Bejel (endemic syphilis), blennorrhea of the newborn, blepharitis, a boil, botulism, Boutonneuse fever (fievre boutonneuse or tick typhus), Brazilian purpuric fever, Brill-Zinsser disease (recrudescent typhus), bronchitis, Brucellosis, Bullous impetigo, Buruli ulcers (Mycoburuli ulcers), cam- pylobacteriosis, chromobacteriosis, cryptosporidiosis, carate (Mal del pinto or Pinta), carditis, carbuncle, cat scratch fever (cat scratch disease), chancroid, chlamydia, cholera, clap, conjunctivitis (pink eye), cystitis or pyelonephritis, da- cryocytitis, diphtheria-Corynebacterium diphtheriae (G+ rod: non-sporulating : non-filamentous), disseminated Intravascular Coagulation, donovanosis (granu- loma inguinale), Durand-Nicholas-Favre disease (lymphogranuloma venereum (LGV) ), ehrlichiosis, epidemic typhus, endemic Relapsing fever, endocarditis, endophthalmitis, enteric infections, epidemic relapsing fever, epiglottitis, ery- sipeloid (erysipelothricosis), erysipelis, erythema chronicum migrans, erythema marginatum, erythema multiforme, erythema nodosum, erythema nodosum lep- rosum, erythrasma, Fitz-Hugh-Curtis syndrome (perihepatitis), Flinders Island

Spotted Fever, frambesia (yaws), furunculosis (boil-furuncle), folliculitis, gas gangrene, glanders, granuloma inguinale (donovanosis), hamburger disease (hemolytic uremic syndrome), Hansen's disease (leprosy), hard chancre (syphi- lis), Haverhill fever (rat bite fever), Helicobacterosis (duodenal ulcers), hidrade- nitis, human monocytic ehrlichiosis, human granulocytic ehrlichiosis, impetigo, inclusion conjunctivitis (swimming pool conjunctivitis or pannus), infantile diar- rhea, Israeli spotted fever, Legionnaire's pneumonia, leprosy (Hansen's dis- ease), leptospirosis, listerosis, lockjaw (tetanus), Ludwig's angina, Lyme dis- ease, Lymphogranuloma venereum (LGV), Malta fever (Brucellosis), Mediteran- nean spotted fever, melioidosis (Whitmore's disease), meningitis (spotted fever), Montezuma's Revenge (traveler's diarrhea), Multiple Organ Dysfunction Syn- drome or MODS, murine typhus, myositis, myocarditis, necrotizing fasciitis, no- cardiosis (nocardia), nongonococcal urethritis, North Asian tick typhus- Rickettsia sibirica (G-intracellular ; tick-borne), nosocomial infections, opthalmia neonatorium, Oriental Spotted Fever, otitis media, otitis externa, osteomyelitis, parrot fever (Ornithosis or Psittacosis), PCP pneumonia, Peliosis hepatica, pel- vic Inflammatory Disease (PID), pertussis (whooping cough), pigbel, Pinta, pitted keratolysis, plague, pneumonia, pontiac fever, postanginal septicemia (Le- mierre's Syndrome), prostatitis, pseudomembranous colitis, puerperal fever, pylephlebitis, pyelonephritis, Q fever, Quinsy-Peritonsillar abscess, rat bite fe- ver, Reiter Syndrome, relapsing fever, rheumatic fever, rhinoscleroma (Kleb- siella rhinoscleromatis), rickettsialpox, Rocky Mountain spotted fever, salmonel- losis, scarlet fever (scarlatina), scalded skin syndrome, scrub typhus, Sennetsu fever (ehrlichiosis), sepsis or septic shock, septic arthritis, shigellosis, shipping fever, Siberian tick typhus, sinusitis, sporadic typhus, staphylococcal enterotoxin poisoning, Stie-Hordeola, Strep. Throat, stomach ulcers, stomach cancer, Sys- temic Inflammatory Response Syndrome or SIRS, Tabes dorsalis (tertiary syphilis), Tuberculosis (TB), tooth decay, Toxic Shock Syndrome (TSS), trench fever (5-day fever), trench mouth (Vincent's disease), Trachoma, Trichomycosis axillaris, tularemia (rabbit fever or deer fly fever), typhoid fever, typhus fever, urethritis, ulcus molle (soft chancre or chancroid), undulant fever, urethritis, bac- terial vaginosis, vaginitis, Waterhouse-Friderichsen syndrome, Weil's diseases, Whipple's disease, yaws, yersinosis-Yersinia enterocolitica 69. Method of any of items 1-4, wherein said disease is stomach cancer.

70. Method of any of items 1-4, wherein said disease is a sexually transmitted disease.

71. Method of item 70 wherein said disease is bacterial vaginosis.

72. Method of item 70 wherein said microbial cell is selected from Bacteroides spp, Gardnerella vaginalis or Mobiluncus spp.

73. Method of item 70 wherein said disease is a Chlamydial infection or Lymphogranuloma venereum.

74. Method of item 73 wherein said microbial cell is Chlamydia trachomatis.

75. Method of item 70 wherein said disease is an enteric infection.

76. Method of item 260 wherein said microbial cell is selected from Campylobacter fetus, Shigella sp. , Escherichia coli, Salmonella sp.

77. Method of item 70 wherein said disease is a Group B streptococcal infections 78. Method of item 77 wherein said microbial cell is Streptococcus agalactiae 79. Method of item 70 wherein said disease is Granuloma inguinale (donovanosis) 80. Method of item 79 wherein said microbial cell is Calymmatobacterium granulomatis 81. Method of item 70 wherein said disease is NGU or Nongonococcal urethritis 82. Method of item 81 wherein said microbial cell is selected from Chlamydia trachomatis, and Gardnerella vaginalis.

83. Method of item 70 wherein said disease is Pelvic Inflammatory Disease (PID) 84. Method of item 83 wherein said microbial cell is selected from N. gonorrhoeae, Chlamydia trachomatis, Anaerobic bacteria, Facultative Gram negative rods, Actinomyces israelii 85. Method of item 70 wherein said disease is syphilis 86. Method of item 85 wherein said microbial cell is Treponema pallidum 87. Method of any of items 1-4, wherein said disease is transmitted via consumption of unpasteurised dairy products 88. Method of item 87 wherein said disease is selected from Campylobacteriosis, Salmonellosis, Hemolytic Uremic Syndrome, Yersiniosis, Listeriosis, Tuberculosis, Brucellosis, Cryptosporidiosis, Staphylococcal enterotoxin poisoning or Q fever.

89. Method of any of items 1-4, wherein said disease is an eye disease

90. Method of item 89 wherein said eye disease is selected from pink eye (conjunctivitis), trachoma and Opthalmia neonatorium.

91. Method of item 90 wherein said microbial cell is selected from Haemophilus aegyptius, Chlamydia trachomatis or Neisseria gonorrhoeae 92. Method of any of items 1-4, wherein said disease is a skin disease 93. Method of item 92 wherein said disease is selected from Impetigo, Folliculitis, boils, Scalded Skin Syndrome, Erysipelas, leprosy, Lyme disease, syphilis, chancroid, Rocky Mountain Spotted Fever 94. Method of item 93 wherein said microbial cell is selected from Staphylococcus aureus, Streptococcus pyogenes, Borrelia burgdorferi, Treponema pallidum, Rickettsia rickettsii, Bacteroides spp, Gardnerella vaginalis, and Mobiluncus spp.

95. Method of any of items 1-4 wherein said disease is a disease of the gastrointestinal tract.

96. Method of item 95 wherein said microbial cell is selected from Staphylococcus aureus, Bacillus cereus, Clostridium perfringens, Clostridium botulinum, E. coli (EPEC), E. coli (ETEC), E. coli (EAggEC or enteroadherent EC), Vibrio cholerae 01, Vibrio cholerae non-01, Enteropathogenic (EPEC) E. coli, Clostridium difficile, Vibrio parahemolyticus, Bacillus anthracis, E. coli (EIEC), E. coli (EHEC), Salmonella spp, Salmonella typhimurium, Salmonella typhi, Shigella dysenteriae type 1, Shigella sonnei/flexneri, Yersinia enterocolitica, Shigella sp. , Enteroinvasive E. coli (EIEC), Enterohemorrhagic E. coli (EHEC), Yersinia sp., Francisella tularensis, Helicobacter pylori, Staphylococcus aureus, Yersinia pseudotuberculosis, Listeria monocytogenes, Vibrio parahaemolyticus, Vibrio sp. , Vibrio vulnificus, Clostridium perfringens, Bacillus cereus, Aeromonas hydrophila, Plesiomonas shigelloides, Streptococcus sp., enterovirulent Escherichia coli group (EEC Group), Escherichia coli-enterotoxigenic (ETEC), Escherichia coli 0157 : H7 enterohemorrhagic (EHEC) and Clostridium difficile 97. Method of any of items 95-96, wherein said disease of the gastrointestinal tract is inflammatory Gastroenteritis.

98. Method of item 97 wherein said microbial cell is selected from one or more of Vibrio cholerae, Vibrio cholerae 01, Vibrio cholerae non-01, Enterotoxigenic (ETEC) E. coli, Enteropathogenic (EPEC) E. coli, Enteroaggregative (EAggEC) E. coli, Clostridium difficile, Vibrio parahemolyticus, Bacillus anthracis, E. coli (EIEC), E. coli (EHEC), Salmonella spp, Salmonella typhimurium, Salmonella

typhi, Shigella dysenteriae type 1, Shigella sonnei/flexneri, and Yersinia enterocolitica.

99. Method of any of items 95-96, wherein said disease of the gastrointestinal tract is invasive Gastroenteritis.

100. Method of item 99 wherein said microbial cell is selected from one or more of Shigella sp. , Salmonella sp. , Enteroinvasive E. coli (EIEC), Enterohem- orrhagic E. coli (EHEC), Vibrio vulnificus, Yersinia sp., Francisella tularensis or Helicobacter pylori.

101. Method of any of items 1-4, wherein said disease is pneumonia.

102. Method of item 101 wherein said microbial cell is selected from one or more of Acinetobacter sp. , Actinomyces sp., Bacillus anthracis, Bacteroides melaninogenicus, Bordetella pertussis, Burkholderia pseudomallei, Burkholderia mallei, Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Coxiella burnetii (Q-fever), Escherichia coli, Francisella tularensis, Fusobacte- rium sp., Hemophilus influenzae, Klebsiella pneumoniae, Legionella pneumo- phila, Moraxella catarrhalis, Mycobacterium tuberculosis, Mycobacterium sp., Neisseria meningitidis, Nocardia sp. , Porphyromonas sp., Prevotella sp. , Pro- teus sp. , Pseudomonas aeruginosa, Serratia sp. , Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus, agalactiae, Staphylococcus aureus, Peptostreptococcus sp. , and Yersinia pestis.

103. Method of any of items 1-4, wherein said disease is transmitted via an arthropod, such as an insect, for example one or more of a tick, a mite, an insect larva, a louse, a flea, a fly or a gnat.

104. Method of item 103, wherein said disease is selected from Scrub Typhus (Tsutsugamushi disease), Rickettsial pox, Tularemia, Rocky Mountain Spotted Fever, Endemic Relapsing Fever, Sennetsu fever, erlichiosis, Epidemic typhus, Trench fever, bacillary angiomatosis, bacillary peliosis, Louse-borne relapsing fever or epidemic relapsing fever, Plague, Murine typhus, Tularemia, Bartonellosis, Oroya fever, Carrion's disease, Tick-borne Relapsing Fever, Tularemia and Cat Scratch Fever 105. Method of any of items 1-4, wherein said disease is transmitted via an airborne mode of transmission.

106. Method of item 105, wherein said disease is selected from diphtheria, pneumonia, tuberculosis, Legionnaire's disease, a skin diseases, impetigo, cellulitis, a systemic bacterial disease, rheumatic fever or menigitis.

107. Method of any of items 1-4, wherein said disease is transmitted via direct contact of the bacterium with the individual, such as by the bacterium contacting one or more of the skin, mucous membrane or underlying tissues.

108. Method of items 107, wherein said disease is selected from anthrax, cat-scratch fever, gas gangrene, leprosy, peptic ulcers, staphylococcal infections, syphilis, tetanus, staphylococcal diseases or gonorrhea 109. Method of any of items 1-4, wherein said disease is transmitted via ingestion of food and/or water.

110. Method of item 109, wherein said disease is selected from Campylobactergastroenteritis, salmonellosis, shigellosis, listeriosis, traveler's diarrhea, typhoid fever, botulism, cholera, staphylococcal food poisoning, Campylobacteriosis, Hemolytic Uremic Syndrome, Yersiniosis, Listeriosis, Tuberculosis, Brucellosis, Cryptosporidiosis, Staphylococcal enterotoxin poisoning or Q fever.

111. Method of any of items 1-4 wherein said disease is a disease of the respiratory tract.

112. Method of item 111, wherein said disease is selected from strep throat, acute tuberculosis, chronic tuberculosis and pneumonia.

113. Method of any of items 1-4, wherein said disease is a nosocomial infection.

114. Method of item 113, wherein said nosocomial infection is a urinary tract infection.

115. Method of item 113 wherein said nosocomial infection is a surgical site infection.

116. Method of item 113 wherein said nosocomial infection is pneumonia 117. Method of item 113 wherein said nosocomial infection is a systemic infection.

118. Method of any of items 1-4, wherein said microbial cell is an opportunistic bacterial pathogen.

119. Method of item 118, wherein said opportunistic bacterial pathogen is selected from Staphylococcus aureus, E. coli, Stenotrophomonas (Xanthomonas) maltophilia, Salmonella sp. , Rhodococcus equi. Shigella flexneri, Pseudomonas aeruginosa, Listonella anguillarum, Burkholderia cepacia or Mycobacterium, Nocardia asteroides, Nocardia brasiliensis, and Nocardia otitidiscaviarum.

120. Method of any of items 1-4, wherein said disease is a dental disease.

121. Method of item 120, wherein said dental disease is selected from tooth decay and/or periodontal disease 122. Method of any of the previous items, wherein said microbial cell is re- sistant to one or more antibiotics.

123. Method of item 122 wherein said microbial cell is selected from Staphylococcus sp. , MRSA (methicillin-resistant staph aureus) Campylobacter sp, Listeria monocytogenes, Pneumococcus sp., Haemophilus influenzae, Bacil- lus subtilis, Streptococcus pneumoniae, Mycobacterium tuberculosis, Salmo- nella sp. , E. coli, Enterococcus sp., Klebsiella pneumoniae, Pseudomonas aeruginosa, Klebsiella oxytoca, Morganella morganii, Enterobacter agglomer- ans, Enterococcus faecalis, Enterococcus faeium and Staphylococcus epider- midis 124. Method of any of the previous items, wherein said bioactive species is administered to said individual in an amount from 0.1 mg-150 mg.

125. Method of any of the previous items, wherein said contacting is per- formed 1-4 times daily.

126. Method of any of the previous items, wherein said contacting is per- formed 2-3 times daily.

127. Method of any of the previous items, whereby said method is used in combination with another medical treatment.

128. Method of item 127, whereby said medical treatment is an organ transplant.

129. Method of item 127, whereby said medical treatment is chemotherapy.

130. Method of item 127, whereby said medical treatment is radiotherapy.

131. Method of item 127, whereby said medical treatment is a cancer treatment.

132. Method of item 127, whereby said medical treatment is a cystic fibro- sis treatment.

133. Method of item 127, whereby said medical treatment causes or con- tributes to immunodeficiency of said individual.

134. Method of item 127, whereby said medical treatment is used to treat AIDS or HIV.

135. Method of item 127, whereby said medical treatment is an anti- microbial treatment.

136. Method of item 135, wherein said treatment comprises administration of at least one anti-microbial compound, such as any of the following : - one or more cell wall synthesis inhibitor, such as a beta-lactam - penicillin - a cephalosporin - Vancomycin - protein synthesis inhibitor, such as an Aminoglycoside (streptomycin), a Tet- racycline, a Macrolide (erythromycin), an Oxazolidinone - one or more nucleic acid metabolism inhibitor - a Sulfonamide - Trimethoprim - a Rifamycin one or more DNA gyrase inhibitor, such as a Quinolone, a derivative of Qui- nolone, a fluorinated derivative of Quinolone or a Novobiocin.

137. Method of any of items 1-136, wherein said polypeptide toxin is from the RelE toxin family.

138. Method of item 137, wherein said polypeptide toxin comprises a se- quence selected from SEQ ID NO : 2,4, 6,8, 10, 12, 14, and 16.

139. Method of item 137, wherein said polypeptide toxin comprises a se- quence that is substantially identical to SEQ ID NO : 2,4, 6,8, 10,12, 14, and 16.

140. Method of item 137, wherein said polypeptide toxin comprises a se- quence with at least 80 % sequence identity to one or more of SEQ ID NO : 2,4, 6,8, 10,12, 14, and 16.

141. Method of item 137, wherein said polypeptide toxin comprises a se- quence with at least 85 % sequence identity to one or more of SEQ ID NO : 2,4, 6,8, 10,12, 14, and 16.

142. Method of item 137, wherein said polypeptide toxin comprises a se- quence with at least 90 % sequence identity to one or more of SEQ ID NO : 2,4, 6,8, 10,12, 14, and 16.

143. Method of item 137, wherein said polypeptide toxin comprises a se- quence with at least 95 % sequence identity to one or more of SEQ ID NO : 2,4, 6,8, 10,12, 14, and 16.

144. Method of item 137, wherein said polypeptide toxin comprises a se- quence with at least 99 % sequence identity to one or more of SEQ ID NO : 2,4, 6,8, 10, 12,14, and 16.

145. Method of item 137, wherein said polypeptide toxin comprises a sequence, characterised in that said sequence produces an E value of 10-4 or less when compared to one or more of SEQ ID N0 : 2,4, 6,8, 10,12, 14, and 16 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

146. Method of item 137, wherein said polypeptide toxin comprises a sequence, characterised in that said sequence produces an E value of 10-5 or less when compared to one or more of SEQ ID N0 : 2,4, 6,8, 10,12, 14, and 16 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

147. Method of item 137, wherein said polypeptide toxin comprises a sequence, characterised in that said sequence produces an E value of 10-1° or less when compared to one or more of SEQ ID N0 : 2,4, 6,8, 10,12, 14, and 16 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

148. Method of item 137 and/or 147, wherein said polypeptide toxin com- prises a sequence selected from SEQ ID N0 : 17-97 149. Method of any of items 1-136, wherein said polypeptide toxin is from the VapC toxin family.

150. Method of item 149, wherein said polypeptide toxin comprises a se- quence selected from SEQ ID N0 : 99,101, 103 and 105 151. Method of item 149 wherein said polypeptide toxin comprises a se- quence that is substantially identical to SEQ ID N0 : 99,101, 103 and 105.

152. Method of item 149, wherein said polypeptide toxin comprises a se- quence with at least 80 % sequence identity to one or more of SEQ ID NO : 99, 101,103 and 105.

153. Method of item 149, wherein said polypeptide toxin comprises a se- quence with at least 85 % sequence identity to one or more of SEQ ID N0 : 99, 101,103 and 105.

154. Method of item 149, wherein said polypeptide toxin comprises a se- quence with at least 90 % sequence identity to one or more of SEQ ID N0 : 99, 101,103 and 105.

155. Method of item 149, wherein said polypeptide toxin comprises a se- quence with at least 95 % sequence identity to one or more of SEQ ID N0 : 99, 101,103 and 105.

156. Method of item 149, wherein said polypeptide toxin comprises a se- quence with at least 99 % sequence identity to one or more of SEQ ID NO : 99, 101,103 and 105.

157. Method of item 149, wherein said polypeptide toxin comprises a sequence, characterised in that said sequence produces an E value of 10-5 or less when compared to one or more of SEQ ID N0 : 99,101, 103 and 105 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

158. Method of item 149, wherein said polypeptide toxin comprises a sequence, characterised in that said sequence produces an E value of 10-4 or less when compared to one or more of SEQ ID NO : 99,101, 103 and 105 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

159. Method of item 149, wherein said polypeptide toxin comprises a sequence, characterised in that said sequence produces an E value of 1 0-l) or less when compared to one or more of SEQ ID N0 : 99,101, 103 and 105 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

160. Method of item 149 and/or 159 wherein said polypeptide toxin com- prises a sequence selected from SEQ ID N0 : 106-154 161. Method of any of items 1-136, wherein said polypeptide toxin is from the MazF toxin family.

162. Method of item 161, wherein said polypeptide toxin comprises a se- quence selected from SEQ ID N0 : 155 and 160.

163. Method of item 161, wherein said polypeptide toxin comprises a se- quence that is substantially identical to SEQ I D NO : 155 and 160.

164. Method of item 161, wherein said polypeptide toxin comprises a se- quence with at least 80 % sequence identity to one or more of SEQ I D NO : 155 and 160.

165. Method of item 161, wherein said polypeptide toxin comprises a se- quence with at least 85 % sequence identity to one or more of SEQ ID N0 : 155 and 160.

166. Method of item 161, wherein said polypeptide toxin comprises a se- quence with at least 90 % sequence identity to one or more of SEQ ID N0 : 155 and 160.

167. Method of item 161, wherein said polypeptide toxin comprises a se- quence with at least 95 % sequence identity to one or more of SEQ ID NO : 155 and 160.

168. Method of item 161, wherein said polypeptide toxin comprises a se- quence with at least 99 % sequence identity to one or more of SEQ ID NO : 155 and 160.

169. Method of item 161, wherein said polypeptide toxin comprises a sequence, characterised in that said sequence produces an E value of 10-4 or less when compared to one or more of SEQ ID NO : 155 and 160 using the BLAST algo- rithm version (2.04) set to the default parameters defined herein.

170. Method of item 161, wherein said polypeptide toxin comprises a sequence, characterised in that said sequence produces an E value of 10-5 or less when compared to one or more of SEQ ID NO : 155 and 160 using the BLAST algo- rithm version (2.04) set to the default parameters defined herein.

171. Method of item 161, wherein said polypeptide toxin comprises a sequence, characterised in that said sequence produces an E value of 10-1° or less when compared to one or more of SEQ ID NO : 155 and 160 using the BLAST algo- rithm version (2.04) set to the default parameters defined herein.

172. Method of item 161 and/or 171, wherein said polypeptide toxin com- prises a sequence selected from SEQ ID NO : 161-205.

173. Method of any of items 1-136, wherein said polypeptide toxin is from the ParE toxin family.

174. Method of item 173, wherein said polypeptide toxin comprises se- quence with SEQ ID NO : 207 175. Method of item 173, wherein said polypeptide toxin comprises a se- quence that is substantially identical to SEQ ID NO : 207.

176. Method of item 173, wherein said polypeptide toxin comprises a se- quence with at least 80 % sequence identity to SEQ ID NO : 207.

177. Method of item 173, wherein said polypeptide toxin comprises a se- quence with at least 85 % sequence identity to SEQ ID NO: 207.

178. Method of item 173, wherein said polypeptide toxin comprises a se- quence with at least 90 % sequence identity to SEQ ID NO: 207.

179. Method of item 173, wherein said polypeptide toxin comprises a se- quence with at least 95 % sequence identity to SEQ ID NO: 207.

180. Method of item 173, wherein said polypeptide toxin comprises a se- quence with at least 99 % sequence identity to SEQ ID NO: 207.

181. Method of item 173, wherein said polypeptide toxin comprises a sequence, characterised in that said sequence produces an E value of 104 or less when compared to SEQ ID NO: 207 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

182. Method of item 173, wherein said polypeptide toxin comprises a sequence, characterised in that said sequence produces an E value of 10-5 or less when compared to SEQ ID NO: 207 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

183. Method of item 173, wherein said polypeptide toxin comprises a sequence, characterised in that said sequence produces an E value of 10-1° or less when compared to SEQ ID NO: 207 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

184. Method of item 173 and/or 183 wherein said polypeptide toxin com- prises a sequence selected from SEQ ID N0 : 208-219.

185. Method of any of items 1-136 wherein said polypeptide toxin is from the HigB toxin family.

186. Method of item 185, wherein said polypeptide toxin comprises a se- quence with SEQ ID NO: 221.

187. Method of item 185, wherein said polypeptide toxin comprises a se- quence that is substantially identical to SEQ ID NO: 221.

188. Method of item 185, wherein said polypeptide toxin comprises a se- quence with at least 80 % sequence identity to one or more of SEQ ID NO: 221.

189. Method of item 185, wherein said polypeptide toxin comprises a se- quence with at least 85 % sequence identity to one or more of SEQ ID NO: 221.

190. Method of item 185, wherein said polypeptide toxin comprises a se- quence with at least 90 % sequence identity to one or more of SEQ ID NO: 221.

191. Method of item 185, wherein said polypeptide toxin comprises a se- quence with at least 95 % sequence identity to one or more of SEQ ID NO: 221.

192. Method of item 185, wherein said polypeptide toxin comprises a se- quence with at least 99 % sequence identity to one or more of SEQ ID NO : 221.

193. Method of item 185, wherein said polypeptide toxin comprises a sequence, characterised in that said sequence produces an E value of 10-4 or less when compared to one or more of SEQ ID NO: 221 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

194. Method of item 185, wherein said polypeptide toxin comprises a sequence, characterised in that said sequence produces an E value of 10-5 or less when compared to one or more of SEQ ID NO: 221 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

195. Method of item 185, wherein said polypeptide toxin comprises a sequence, characterised in that said sequence produces an E value of 10-'° or less when compared to one or more of SEQ ID NO: 221 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

196. Method of item 185 or 195 wherein said polypeptide toxin comprises a sequence selected from SEQ ID N0 : 222-240.

197. Method of any of items 1-136, wherein said polypeptide toxin is from the Doc toxin family.

198. Method of item 197, wherein said polypeptide toxin comprises a se- quence selected from SEQ ID NO: 242 199. Method of item 197, wherein said polypeptide toxin comprises a se- quence that is substantially identical to SEQ ID NO: 242.

200. Method of item 197, wherein said polypeptide toxin comprises a se- quence with at least 80 % sequence identity to one or more of SEQ ID NO: 242.

201. Method of item 197, wherein said polypeptide toxin comprises a se- quence with at least 85 % sequence identity to one or more of SEQ ID NO: 242.

202. Method of item 197, wherein said polypeptide toxin comprises a se- quence with at least 90 % sequence identity to one or more of SEQ ID NO: 242.

203. Method of item 197, wherein said polypeptide toxin comprises a se- quence with at least 95 % sequence identity to one or more of SEQ ID NO: 242.

204. Method of item 197, wherein said polypeptide toxin comprises a se- quence with at least 99 % sequence identity to one or more of SEQ ID NO: 242.

205. Method of item 197, wherein said polypeptide toxin comprises a se- quence, characterised in that said sequence produces an E value of 10-4 or less when compared to one or more of SEQ ID NO: 242 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

206. Method of item 197, wherein said polypeptide toxin comprises a sequence, characterised in that said sequence produces an E value of 10-5 or less when compared to one or more of SEQ ID NO: 242 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

207. Method of item 197, wherein said polypeptide toxin comprises a sequence, characterised in that said sequence produces an E value of 10-1° or less when compared to one or more of SEQ ID NO: 242 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

208. Method of item 197 and/or 207 wherein said polypeptide toxin com- prises a sequence selected from SEQ ID N0 : 243-257.

209. Method of any of items 1-136, wherein said polypeptide toxin is from the CcdB toxin family.

210. Method of item 209, wherein said polypeptide toxin comprises a se- quence selected from SEQ ID NO: 259.

211. Method of item 209, wherein said polypeptide toxin comprises a se- quence that is substantially identical to SEQ ID NO: 259.

212. Method of item 209, wherein said polypeptide toxin comprises a se- quence with at least 80 % sequence identity to one or more of SEQ ID NO: 259.

213. Method of item 209, wherein said polypeptide toxin comprises a se- quence with at least 85 % sequence identity to one or more of SEQ ID NO: 259.

214. Method of item 209, wherein said polypeptide toxin comprises a se- quence with at least 90 % sequence identity to one or more of SEQ ID NO: 259.

215. Method of item 209, wherein said polypeptide toxin comprises a se- quence with at least 95 % sequence identity to one or more of SEQ ID NO: 259.

216. Method of item 209, wherein said polypeptide toxin comprises a se- quence with at least 99 % sequence identity to one or more of SEQ ID NO: 259.

217. Method of item 209, wherein said polypeptide toxin comprises a sequence, characterised in that said sequence produces an E value of 10-4 or less when compared to one or more of SEQ ID NO: 259 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

218. Method of item 209, wherein said polypeptide toxin comprises a sequence, characterised in that said sequence produces an E value of 10-5 or less when compared to one or more of SEQ ID NO: 259 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

219. Method of item 209, wherein said polypeptide toxin comprises a sequence, characterised in that said sequence produces an E value of 10-1° or less when compared to one or more of SEQ ID NO: 259 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

220. Method of item 209-219, wherein said polypeptide toxin comprises a se- quence selected from SEQ ID N0 : 260-263.

221. Method of any of items 1-136, wherein said polypeptide antitoxin is from the RelB family.

222. Method of item 221 wherein said polypeptide antitoxin comprises a sequence selected from SEQ ID NO : 1,3, 5,7, 9,11, 13 and 15.

223. Method of item 221, wherein said polypeptide antitoxin comprises a sequence that is substantially identical to one or more of SEQ ID NO : 1,3, 5,7, 9, 11, 13 and 15 224. Method of item 221, wherein said polypeptide antitoxin comprises a sequence with at least 80 % sequence identity to one or more of SEQ ID : 1,3, 5,7, 9,11, 13 and 15 225. Method of item 221, wherein said polypeptide antitoxin comprises a sequence with at least 85 % sequence identity to one or more of SEQ ID NO : 1,3, 5,7, 9,11, 13 and 15.

226. Method of item 221, wherein said polypeptide antitoxin comprises a sequence with at least 90 % sequence identity to one or more of SEQ ID NO : 1,3, 5,7, 9,11, 13 and 15.

227. Method of item 221, wherein said polypeptide antitoxin comprises a sequence with at least 95 % sequence identity to one or more of SEQ ID NO : 1,3, 5,7, 9,11, 13 and 15.

228. Method of item 221, wherein said polypeptide antitoxin comprises a sequence with at least 99 % sequence identity to one or more of SEQ ID NO : 1,3, 5,7, 9,11, 13 and 15.

229. Method of item 221, wherein said polypeptide antitoxin comprises a sequence, characterised in that said sequence produces an E value of 104 or less when compared to one or more of SEQ ID NO : 1,3, 5,7, 9,11, 13 and 15, us- ing the BLAST algorithm version (2.04) set to the default parameters defined herein.

230. Method of item 221, wherein said polypeptide antitoxin comprises a sequence, characterised in that said sequence produces an E value of 10-5 or less when compared to one or more of SEQ ID NO : 1,3, 5,7, 9,11, 13 and 15 us- ing the BLAST algorithm version (2.04) set to the default parameters defined herein.

231. Method of item 221 and/or 230, wherein said polypeptide antitoxin comprises a sequence, characterised in that said sequence produces an E value of 10-1° or less when compared to one or more of SEQ ID NO : 1,3, 5,7, 9,11, 13 and 15 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

232. Method of any of items 1-136 wherein said polypeptide antitoxin is from the VapB family 233. Method of item 232, wherein said polypeptide antitoxin comprises a sequence selected from SEQ ID NO : 98,100, 102 and 104.

234. Method of item 232, wherein said polypeptide antitoxin comprises a sequence that is substantially identical to one or more of SEQ ID NO : 98,100, 102 and 104.

235. Method of item 232, wherein said polypeptide antitoxin comprises a sequence with at least 80 % sequence identity to one or more of SEQ ID : 98, 100,102 and 104.

236. Method of item 232, wherein said polypeptide antitoxin comprises a sequence with at least 85 % sequence identity to one or more of SEQ ID NO : 98,100, 102 and 104.

237. Method of item 232, wherein said polypeptide antitoxin comprises a sequence with at least 90 % sequence identity to one or more of SEQ ID NO : 98,100, 102 and 104.

238. Method of item 232, wherein said polypeptide antitoxin comprises a sequence with at least 95 % sequence identity to one or more of SEQ ID NO : 98,100, 102 and 104.

239. Method of item 232, wherein said polypeptide antitoxin comprises a sequence with at least 99 % sequence identity to one or more of SEQ ID NO : 98,100, 102 and 104.

240. Method of item 232, wherein said polypeptide antitoxin comprises a sequence, characterised in that said sequence produces an E value of 104 or less when compared to one or more of SEQ ID NO : 98,100, 102 and 104, using the BLAST algorithm version (2.04) set to the default parameters defined herein.

241. Method of item 232, wherein said polypeptide antitoxin comprises a se- quence, characterised in that said sequence produces an E value of 10-5 or less when compared to one or more of SEQ ID NO : 98,100, 102 and 104 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

242. Method of item 232 and/or 241, wherein said polypeptide antitoxin comprises a sequence, characterised in that said sequence produces an E value of 10-1° or less when compared to one or more of SEQ ID NO : 98,100, 102 and 104 using the BLAST algorithm version (2.04) set to the default parameters de- fined herein.

243. Method of any of items 1-136, wherein said polypeptide antitoxin is from the MazE family.

244. Method of item 243, wherein said polypeptide antitoxin comprises a sequence selected from SEQ ID NO: 156,157, 158 and 159.

245. Method of item 243, wherein said polypeptide antitoxin comprises a sequence that is substantially identical to one or more of SEQ ID NO: 156,157, 158 and 159.

246. Method of item 243, wherein said polypeptide antitoxin comprises a sequence with at least 80 % sequence identity to one or more of SEQ ID : 156, 157,158 and 159.

247. Method of item 243, wherein said polypeptide antitoxin comprises a sequence with at least 85 % sequence identity to one or more of SEQ ID NO: 156,157, 158 and 159.

248. Method of item 243, wherein said polypeptide antitoxin comprises a sequence with at least 90 % sequence identity to one or more of SEQ ID NO: 156,157, 158 and 159.

249. Method of item 243, wherein said polypeptide antitoxin comprises a sequence with at least 95 % sequence identity to one or more of SEQ ID NO: 156,157, 158 and 159.

250. Method of item 243, wherein said polypeptide antitoxin comprises a sequence with at least 99 % sequence identity to one or more of SEQ ID NO: 156,157, 158 and 159.

251. Method of item 243, wherein said polypeptide antitoxin comprises a sequence, characterised in that said sequence produces an E value of 104 or less when compared to one or more of SEQ ID NO: 156,157, 158 and 159, us- ing the BLAST algorithm version (2.04) set to the default parameters defined herein.

252. Method of item 243, wherein said polypeptide antitoxin comprises a se- quence, characterised in that said sequence produces an E value of 10-5 or less when compared to one or more of SEQ ID NO: 156,157, 158 and 159 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

253. Method of item 243 and/or 252, wherein said polypeptide antitoxin comprises a sequence, characterised in that said sequence produces an E value of 10-1° or less when compared to one or more of SEQ ID NO: 156,157, 158

and 159 and 104 using the BLAST algorithm version (2.04) set to the default pa- rameters defined herein.

254. Method of any items 1-136 wherein said polypeptide antitoxin is from the ParD family 255. Method of item 254, wherein said polypeptide antitoxin comprises a sequence with SEQ ID NO : 206.

256. Method of item 254, wherein said polypeptide antitoxin comprises a sequence that is substantially identical to SEQ ID NO : 206.

257. Method of item 254, wherein said polypeptide antitoxin comprises a sequence with at least 80 % sequence identity to SEQ ID : 206.

258. Method of item 254, wherein said polypeptide antitoxin comprises a sequence with at least 85 % sequence identity to SEQ ID NO: 206.

259. Method of item 254, wherein said polypeptide antitoxin comprises a sequence with at least 90 % sequence identity to SEQ ID NO: 206 260. Method of item 254, wherein said polypeptide antitoxin comprises a sequence with at least 95 % sequence identity to one or more of SEQ ID NO: 206.

261. Method of item 254, wherein said polypeptide antitoxin comprises a sequence with at least 99 % sequence identity to SEQ ID NO: 206.

262. Method of item 254, wherein said polypeptide antitoxin comprises a sequence, characterised in that said sequence produces an E value of 104 or less when compared to SEQ ID NO : 206, using the BLAST algorithm version (2.04) set to the default parameters defined herein.

263. Method of item 254, wherein said polypeptide antitoxin comprises a sequence, characterised in that said sequence produces an E value of 10-5 or less when compared to one or more of SEQ ID NO : 206 using the BLAST algo- rithm version (2.04) set to the default parameters defined herein.

264. Method of item 254 and/or 263, wherein said polypeptide antitoxin comprises a sequence, characterised in that said sequence produces an E value of 10-1° or less when compared to SEQ ID NO: 206, using the BLAST algorithm version (2.04) set to the default parameters defined herein.

265. Method of any of items 1-136, wherein said polypeptide antitoxin is from the HigA family 266. Method of item 265 wherein said polypeptide antitoxin comprises a sequence with SEQ ID NO : 220.

267. Method of item 265, wherein said polypeptide antitoxin comprises a sequence that is substantially identical to SEQ ID NO: 220.

268. Method of item 265, wherein said polypeptide antitoxin comprises a sequence with at least 80 % sequence identity to SEQ ID : 220.

269. Method of item 265, wherein said polypeptide antitoxin comprises a sequence with at least 85 % sequence identity to SEQ ID NO: 220.

270. Method of item 265, wherein said polypeptide antitoxin comprises a sequence with at least 90 % sequence identity to SEQ ID NO: 220 271. Method of item 265, wherein said polypeptide antitoxin comprises a sequence with at least 95 % sequence identity to SEQ ID NO: 220.

272. Method of item 265, wherein said polypeptide antitoxin comprises a sequence with at least 99 % sequence identity to SEQ ID NO: 220.

273. Method of item 265, wherein said polypeptide antitoxin comprises a sequence, characterised in that said sequence produces an E value of 104 or less when compared to SEQ ID NO: 220, using the BLAST algorithm version (2.04) set to the default parameters defined herein.

274. Method of item 265, wherein said polypeptide antitoxin comprises a se- quence, characterised in that said sequence produces an E value of 10-5 or less when compared to one or more of SEQ ID NO: 220 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

275. Method of item 265 and/or 274, wherein said polypeptide antitoxin comprises a sequence, characterised in that said sequence produces an E value of 10-1° or less when compared to SEQ ID NO: 220, using the BLAST algorithm version (2.04) set to the default parameters defined herein.

276. Method of any of items 1-136, wherein said polypeptide antitoxin is from the Phd family.

277. Method of item 276, wherein said polypeptide antitoxin comprises a sequence selected from SEQ ID NO: 241.

278. Method of item 276, wherein said polypeptide antitoxin comprises a sequence that is substantially identical to SEQ ID NO: 241.

279. Method of item 276, wherein said polypeptide antitoxin comprises a sequence with at least 80 % sequence identity to SEQ ID : 241.

280. Method of item 276, wherein said polypeptide antitoxin comprises a sequence with at least 85 % sequence identity to SEQ ID NO: 241.

281. Method of item 276, wherein said polypeptide antitoxin comprises a sequence with at least 90 % sequence identity to SEQ ID NO : 241 282. Method of item 276, wherein said polypeptide antitoxin comprises a sequence with at least 95 % sequence identity to SEQ ID NO: 241.

283. Method of item 276, wherein said polypeptide antitoxin comprises a sequence with at least 99 % sequence identity to SEQ ID NO : 241.

284. Method of item 276, wherein said polypeptide antitoxin comprises a sequence, characterised in that said sequence produces an E value of 104 or less when compared to SEQ ID NO : 241, using the BLAST algorithm version (2.04) set to the default parameters defined herein.

285. Method of item 276, wherein said polypeptide antitoxin comprises a sequence, characterised in that said sequence produces an E value of 10-5 or less when compared to one or more of SEQ ID NO : 241 using the BLAST algo- rithm version (2.04) set to the default parameters defined herein.

286. Method of item 276 and/or 285, wherein said polypeptide antitoxin comprises a sequence, characterised in that said sequence produces an E value of 10-1° or less when compared to SEQ ID NO : 241, using the BLAST algorithm version (2.04) set to the default parameters defined herein.

287. Method of any of items 1-136, wherein said polypeptide antitoxin is from the CcdA family 288. Method of item 287, wherein said polypeptide antitoxin comprises a sequence selected from SEQ ID NO : 258.

289. Method of item 287, wherein said polypeptide comprises a sequence that is substantially identical to SEQ ID NO : 258.

290. Method of item 287, wherein said polypeptide antitoxin comprises a sequence with at least 80 % sequence identity to SEQ ID : 258.

291. Method of item 287, wherein said polypeptide antitoxin comprises a sequence with at least 85 % sequence identity to SEQ ID NO: 258.

292. Method of item 287, wherein said polypeptide antitoxin comprises a sequence with at least 90 % sequence identity to SEQ ID NO : 258.

293. Method of item 287, wherein said polypeptide antitoxin comprises a sequence with at least 95 % sequence identity to one or more of SEQ ID NO : 258.

294. Method of item 287, wherein said polypeptide antitoxin comprises a sequence with at least 99 % sequence identity to SEQ ID NO : 258.

295. Method of item 287, wherein said polypeptide antitoxin comprises a sequence, characterised in that said sequence produces an E value of 104 or less when compared to SEQ ID NO: 258, using the BLAST algorithm version (2.04) set to the default parameters defined herein.

296. Method of item 287, wherein said polypeptide antitoxin comprises a se- quence, characterised in that said sequence produces an E value of 10-5 or less when compared to one or more of SEQ ID NO: 258, using the BLAST algorithm version (2.04) set to the default parameters defined herein.

297. Method of item 287 and/or 296, wherein said polypeptide antitoxin comprises a sequence, characterised in that said sequence produces an E value of 10-1° or less when compared to SEQ ID NO: 258, using the BLAST algorithm version (2.04) set to the default parameters defined herein.

298. Method of any of items 1-136, wherein said anti-toxin polypeptide is the cognate anti-toxin to any of the toxin polypeptides described in items 137- 220.

299. Method of any of items 1-136, wherein said polynucleotide encoding a polypeptide toxin encodes a polypeptide toxin described in any of items 137- 220.

300. Method of item 299, wherein said polynucleotide encoding a polype- tide antitoxin encodes a polypeptide antitoxin described in any of items 221-297.

301. Method for the evaluation of the ability of a compound to interfere with a bacterial toxin-antitoxin complex, comprising: a) providing a compound to be evaluated for the ability to interfere with a bacterial toxin-antitoxin complex, and b) providing a first polypeptide comprising a bacterial toxin or a fragment thereof capable of binding an antitoxin, and c) providing a second polypeptide comprising said antitoxin or a fragment thereof capable of binding said toxin, and d) incubating said compound, said first polypeptide and said second polypeptide under conditions allowing binding of said first polypeptide to said second poly- peptide, and e) detecting a signal from said incubation mixture indicative of the degree of bind- ing of said first polypeptide to said second polypeptide, and

evaluating whether or not the presence of said compound has affected the bind- ing of said first polypeptide to said second polypeptide by comparison of the signal detected in step e), with a reference value indicative of the binding of said first polypeptide to said second polypeptide in the absence of said compound.

302. Method of item 301, wherein step f) is done by comparison with a par- allel control experiment, wherein said first polypeptide and said second polype- tide are incubated under conditions allowing binding of said first polypeptide to said second polypeptide, in the absence of said compound.

303. Method of item 301 or 302, wherein said toxin is selected from the tox- ins described in items 137-297.

304. Method of any of items 301-303, wherein said anti-toxin is selected from the antitoxins described in items 221-297.

305. Method of any of items 301-304, wherein said method is a biochemical method.

306. Method of item 305, wherein said biochemical method is performed using purified toxin and/or purified antitoxin.

307. Method of any of items 301-306, wherein one of said polypeptides is immobilised.

308. Method of any of items 301-307, wherein one of said polypeptides is fused to an enzymatic or fluorescent reporter.

309. Method of any of items 301-308, wherein said method is an in vivo method.

310. Method of item 309, wherein said method is cell-based.

311. Method of item 310, wherein said cell is recombinant.

312. Method of any of items 310-311, wherein said method is a bacterial two-hybrid method.

313. Method of any of items 301-312, wherein said signal is generated by a level of enzymatic activity.

314. Method of any of items 301-313 wherein said signal is generated by a level of fluorescence.

315. Method of any of items 301-314 with the further step of repeating said method at least once, with a different bacterial toxin-antitoxin complex.

316. Method of item 315 wherein said different toxin is selected from the toxins described in items 137-220.

317. Method of item 315 and/or item 316, wherein said different antitoxin is selected from the antitoxins described in items 221-297.

318. Bioactive species capable of activating a bacterial polypeptide toxin and/or capable of initiating de novo synthesis of an activated bacterial polypep- tide toxin, said species comprising one or more of the following groups: a- peptides, (3-peptides, y-peptides, co-peptides, mono-, di-and tri-substituted a- peptides, (3-peptides, y-peptides, (D-peptides, peptides wherein the amino acid residues are in the L-form or in the D-form, vinylogous polypeptides, glycopoly- peptides, polyamides, vinylogous sulfonamide peptides, polysulfonamides, con- jugated peptides comprising e. g. prosthetic groups; polyesters, polysaccharides, polycarbamates, polycarbonates, polyureas, polypeptidylphosphonates, polyure- thanes, azatides, oligo N-substituted glycines, polyethers, ethoxyformacetal oli- gomers, poly-thioethers, polyethylene glycols (PEG), polyethylenes, polydisul- fides, polyarylene sulfides, polynucleotides, PNAs, LNAs, morpholinos, oligo pyr- rolinones, polyoximes, polyimines, polyethyleneimines, polyimides, polyacetals, polyacetates, polystyrenes, polyvinyl, lipids, phospholipids, glycolipids, polycyclic compounds comprising e. g. aliphatic or aromatic cycles, including polyhetero- cyclic compounds; proteoglycans, and polysiloxanes, 319. Bioactive species of capable of activating a bacterial polypeptide toxin and/or capable of initiating de novo synthesis of an activated bacterial polype- tide toxin, wherein said bioactive species comprises a scaffold structure, said scaffold structure comprising a plurality of covalently linked functional entities se- lected from one or more of the following groups: a-peptides, p-peptides, y- peptides, co-peptides, mono-, di-and tri-substituted a-peptides, p-peptides, y- peptides, co-peptides, peptides wherein the amino acid residues are in the L-form or in the D-form, vinylogous polypeptides, glycopoly-peptides, polyamides, viny- logous sulfonamide peptides, polysulfonamides, conjugated peptides comprising e. g. prosthetic groups, polyesters, polysaccharides, polycarbamates, polycar- bonates, polyureas, polypeptidylphosphonates, polyurethanes, azatides, oligo N- substituted glycines, polyethers, ethoxyformacetal oligomers, poly-thioethers, polyethylene glycols (PEG), polyethylenes, polydisulfides, polyarylene sulfides, polynucleotides, PNAs, LNAs, morpholinos, oligo pyrrolinones, polyoximes, poly- imines, polyethyleneimines, polyimides, polyacetals, polyacetates, polystyrenes, polyvinyl, lipids, phospholipids, glycolipids, polycyclic compounds comprising

e. g. aliphatic or aromatic cycles, including polyheterocyclic compounds, pro- teoglycans, and polysiloxanes.

320. Bioactive species according to item 319, wherein the plurality of func- tional entities is from 2 to 200, for example from 2 to 100, such as from 2 to 80, for example from 2 to 60, such as from 2 to 40, for example from 2 to 30, such as from 2 to 20, for example from 2 to 15, such as from 2 to 10, such as from 2 to 8, for example from 2 to 6, such as from 2 to 4, for example 2, such as from 3 to 100, for example from 3 to 80, such as from 3 to 60, such as from 3 to 40, for example from 3 to 30, such as from 3 to 20, such as from 3 to 15, for example from 3 to 15, such as from 3 to 10, such as from 3 to 8, for example from 3 to 6, such as from 3 to 4, for example 3, such as from 4 to 100, for example from 4 to 80, such as from 4 to 60, such as from 4 to 40, for example from 4 to 30, such as from 4 to 20, such as from 4 to 15, for example from 4 to 10, such as from 4 to 8, such as from 4 to 6, for example 4, for example from 5 to 100, such as from 5 to 80, for example from 5 to 60, such as from 5 to 40, for example from 5 to 30, such as from 5 to 20, for example from 5 to 15, such as from 5 to 10, such as from 5 to 8, for example from 5 to 6, for example 5, such as from 6 to 100, for example from 6 to 80, such as from 6 to 60, such as from 6 to 40, for example from 6 to 30, such as from 6 to 20, such as from 6 to 15, for example from 6 to 10, such as from 6 to 8, such as 6, for example from 7 to 100, such as from 7 to 80, for example from 7 to 60, such as from 7 to 40, for example from 7 to 30, such as from 7 to 20, for example from 7 to 15, such as from 7 to 10, such as from 7 to 8, for example 7, for example from 8 to 100, such as from 8 to 80, for example from 8 to 60, such as from 8 to 40, for example from 8 to 30, such as from 8 to 20, for example from 8 to 15, such as from 8 to 10, such as 8, for ex- ample 9, for example from 10 to 100, such as from 10 to 80, for example from 10 to 60, such as from 10 to 40, for example from 10 to 30, such as from 10 to 20, for example from 10 to 15, such as from 10 to 12, such as 10, for example from 12 to 100, such as from 12 to 80, for example from 12 to 60, such as from 12 to 40, for example from 12 to 30, such as from 12 to 20, for example from 12 to 15, such as from 14 to 100, such as from 14 to 80, for example from 14 to 60, such as from 14 to 40, for example from 14 to 30, such as from 14 to 20, for example from 14 to 16, such as from 16 to 100, such as from 16 to 80, for example from 16 to 60, such as from 16 to 40, for example from 16 to 30, such as from 16 to 20, such as from 18 to 100, such as from 18 to 80, for example from 18 to 60,

such as from 18 to 40, for example from 18 to 30, such as from 18 to 20, for ex- ample from 20 to 100, such as from 20 to 80, for example from 20 to 60, such as from 20 to 40, for example from 20 to 30, such as from 20 to 25, for example from 22 to 100, such as from 22 to 80, for example from 22 to 60, such as from 22 to 40, for example from 22 to 30, such as from 22 to 25, for example from 25 to 100, such as from 25 to 80, for example from 25 to 60, such as from 25 to 40, for example from 25 to 30, such as from 30 to 100, for example from 30 to 80, such as from 30 to 60, for example from 30 to 40, such as from 30 to 35, for ex- ample from 35 to 100, such as from 35 to 80, for example from 35 to 60, such as from 35 to 40, for example from 40 to 100, such as from 40 to 80, for example from 40 to 60, such as from 40 to 50, for example from 40 to 45, such as from 45 to 100, for example from 45 to 80, such as from 45 to 60, for example from 45 to 50, such as from 50 to 100, for example from 50 to 80, such as from 50 to 60, for example from 50 to 55, such as from 60 to 100, for example from 60 to 80, such as from 60 to 70, for example from 70 to 100, such as from 70 to 90, for example from 70 to 80, such as from 80 to 100, for example from 80 to 90, such as from 90 to 100.

321. Bioactive species of any of items 318-320, wherein said bioactive species is a"small molecule".

322. Bioactive species of items 318-321, comprising functional entities linked by one or more type of chemical bond, selected from peptide bonds, sul- fonamide bonds, ester bonds, saccharide bonds, carbamate bonds, carbonate bonds, urea bonds, phosphonate bonds, urethane bonds, azatide bonds, pep- toid bonds, ether bonds, ethoxy bonds, thioether bonds, single carbon bonds, double carbon bonds, triple carbon bonds, disulfide bonds, sulfide bonds, phos- phodiester bonds, oxime bonds, imine bonds and imide bonds.

323. Bioactive species according to any of items 318-322, wherein said bioactive species comprises a backbone structure comprising or essentially con- sisting of one or more molecular group (s) selected from-NHN (R) CO- ;- NHB (R) CO- ;-NHC (RR') CO- ;-NHC (=CHR) CO- ;-NHC6 H4 CO- ;-NHCH2 CHRCO- ;-NHCHRCH2 CO- ;-COCH2- ;-COS- ;-CONR- ;-COO- ;-CSNH- ;- CH2 NH- ;-CH2CH2- ;-CH2 S- ;-CH2 SO- ;-CH2SO2- ;-CH (CH3) S- ;-CH=CH- ;- NHCO- ;-NHCONH- ;-CONHO- ;-C (=CH2) CH2-;-PO2-NH-;-PO2-CH2-;-PO2- CH2N+-;-SO2NH--; and lactams.

324. Bioactive species according to any of items 318-323, wherein said bioactive species is defined by one or more of the following structural limits : <BR> <BR> <BR> <BR> 3 # HDO # 5 and/or<BR> <BR> <BR> <BR> <BR> <BR> 2sHACs9and/or<BR> <BR> <BR> <BR> <BR> <BR> 2sRTBs8and/or 1 : 5 RNG : 5 4 and/or - 0. 4 s log P # 5.6 and/or 40 sMR s130 325. Bioactive species of item 324 wherein said bioactive species is defined by 2 of said structural limits.

326. Bioactive species of item 324, wherein said bioactive species is de- fined by 3 of said structural limits.

327. Bioactive species of item 324, wherein said bioactive species is de- fined by 4 of said structural limits.

328. Bioactive species of item 324, wherein said bioactive species is de- fined by 5 of said structural limits.

329. Bioactive species of item 324, wherein said bioactive species is de- fined by 6 of said structural limits.

330. Bioactive species of any of items 324-329, wherein said bioactive spe- cies is further defined within the limits 0 : 5 HDO < 2 331. Bioactive species of any of items 324-330, wherein said bioactive spe- cies is further defined within the limits 2 S log P # 3.

332. Bioactive species of any of items 324-331, wherein said bioactive spe- cies is either lipophilic and/or encapsulated in a lipophilic carrier.

333. Bioactive species of any of items 324-332, wherein said bioactive spe- cies is identifiable using the methods of any of items 301-317.

334. Hygienic composition capable of reducing or eliminating microbial cells, comprising one or more of the bioactive species of items 318-333.

335. Hygienic composition of item 334, further comprising a hygienically- acceptable carrier.

336. Non-therapeutic method for eliminating or reducing microbial cells, comprising contacting a surface with the hygienic composition of items 334 or 335.

337. Method of item 336, wherein said surface is on an item of hospital equipment.

338. Method of treating a plant diagnosed with, or at risk of developing, a disease caused by a microbial cell, said microbial cell comprising at least one complex of a polypeptide toxin and an anti-toxin polypeptide and/or at least one polynucleotide encoding a polypeptide toxin and an anti-toxin polypeptide, said method comprising the steps of a) contacting said microbial cell with a bioactive species capable of activating said polypeptide toxin and/or capable of initiating de novo synthesis of activated polypeptide toxin, and/or capable of increasing the total amount of activated polypeptide toxin and b) obtaining in said microbial cell an activated polypeptide toxin in an amount suffi- cient for achieving at least an impaired growth or elimination of said microbial cell in said plant.

339. Method of item 338, wherein said bioactive species is selected from the bioactive species of items 318-333.

340. A pharmaceutical formulation comprising a bioactive species of any of items 318-333, or a pharmaceutically acceptable salt thereof, together with a pharmaceutical acceptable carrier or diluent therefor.

341. The pharmaceutical formulation of item 340 comprising more than one bioactive species of any of items 318-333, or a phamaceutically acceptable salt thereof.

342. The pharmaceutical formulation of any of items 340-341, formulated for parenteral administration.

343. The pharmaceutical formulation of any of items 340-341, formulated for oral administration 344. The pharmaceutical formulation of any of items 340-341, formulated for topical administration.

345. The pharmaceutical formulation of any of items 340-341, formulated for parenteral administration.

346. The pharmaceutical formulation of any of items 340-341, formulated for transdermal administration.

347. The pharmaceutical formulation of any of items 340-341, formulated as a suppository.

348. The pharmaceutical formulation of any of items 340-341, formulated for nasal administration.

349. The pharmaceutical formulation of any of items 340-341, formulated for aerosol administration.

350. Use of a bioactive species described in any of items 318-333, capable of activating a polypeptide toxin of a bacterial toxin; antitoxin complex and/or ca- pable of initiating de novo synthesis of an activated polypeptide toxin and/or ca- pable of increasing the amount of activated polypeptide toxin; for the manufacture of a medicament for the treatment of an individual in need thereof.

351. Use of item 350, wherein said medicament is for the treatment or pre- vention of disease in said individual caused by a bacterium harbouring one or more toxin: anti-toxin complexes.

352. Use of any of items 350-351, wherein said disease is selected from the list of diseases in item 68.

353. Use of any of items 350-352, wherein said microbial cell is selected from the microbial cells described in any of items 5-34.

354. Use of any of items 350-353, wherein said toxin and/or antitoxin is selected from the toxins and antitoxins described in items 137-298.

355. Use of any of items 350-354, wherein said individual is selected from any of the individuals described in items 35-67.

Description of Figures Figure 1: Schematic representation of fluorescence polarization measurements.

When a small fluorescent molecule is excited with polarized light, the dipole will tumble randomly in solution, and when emission is measured through a second po- larizing filter, parallel and perpendicular to the excitation plane of polarization, equal intensities will be observed and result in a low polarization value. When the fluores- cent molecule binds to a macromolecule, the molecule rotates slowly, orients in the plane of polarization, and yields higher intensity when the polarizes are parallel than perpendicular, resulting in a high polarization value (Methods 22,61-70 (2000)).

Figure 2: In vivo testing and screening for compounds that disrupt the interaction between a toxin (denoted X) and antitoxin (denoted Y). Any compound identified

that leads to a disruption of the TA interaction is thus expected to lead to a repres- sion of ß-galactosidase synthesis, provided that it can enter the cell and contain in vivo activity. It may be necessary to use a harmless version of the toxin for these studies to avoid killing of the cells. Such toxin derivatives are already available.

(Karimova et al., (1998) PNAS 95: 5752-6. ) Figure 3: (A) Schematic drawing that explains the titration induction principle, (B) optical density and (C) colony forming units pr ml (cfu/ml) after production of RelE6CS mutant protein in wild-type and drelBE E. coli cells. Cells of MG1655/pKP3103 (pBAD: : relE6CS) and MG1655dre/BE/pKP3103 were grown in M9 minimal medium supplemented with 50-, ug/ml chloramphenicol, amino acids in defined amounts and 0,5% glycerol. The relE6CS gene encodes a RelE protein that has its C-terminal six aa substituted with TVTVTV. This mutant RelE protein does not inhibit translation in vitro (Pedersen et al., 2002). At time zero, transcription of the relE6CS gene was induced by addition of 0.2% arabinose. At the time-points indicated, appropriate dilutions of the cultures were plated on LA-plates containing 50 Rg/ml chloramphenicol and 0.2% arabinose.

Figure 4: Peptide Scanning Arrays used to identify linear sequences of antitoxin that interact with partner toxins. Nitrocellulose membranes spotted with peptides derived from RelB (A) and MazE (B) and probed with either RelE-GST (A) or MazF-GST (B). The peptides were designed so that there was a shift of 2 aa between two con- secutive peptides. 50 Rg of GST-RelE (A) or GST-MazF (B) was incubated with the membranes ON at 4°C. To visualize the binding of the GST fusions, the membranes were incubated with mouse anti-GST antibody in addition to HRP-conjugated goat anti-mouse antibody the following day.

Examples Example 1 : Cell killing by activation of endogenous RelE of E coli RelB neutralizes RelE by direct protein-protein interaction. Therefore, in E. coli wild-type cells that contain native ReIBE complexes, ectopic overproduction of non- toxic variants of RelE that still can bind RelB should titrate endogenous RelB away from the active wild-type RelE and confer cell killing. To test this, we used a non-

toxic mutant variant of RelE that has its 6 C-terminal codons substituted to TVTVTV (called RelE6CS) (Pedersen et al., 2002). The RelE6CS variant does not inhibit translation in vitro and this explains its lack of cell killing activity in vivo. As a first attempt to activate endogenous RelE, we used the titration-principle as illustrated in Figure 3A.

Plasmid pKP3103 (Figure 3A) carries the relE6CS gene downstream of the pBAD promoter and therefore produces RelE6CS upon addition of arabinose (0.2%) to the growth medium. Cells of MG1655/pKP3103 and MG1655dre/BE/pKP3103 were grown in M9 minimal medium supplemented with amino acids in defined amounts and 0. 5% glycerol. At an optical density of approximately 0.2 (OD450), 0.2% arabi- nose was added to induce transcription of the relE6CS gene. Figure 3B shows that the optical density of MG1655dre/BE/pKP3103 continued to increase after addition of arabinose. In contrast, the growth of MG1655/pKP3103 rapidly ceased. Simulta- neously, cells of MG1655/pKP3103 were plated on LA-plates containing 50 gg/ml chloramphenicol and 0.2% arabinose at different time-points before and after addi- tion of arabinose. The number of colony forming units continued to increase in MG1655Jre/BE/pKP3103 after addition of arabinose (Figure 3C). In contrast, the viability of MG1655dre/BE/pKP3103 was severely reduced after addition of arabi- nose (Figure 3C). The first sample was plated on LA-plates without arabinose. Thus, production of RelE6CS resulted in inhibition of cell growth and in a reduction of the number of viable cells only if the plasmid-carrying strain encoded a chromosomal copy of the relBE locus. This result shows that endogenous RelE can be activated from outside the cell and kill and/or inhibit the growth of the cells.

Example 2: Identification of linear sequences in RelB and MazE that interact with the toxin partner.

RelB antitoxin forms a tight complex with RelE and MazE antitoxin forms a tight complex with MazF. We used peptide arrays to identify linear stretches of amino acids in the antitoxins RelB and MazE that interact with the cognate toxins. We used two peptide"scanning"arrays that consisted of peptides of 15 aa in length and cor- responded from aa 1-15,3-17 etc. to 65-79 (ReIB) or to 68-82 (MazE). The array peptides were covalently bound to a whatman 50 cellulose support by their C- termini.

For detection of toxin interaction we used fusions between toxins-RelE and MazF to GST. The peptide array membranes were probed with GST-RelE or GST-MazF fu- sion proteins. From biochemical experiments we knew that the fusion proteins were biologically active and bind their cognate antitoxins avidly. To visualize the binding of the GST fusion proteins, the membranes were incubated with mouse anti-GST antibody in addition to HRP-conjugated goat anti-mouse antibody.

We identified two series of ReIB-derived peptides that were recognized by RelE- GST. The first series corresponded to the N-terminal part of RelB and consisted of the two peptides ReIB7-21 and ReIB9_23. This region covers the aa sequence RID- DELKARSYAALEKM. The underlined sequence represents the aa which are pre- sent in both peptides. The second series consisted of the peptide RelB3953 and cov- ers the sequence ADNERLPFKQTLLSD.

We identified three series of MazE-derived peptides that were recognized by MazF- GST (Fig. 4B). The strongest interaction was to the series of peptides MazE45-59, MazE53-67-MazE59-73 and MazE6377 covering EPVRKEPVFTLAELVNDITPENL- HENIDWGEPK of MazE. The underlined sequence is present in more than one of the MazE peptides that is recognized by GST-MazF. The aa sequence in bold rep- resent the peptide MazE55-69. This peptide is recognized very strongly by GST-MazF.

These results are in very good agreement with the known structure of the MazEF complex (Kamada et al. 2003). The peptides that bound MazF all contain aa that interact with MazF in the crystals. The strongest interaction between MazE and MazF involves a region called"site 2"of MazE which consists of aa 54-67. With the exception of 1 aa all 14"site 2"aa were included in peptide MazE5569 which was the peptide that was recognized the most strongly by GST-MazF. The GST-MazF fusion did not bind RelB derived peptides and GST-RelE derived peptides did not bind to the MazE peptides (control reactions). These result show that small linear peptides derived from antitoxins can bind in vitro to their cognate toxins with a high specificity.

Such small peptides demonstrate that peptidomimetics can be used as lead com- pounds that break toxin-antitoxin activity and thereby activate the toxins.

Example 3: Examples of in vitro methods for the evaluation of the abilitv of a com- pound to interfere with a bacterial toxin-antitoxin complex, as disclosed herein (a) Release of toxin from solid phase immobilized antitoxin.

The antitoxin is purified and immobilized to a solid support (e. g. microtiter well).

There are numerous companies specializing in wells for protein immobilization (e. g.

Corning Inc.) from whom standard protocols are available. The corresponding toxin is fused to an enzyme with an easily detectable activity, exemplified by alkaline phosphatase. The fusion protein is tested for biological activity in vivo before purifi- cation. Interaction between antitoxin and tagged toxin proteins can now be estab- lished in microtiter wells and these form the basis for screening of combinatorial chemical libraries that are commercially available (Chemical Diversity Inc. and oth- ers). Any low molecular compound that disrupts the interaction between the TA pair will lead to release of the toxin fused to alkaline phosphatase. The amount of re- leased toxin can be assayed with great sensitivity by transferring the supernatant to a clean microtiter well and performing an alkaline phosphatase assay. For maximal sensitivity phosphate substrates yielding fluorescent products (eg. Fluorescein di- phosphate-FDP, Molecular Probes Inc.) should be used. Upon action of alkaline phosphatase FDP is hydrolyzed to fluorescein that fluoresces with a maximum of 518 nm upon excitation with a maximum of 494 nm which makes this substrate suit- able for detection in standard ELISA readers.

All screening procedures described here are readily automatized using robotics and plate readers currently available.

(b) Disruption of TA interaction in solution The antitoxin is purified as above. The corresponding toxin is purified and flores- cently labeled by standard procedures). Toxin and antitoxin are mixed in microtiter wells and fluorescence polarization determined in a FP plate reader. Combinatorial chemical libraries can be screened for their ability in splitting the toxin antitoxin in- teraction because active substances will give rise to a lower polarization value (see Fig. 1). The principle behind fluorescence polarization is that when a fluorescent molecule is excited with plane polarized light, light is emitted in the same polarized plane, provided that the molecule remains stationary throughout the excited state (which has a duration of 4 nanoseconds for fluorescein). If the molecule rotates and tumbles out of this plane during the excited state, light is emitted in a different plane from the excitation light. If vertically polarized light is exciting the fluorophore, the

intensity of the emitted light can be monitored in vertical and horizontal planes (de- gree of movement of emission intensity from vertical to horizontal plane is related to the mobility of the fluorescently labeled molecule). If a molecule is very large, little movement occurs during excitation and the emitted light remains highly polarized. If a molecule is small, rotation and tumbling is faster and the emitted light is depolar- ized relative to the excitation plane. This procedure has the advantage that it is per- formed in solution in a single microtiter plate, i. e. no transfer between plates are necessary. Furthermore it allows real time detection of TA disruption (kinetics) and it is insensitive to variations in concentrations. The method is very sensitive.

Example 4: Examples of in vivo methods for the evaluation of the ability of a com- pound to interfere with a bacterial toxin-antitoxin complex as disclosed herein (a) Bacterial two hybrid system used as an indicator for TA interaction.

Toxin antitoxin interaction in vivo can be monitored using the bacterial two hybrid system developed by Karimova and coworkers (Proc Natl Acad Sci U S A 95,5752, 1999). The basis of this system is the activation certain genes in E. coli, for exam- ple lacZ, by the CAP protein in complex with cAMP. If the Cya protein of Bordetella pertussis is split into two domains (T18 and T25), cAMP is no longer formed and gene activation by CAP no longer takes place (Fig. 2). However, if proteins that normally interacts (toxin and antitoxin) are fused to T18 and T25, respectively, these will be brought into close proximity of each other and functional CAP will be formed.

Thus, interaction between the toxin and antitoxin will lead to derepression of the lac promoter, and an increase in beta-galactosidase activity that can be easily moni- tored.

(b) TA interaction in vivo monitored by BRET (bioluminescence resonance energy transfer) A given antitoxin is genetically fused to a bioluminescent Renilla luciferase. In the presence of substrate, coelenterazine, it will emit light with an emission optimum of 480 nm. This is close to the excitation maximum for the YFP protein to which the toxin will be fused. Interaction of the toxin and antitoxin brings luciferase and the YFP proteins into close proximity such that resonance energy transfer takes place (Xu Y, Piston DW, Johnson CH. A bioluminescence resonance energy transfer (BRET) system: application to interacting circadian clock proteins. Proc Natl Acad Sci U S A 96,151, 1996). Thus, in presence of a substrate for luciferase we are ex-

pected to observe YFP fluorescence due to strong TA interaction. BRET has previ- ously been used to demonstrate interaction between a number of proteins (ref).

Any compound identified in la or lb that lead to a disruption of TA interaction is thus expected to lead to to reduced resonance energy transfer and reduced YFP flores- cence, provided that it can enter the cell and contain in vivo activity. It may be nec- essary to use a harmless version of the toxin for these studies to avoid killing of the cells.

Example 5: Example of bioinformatics search of genome databases to indentifv toxin-antitoxin pairs Definition of"Gi"amino acid (protein) and DNA sequence identifier: "GI"identifiers are numbers assigned by NCBI to all sequences contained within the NCBI sequence databases. The'Gl'identifier provides a uniform and stable naming convention whereby a specific sequence is assigned its unique G1 identifier. If a nucleotide or protein sequence changes, however, a new GI identifier is assigned, even if the accession number of the record remains unchanged. Thus GI identifiers provide a mechanism for identifying the exact sequence that was used or retrieved in a given search. a) Searches with toxin protein query sequences : The first step in the identification of toxin-antitoxin pairs was retrieval of toxin protein sequences (RelE, VapC, MazF, ParE, HigB, Doc, CcdB) from scientific publications. In this way, groups of experimentally verified toxin sequences of RelE, VapC, MazF, ParE, HigB, Doc and CcdB were generated. These se- quences comprise SEQ ID NO: 2,4, 6,8, 10,12, 14,16, 99,101, 103,105, 155, 160,221, 242, 259. The toxin sequences may be plasmid-encoded or chromo- some encoded./ b) Database searches for TA system components These toxin sequences were used as query sequences in data base searches as follows : The genomes of the organisms to be searched were downloaded from the NCBI ftp- server, ftp. ncbi. nih. gob/enomes/Bacteria. Then, the formatdb program, from NCBI blast suite, was used to create separately indexed databases (amino acid and nu-

cleotide or both) for each organism, to make them searchable with BLAST. As such the genomes of the organisms to be searched define the"search space". Plasmid DNA sequences were excluded from the search space.

The amino acid database created for each organism, were searched with programs BLASTP (matrix used: BLOSUM62), PSI-BLAST (matrix used: BLO- SUM62) and HMM-SEARCH (BLOSUM62) as described in the steps below. All other search parameters were default parameters as defined herein.

1. The groups of toxin sequences with SEQ ID : 2,4, 6,8, 10,12, 14,16, 99,101, 103,105, 155,160, 207,221, 242 and 259, were used as queries in a BLASTP search against the genomes downloaded from the NCBI web-site.

2. Score sequences ("hits") characterized by E-values lower than 10-1° were col- lected to generate the groups of"core sequences", with SEQ ID : 17-97,106- 154,161-205, 208-219,222-240, 243-257 and 260-263.

3. SEQ I D : 2,4, 6,8, 10,12, 14,16, 99,101, 103,105, 155,160, 207,221, 242 and 259, were used again in BLAST searches against the genomes searched.

Hits with an E-value lower than 1 were collected.

4. All the"hit"sequences from step 3 were then used as queries with the search programs described above and the 126 genomes as search space. Again, se- quences characterized by E-values lower than 1 were collected. This step was repeated until no further sequences could be added.

5. All sequences collected after step 4 were used as queries in a BLASTP search using the groups of core toxin sequences (SEQ 1D : 17-97,106-154, 161-205, 208-219,222-240, 243-257 and 260-263) generated in step 2 as the search space. Hits characterized by E-values lower than 1 were collected.

6. All the sequences retrieved in step 5 were sorted by size such that sequences of more than 160 aa and less than 50 aa were discarded.

7. The genes encoding all the collected toxin protein sequences were analyzed with respect to the presence of a closely linked upstream putative or annotated antitoxin gene of a suitable size (or, in the case of the Hig family of toxins, a pu- tative or annotated downstream antitoxin gene). Closely linked means that the distance (in bp) between the toxin and antitoxin genes was not more than 72 bp, or in one case, not more than 148 bp (ccdA and ccdB of Nitrosomonas eu- ropaeus). Suitable size of the antitoxin genes was not more than 140 and not less than 42 codons. The pair of GI numbers of the toxin and antitoxin protein sequences were then retrieved.

8. In cases in which there was no identifiable putative and annotated antitoxin gene sequence (in the form of a protein GI), the DNA flanking the toxin gene of inter- est was translated and inspected for the presence of a potential antitoxin gene.

Antitoxin genes found by this method were designated as"un-annotated".

Searches with toxin protein query sequences : Using the TBLASTN program provided at the NCBI web-site and default search pa- rameters, the toxin protein sequences collected as described above were used as query sequences in searches of the nucleotide sequences of interesting organisms.

This method provides a means to identify un-annotated toxin genes encoded by the DNA of an interesting organism. The cut-off E-value used in this analysis was also 10-4.

The results of the above-described searches are reproduced below, in Table 2. It is to be understood that the results shown are not intended to limit the scope of the invention in any way, but merely to illustrate methods for identifying homologues of the TA system components. In this particular search, 675 TA system homologues were found, in the following TA system families : relBE-159 vapBC-285 mazEF (or Chp)-67 parDE-59 higBA-74 phd/doc-26 ccdAB-5

The homologues found are reproduced below. Each toxin and it corresponding anti- toxin sequence has a separate GI number. In the nucleotide and protein sequences below, the first sequence codes for the antitoxin, and the second sequence codes for the toxin, except in the case of toxin-antitoxin pairs from the higBA family, wherein the first sequence is the toxin. Nucleotide sequences are presented first, followed by a section disclosing the corresponding polypeptide sequences.

In cases in which a toxin and/or an antitoxin homologue were found without an GI number assigned, the homologue sequence was defined by the Gi number of the DNA (chromosome) followed by a colon and"DNA co-ordinates"in the DNA of the gene (s). As in standard nomenclature known to those skilled in the art, a"c"in front of these DNA coordinates indicates that the gene of interest is encoded by the op- posite DNA strand.

It is clear to one skilled in the art that the nucleotide sequences described herein may be used in an artificial sequence comprised in a synthetic construct, which may be introduced into a suitable vehicle for production of the encoded polypeptide.

Table 2 Nucleotide sequences coding for homologs of vapBC toxin-antitoxin pairs

The sequences below were found in a later supplementary search:

GCTAAATCGGCGTTGCGTGCTGGCGAGATGTACCGCCGCTATCGTCAACGTAATGCCACC GAAAGTGACA TGAAATATTTTCTAGTTGGCGCTCATGCGTTGTTGCAGTGCGACGGCCTGATGACCTGGA ACGATGCGTT TTATCGTGACTATTTTAAAGGTATGAAACTCATCGTGCCAGGCGCATGA Nucleotide sequences coding for homologs of RelE toxin-antitoxin pairs 14600379 : 984865-985164, 14602207 >14602207_984480-985880_Aeropyrum_pernix. fna_2 [385-684] CTGTTAATTAGTGTATTTTTGATGCGGAGAGTCAGTGAGTGTGTTAGGTGGAAACTGTTA TTTAATCTCCATGTAACGTATTATATATTAGCAGACGGTGGTTTGATAGTGTCTTCGAAA AAGTCTAAGGTTAAGGTTGAAGTTGAGGTTGAAGTTCCCGAAGGCGATGATGAAGGCGTT TACAGGGAGGAATTTCGGAGAGAGCTAGCTAAGAGGATATTAAACGTAATGCTTGACAAG GACGTGGAGCCAGCTAAGCGGGCTGTTGCCAAGACTTTGCGCGAGAAGGGCGGGGAGGGA >gil14600379 : 985214-985498 TTGACAGAGGTCTATATAGAGAGTTCTGCAAAACGTGATTTAAAGAGGCTGCCAAAGCAT ATTGTCCAGT GGGTGTTAAACACTGTTGAGGAACTCGAGGAGAACCCGTTTATCGGCGAGAGGCTACATC TTCCAGCAAG CCTACATGGCTTGTACTGCTTTAAGCTAAGGCGAGGAGACTACCGGCTAGTCTACTGCTA CGTTCCAAAT CGAGACACAGTATATATCATCGCCGTTGGACACCGAGGCGAGATATACGAGAAGTTTCGA AGACGAATAA AATAA AATAA 15668172 : 840765-840947, 15669099 >15669099_840210-841610_Methanococcus_jannaschii. fna_2 [555-737] ATGAGCATCGTTCAATCTTATATTACTGATGAAAAAGGAAATATCAAAGGAGTTATTTTA GATTATAAGACATTTAAGAAAATTGAAGAGTTGTTATTGGATTATGGGCTTTTAAAGGCT ATGGAGGAAGTTGAGAATGAGGAAGAAATTGATTTAGAAACTGCTAAAAAGTTGTTAGAG CAG >gil15668172 : 840947-841222 GTGAAACAATGGAAGTATCTTTTAAAAAAATCTTTTATTAAAGATTTAAAGGAGTTACCT AAAAATATTC AAGAAAAGATTAAAAAATTAGTTTTTGAAGAGATTCCAAATAAAAATAATCCACCTGAAA TTCCCAATGT ALAAAAGCTARAAGGTGCAGATAGTTATTATCGAATTAGAGTTGGAGATTATAGAATTGG TTTTABATAT GAAAATGGAAAAATTGTGTTTTATAGAGTTCTACATAGAAAACAAATTTATAAAAGATTT CCATAA ------------------------------------------------------------ ------------------------ 15668172 : cl043988-1044146, 15669291 >15669291_1043000-1044400_Methanococcus_jannaschii. fna_ll [1146-988] (REVERSE SENSE) ATGAGGCTCAAAAAGAGATTTAAAAAATTTTTCATCAGCAGAAAAGAATATGAAAAGATT GAGGAAATTTTAGATATTGGCTTGGCTAAAGCTATGGAGGAAACAAAAGATGATGAATTA TTGACTTATGATGAAATAAAGGAATTATTGGGAGATAAA >gil15668172 : c1043988-1043722 ATGAAAGTGTTATTTGCTAAAACATTTGTTAAGGATTTAAAGCATGTTCCAGGGCATATA AGAAAAAGAA TAAAGCTAATAATTGAAGAATGTCAAAATTCTAACTCATTAAATGATTTAAAGTTAGATA TTAAGAAAAT AAAGGGCTATCACAATTATTATAGGATTAGAGTAGGAAATTATAGAATAGGTATTGAGGT TAATGGAGAT ACGATTATTTTTAGAAGAGTATTGCATAGAAAAAGCATATATGATTATTTCCCATAA ------------------------------------------------------------ -------- 20088899 : 1172771-1172992, 20089858 >20089858_1172220-1173620_Methanosarcina_acetivorans. fna_3 [551-772] ATAAATGCTATAATTGCTATAGTAACTATTATGTCAGAAACTACAACTATACAGATATCT AAAGACACCCGTGATGAGTTAAAAGCCATTGGGAAAATGGGGGATGACTACAATACAGTT ATACGAAAATTGATCCATGAACACAACTGCAATAAACTTATAGAAGAAGGCGATAGGCTC ATAAGAGAACATCGTGATGAGTTCGTGAGCATCGATGAGCTT >gil20088899 : 1172985-1173254 ATGAGCTTTAAAGTTCTGATCCACCCTAAGGTCTTCGAAAAGGTTCCTGTAGATCGTAGG GATCAAATAA AAGATGCCCTTCAAGAACTAAAAGACCCCTTGCCAGGGGGAAACAAAAAAGAAGTAAAAG GAAGTCACAA AACTGTCTATCGGCTTCGTATAGGCGATTTTCGTATTTTATACGAAATTGATTTTGAACG AAGCGAGGTT CTTGTTTTTAATATAATAACGGCTGAACAGGCGCATAAGAAGTACAACCGTTTTAAATAA 20088899 : c5035578-5035697, 20092909 >200929095034470-5035940Methanosarcinaacetivorans. fna17 [1227-1108] (REVERSE SENSE) ATGCAGCCCACGAACTTAAGCTTGAGCTGCTCGAAAAGATTCCGGAACTTGCAAAATACT GAGAATGAAGATCCTTCGGAAAGGGACCTGAATATTCGGATCCCCTTTCATATATATTAT >gil20088899 : c5035546-5035178 GTGATTGCCATGTCTAATATGGATGACGAACTCGAAGAAATCCGAAAGAGACGACTTGCA GAAATCCAGA GACAGCAGGCACAGCAACAGCCTTCCGACGTACAGGCAGCTTATCAGCAGGAGCAGGCAA GGGCTGAAAT GGAAGCTCAGAAACAAGCTATCCTGAGGCAGATCCTGACTCCTGAAGCAAGGGAACGCCT GACAACTCTT AAGATGTCAAGGCCGGCCCTTGGGGAACAGCTTGAGATGCAGCTTATTTCGCTTGCCCAG AGTGGAAGGC TCAAGGCTCAGATCGATGATGAGCAGCTGAAAACGCTCCTTATGCGGATGCAGCCTAAGA AACGCAAGAC GTCCATAACCCGGGTTTAA

------------------------------------------------------------ -------- 18976372 : c841447-841569, 18977239 >18977239_840420-841890_Pyrococcus_furiosus. fna-6 [1149-1027] (REVERSE SENSE) ATGTGGTTAATTTTTGCTCAAAATTATTGTCATAATAACAAATCTTTACGAAAAAGATAT ATTGTGGTAAATTTAACTTTCCTCCATGTCAAAAGTCATGGAGCTCTACAAGAAATATCT TGT >gil18976372 : c841484-841173 ATGTCAAAAGTCATGGAGCTCTACAAGAAATATCTTGTTGAAAGAGACCCACAACAAAAA TTAAAATTTG CAAAGGAAATTCTAGATAACTTGTTAACCCTACAGCTAAATCCCCCTATTTGGGAAACAA TAAGGAAGTC AACTGGACTAAAGGAGCACGAAATGAAAGAAATTCTTAATTATTTGGAGGAAAAGGGAGA AATTGAAATA AAGCGGGCAAAAGATGGAAAAAAGCTATATGCATCAACAATAAGAAGCATGAAAAGAAAA TCCAAGGAAA TACCCCTAGATATGTGGATCAGTAGGCACTAG TACCCCTAGATATGTGGATCAGTAGGCACTAG 23464628 : cl638570-1638836, cl638230-1638535 >Bifidobacteriumlongum1637860-1639190ll [1028-780] (REVERSE SENSE) CTGCCCCGAATGCAGACGCGAAGTGATGGCCGCGAAGGGCGAGGCGCTGCGCCTGTGCAG GTGCGGCAATCCCATCAACGTGCAGGAGCTGCGCGAGCAGAGCCGCGACAAGGCCGAGGC AATACACCTGACCAAGACACCGGCAGGCATGAGCCAATGGCTCAAGGGAAACTACGGGTA CGAGGTCAGCCGCAAGCGGATCAGCAACTGGCTCAACCGGGGCAAACTCCCCAGCTCGAG ACCCGTCGA >Bifidobacterium_longum_1637860-1639190_13 [675-370] (REVERSE SENSE) ATGGAAATCAAGCAATCCGCCGAATACCGCAAGTGGTTCAAGAAACTCAGGGACCACAAA GCGAAGGCCGCCATCCAAGCCCGGCTCGATGCCTGCAAGCTCGCAGGCAGGCCATTCGGC GACATCAAACCCGTGGGAGGCCCGGTCAGCGAGATGCGGTTCCACACCGGGGCCGGATAC CGCGTCTACTTCGCCATGCAGGGCAACGTGCTCATGCTGCTGCTCGCAGGCGGCGACAAA AGCACCCAGCAGACCGACATCAGACAAGCCCACGACATCCTCAACGACTACAAGGAACAA CGACAA 16124256 : 3371212-3371388, 16127361 >161273613370570-3372040Caulobactercrescentus. fna3 [642-818] ATGGCCGAGCCTGACCCCGACATCTTCGACGAGGACGATGAAGCGATCCTGGCGGCTGAC GCCGAGGCTGACGCCGACTTCGAAGCCGGTAGAACTGTTCCGCACGAGCGTGTGGGCGAG TGGCTCAAGACGTTGGGCACGCCGCACCAGACACCGCCACCATATTCGTGGCGCAAG >gil16124256 : 3371331-3371654 GTGGCTCAAGACGTTGGGCACGCCGCACCAGACACCGCCACCATATTCGTGGCGCAAGTA GTCTGGACCC AACGAGCGATGGCCGATGTTTACGCCATCGTCGGCCATATCTCCGAGCAGTCGCGTCCTC TCGCGGCCCA GCGCCTGGCCAAGAGGTTGTTCGACACCGGCGCTAGCCTGGCGACCTATCCCGAACGCGG GCGCGTGAGC ACTCAAGGACGGCGTGAGATCGTCGCGATTTCGCCCTACGTTCTGCGCTACCGCATTGTC GGCGACCGTG TCGTCATTGGCAGCGTACGCCATGGGGCGCGTCGACCTATCTAG TCGTCATTGGCAGCGTACGCCATGGGGCGCGTCGACCTATCTAG 17934719, 17933925 : c809573-809884 >gi17933925 : c810155-809874 ATGGCCAATGTGGAGAAGATCAGCGTTTCGATGACGCCGCAGCACGCCGAAATATTGCGG GATGCCGTGG AAAGCGGCGCTTACGCCAGCAGCAGCGAAGTCATCCGCGAAGCAATGCGGGACTGGTCGG CAAAATGGGT TCAGCGACGCAACGACATCACCAAGCTGCGCGCATTATGGAGTGAGGGCAAAGCCAGTGG CAATTCAACC GAAG >17933925 : c809573-809884 [1037-726] (REVERSE SENSE) ATCGTGACCACTAAGCTTGTCTGGACGCCCCGCGCACGCAGCGACGTGAAGAAAATCTAT GTCGATATCGGCAAGTCACAGCCTTTGGCTGCGGAGCGGTATTTTGCCCGTTTCCGCGCC AAAGCGGAGAGCCTGATCGACCATCCCCATCTTGGCGAACGCCATCCGGAAATTTTTCCG TCTGCCCGCATGCTCGTCGAAGCACCTTACGTCATTCTCTACGAAACCGTGCCGGATACG GATGACGACGAAATACGTTGCGTGGAAATCGTTCGTGTGAACGACGGTCGCCGGGACCTG CGGACACTGTTC CGGACACTGTTC 15963753 : cl588987-1588739, 15965227 >15965227 1587740-1589140 Sinorhizobium meliloti_1021_chromosome. fna_15 [1247-999] (REVERSE SENSE) CTGCGTCACCCACGAAATGGGCTTCGCCCGCCAGGTCGCCAACCGCGTGATCTTCATGGA CCAGGGCCAGATCGTCGAACAGAACTCGCCGGCCGAGTTCTTCGACAATCCTCAGCACGA GCGGACCAAGCTGTTCCTCAGCCAGATCCTGCACTGATCCGGAACAACTCGAAACGACGG CGGCCCGCCTTCATGGCGGGCCGTTTCGTTTTGTATTCCAAGCCAAAACCTCGCAGAAAC TCTCCATTC >gil15963753 : cl588729-1588451 TTGAGATTCGGGTACCGCCGCGGCCTCGAATTCCTGCCGTCTGCTCGAAAGGAATGGGAC AAGCTGGGCG CGACGATCCGGCAGCAGCTTGTAAAGAAGCTGCGTGAGCGTTTGGAGCGCCCCCGCATTC CGAGCGCCGC ACTACACGGGATGCCCGACCACTACAAAATCAAACTGAGACAGCTTGGCTATCGTCTCGT CTACCGGGTC GATGACGGCTCTGTCACTGTGCTGGTCGTGGCAGTTGGAAAGCGAGAGCGGGTGACGTCT ACAACTTGA 30248031 : cl478798-1479043, 30249331

>30249331-1477770-1479170_Nitrosomonas-europaea. fna15 [1273-1028] (REVERSE SENSE) ATTTATATGGCAATACTAAACGCAACAGAAGCAAGAGCGAGGTTGTACGCCTTAATTGAT GAGGCCGCAGAAACACACCAGCCTATTGTGATTAAGGGAAAAAGGTCAAGTGCGGTGCTT TTATCGGAGGAAGACTGGAACGCTATCAACGAGACGCTTTACTTGGTTTCTATCCCGGGA ATGCGCGAATCCATTATGGAGGGTATGAAAACTGATGTGGATGAGTGCAGTAGGGAATTG GATTGG >gil30248031 : cl478795-1478535 ATGTGGGAGCTGCGATATACCCATCAAGCGCAAAAGGATGCAAAAAAGCTGGCATCGTCT GGGCTTAAAG ATAAGGCAGAGGAGTTGTTAGCGGTTGTGAGGAATAATCCGTACCAAACCCCACCCCCCT ATGAAAAGCT GGTTGGTGATTTGGCTGGAGCCTGTTCACGCCGTATCAACATCCAGCACAGGCTCGTGTA TCAGGTGTTG GAGCGGGAGAGGATAGTAAAGGTTTTGCGTATGTGGACTCATTATGTGTAG ------------------------------------------------------------ -------- 16129958, 16127994 : 2087233-2087487 >gij16127994 : c2087762-2087484 ATGAACTGTACAAAAGAGGAGATTGACATGCGTACAATTAGCTACAGCGAAGCGCGTCAG AATTTGTCGG CAACAATGATGAAAGCCGTTGAAGATCATGCCCCGATCCTTATTACTCGTCAGAATGGAG AGGCTTGTGT TCTGATGTCACTCGAAGAATACAACTCGCTGGAAGAGACGGCTTATCTACTGCGCTCCCC CGCTAACGCC CGGAGATTGATGGACTCAATCGATAGCCTGAAATCAGGCAAAGGAACGGAAAAGGACATC ATTGAGTGA >16127994 : c2087233-2087487 [997-746] (REVERSE SENSE) GTGAAACTAATCTGGTCTGAGGAATCATGGGACGATTATCTGTACTGGCAGGAAACAGAT AAGCGAATTGTTAAAAAGATCAATGAACTTATCAAAGATACCCGCAGAACGCCATTTGAA GGTAAGGGGAAGCCAGAACCCCTGAAACATAATTTGTCAGGTTTCTGGTCCCGACGCATT ACAGAGGAGCACCGTCTGGTATACGCGGTTACCGACGATTCACTGCTCATTGCAGCATGT CGTTATCATTAT CGTTATCATTAT 15799931, 16445223 : c283932-284192 >gil16445223 : c284468-284208 ATGGCTGCTAACGCATTTGTTCGCGCCCGAATCGATGAAGATCTGAAGAATCAGGCGGCG GACGTACTGG CCGGGATGGGGCTGACCATCTCTGACCTGGTTCGCATAACCCTCACAAAGGTCGCGCGTG AAAAGGCATT GCCGTTTGATTTACGCGAGCCTAATCAATTAACCATTCAATCAATCAAAAACAGCGAAGC TGGCGTTGAT GTTCATAAGGCCAAAGACGCCGATGATTTATTTGATAAATTAGGAGTTTAA >16445223 : c283932-284192 [972-712] (REVERSE SENSE) ATATTGAACTCGGGACAATTTTCAAAGGATGTAAAACTTGCACAAAAGCGTCATAAGGAT ATGAATAAATTGAAATATCTTATGACGCTTCTTATCAATAATACTTTACCGCTTCCAGCT GTTTATAAAGACCACCCGCTGCAAGGTTCATGGAAAGGTTATCGCGATGCTCATGTCGAA CCGGACTGGATCCTGATTTACAAACTTACCGATAAACTTTTACGATTTGAGAGAACTGGA ACTCACGCGGCGCTCTTTGGG ACTCACGCGGCGCTCTTTGGG 30063468, 30061571 : c2077698-2077949 >gi130061571 : c2078973-2078701 ATGCGTACAATTAGCTACAGCGAAGCGCGTCAGAATTTGTCGGCAACAATGATGAAAGCC GTTGAAGATC ATGCCCCGATCCTCATTACTCGTCAGAATGGAGAGGCTTGTGTTCTGATGTCACTCGAAG AATACAATTC GCTGGAAGAGACGGCTTATCTACTGCGTTCCCCCGCTAACGCCCGGAGATTGATGGACTC AATCGATAGC CTGAAATCAGGCAAAGGAACGGAAAAGGACATTATTGAGTGGGTAATGCTGCCAACTTAC TGA >30061571 : c2077698-2077949 [979-728] (REVERSE SENSE) GTGAAACTAATCTGGTCTGAGGAATCATGGGATGATTATCTGTACTGGCAGGAAACAGAT AAGCGAATTGTTAAAAAGATCAATGAACTTATCAAAGATACCCGCAGAACACCATTTGAA GGTAAGGGGAAACCAGAACCCCTGAAACATAATTTGTCAGGTTTCTGGTCCCGACGCATT ACAGAGGAGCACCGTCTGGTATACGCGGTTACTGATGATTCACTGCTCATTGCAGCATGT CGTTATCATTAT CGTTATCATTAT >gil24473558 : 268650-268943 ATGACAGATAAAAAGCCGTTTGCTTTAAGTGAGGTTGCCCAAAGGGTTTTGATAGTCCTC GGAAGGGAAA ATAGGGGTCTAACTGTTAGAGAGTTAGTTGAAAAAACAGATACTAACAGTGGTAGTATCA AGAGAGCGTT GGAAGAACTTGCCAAACTTAACCTAATAAAGGAGGAAAAAGAAAACGTGTTTCCATATAG GAGGTTAATC AGTCTAACGGAGGTCGGAAGGGAAGTGGCTAAAAGAGTTATAGAAATAGAGGAATTAGTT AAGAAAGTGC AGTCAAATGGCTGA >gil24473558 : 268936-269223 ATGGCTGAAGAGTGGAAATTAGTATTCCATATCAAAATTAAGAGACTACCCAGGGAGTTC CAGAGTGATG AATTAGAGAGGATAGAAGAGGCTTTAGACAAGCTAAGTAAAATGGAATTAAATGAGCTTG ATATAAAGAA ACTGGAGGGTTGGAATGATAATGAAAACAGAGATATATTTAGGATAAGAGTAGGAAGGGA TATAAGAATT CTTGTCTCTTTCGATAACGAGAAAAAGCAAATTCATATATGGAGGATTGCTAGGAGGGAG TCTGTTTACG ATGAATAA ATGAATAA >gil11497621 : c977698-977510 ATGGAAGTCATTCAAATCTCAAAGGATGAGCTTGAAGAAATCATAGAGAGAAAATTCAAG GAAGTCCTGA TTAAGGCTTTGATGGAAATTACTCCTTACGTTTCCGATGAAGAGCAAGAAGAAATCGATA AGATAGCTGG AAAGCCTGATGAATACGAAGGTGAATTTGAAGAATGGCATGGAAAGTGA

The following sequences were found in a later supplementary search:

Nucleotide sequences coding for homoloas of Phd-doc toxin-antitoxin pairs 24473558 : 1143830-1143531, 15921403 >15921403_1142330-1143870_Sulfolobus_tokodaii. fna_10 [1500-1201] (REVERSE SENSE) ATTAATTCGATATTCTTTGCTCTCTTAATAAAAATATATTTAATTATATTCGATATTATA AAATATATATGGTTTTATTTGAATGGTACTGGTTTTGCTCAATTTTGGCTAATGTTATTA GTCTCAGAAAAAAGAGATTCCCATACTGACTTAAACAAACTATTAGAAATCATTCATCAT AATTTTAGGAAACATTTACAAGAAATAGACTTAGCTAAGTGTTATAAACGAATAAAGAAC TTTATAACTAGTAGTCTTAAGTATAAGAACAAGCTATGTAGTTTAATAGTAGTTAACACT >gil24473558 : c1143514-1143056 ATGGAGAACAAGTTAATGCAAATCTTGGAAGGATTATTAAACGAATTCGAAAAATGGAGA AGTAGAGAAA GCGATAGAGTACCAACTATAATACAAATCCACGATAGTATAACCAGAAATGATCCTAATA CAGAACGTGG TATAGTCAACTTAGATACTATAGGTATTACAATATATTCTGCAATTGAGAACCTTAGTCT TTATCATGAT ATTAGTAGGAGTTTAGCAGTGTTAACATATCGTTTAATAACTTCCCATCCGTTCGTTGAT GCGAATAAGA GAACGGCCTTCGTATTATTGTTAGACATCTTATATGAATTATTTGACAAGGAAATTCCTC AAGATTTAGA AGAAGAATTGATAAAGACCTTAGCTGAAGTAGCCGATAATCCGCCGGAAGAAGACGAGTA TGCAATAAAC AAAATAAGAGAAACTATACGGCAGATTATTGAAGGTTAA AAAATAAGAGAAACTATACGGCAGATTATTGAAGGTTAA 28209834 : c2057481-2057179, 28211562 >28211562 2056040-2057580_Clostridium tetani_E88. fna_10 [1441-1139] (REVERSE SENSE) ATAATTTTAGGTTTAATTTATCCTAAAATTGTGTATAATATAACTATAGAGGAGGTGCTT TTTATGCAAGTAAATATTAATAATTTAGTATCCATATCAGAGGCTAATCAAAATTTTTCT AGAGTTGCAAGAATGGTAGATGAAAATGGTGCAGCTATTATATTAAAGAATAATGCACCA AGATATGTCTTAATAGACTATAGTAAATTTCAGCAAGATACTATTGCAGATGATGCTACA GTAGAAGAAGCTGCAAATAATATTTTAAATAAACATCTAAAAGCATTTGAGGAGTTGGCT AAA >gil28209834 : c2057179-2056796 ATGAAACACCTAAGTAAGGAACAAATGATGTATCTACATTCTATGGCAGTTAAAAAGACC GGCGGATTAG ATGGGATAAGAGATGAAGGATTGTTAGATTCAGCTTTAAATTCTCCATTTCAGTCATTTG CAGGTGAAGA ACTATATCCATCTATACAAGCTAAAGCAGCAAGATTAGGATTTAGTATTATTAAGAACCA TCCCTTCTTA GATGGAAACAAAAGAATAGGAATGCTAGCAATGATGGTGTTTTTAGAAATTAACGGAATT CAATTGGAAT GTAGTGATGAAGATATTGTAGATATTGGATTGGGCATAGCATCAGGTAAGTATGAAGATG ACTATATTAT AGATTGGATTATTAGTTGTAGTAATAATAGTTAA 16124256 : c3613552-3613915, 16127593 >16127593_3612420-3613960_Caulobacter_crescentus. fna_14 [1494-1132] (REVERSE SENSE) ATAGCCTTCGAGGAAGGCTTCGAGTTCCTGGTCGGTGATGTCGGTATAGACGGCCATGAC GCGGGGATGCGGGAGCGGGCGCTGGCGGTCAAGGGGGCGGTGAGGTATAACGTTTGTTCT AACGTTTGGAGCGCCGCCATGATCGCCCTGAAACTGTCCCAGATCGGCAACTCCGTCGGT GTGGTTTTGCCGAAGGAAGCGCTCGTCAAGCTCGGGGTCGAAAAGGGTGACACGCTCTAT CTGACCGATGCGCCGGGTGGCGGCATGCAGATCGCGCCCTACGACCCGGACGTGGCGCGA CAGATCGCGTTGGGCGAGGAGATCATGGACGAGTATCGCGACACGTTCAGAGCGCTGGCC AAA >gil16124256 : c3613552-3613160 ATGAGCGGTGTCGGCGAGCCCGTCTGGGTTCGTATCGAGGCGCTCAAGGTGCTTCATGAG CGCAGCTTGG CGCTTCATGGAGGGCCGTCCGGTGTGCGCGATGAAGGCCTTCTGGAGTCCGCCCTGGAGC GGCCCAAGAA TCGTTTCCACTACGAGGGCGTCGACGATGTCGTCGAACTCGCGGCGACCTACGCCGTCGC GGTTTCGAGC AATCACCCCTTCGTCGACGGCAACAAGCGCGCGGCCTTTCACGCGATGACGCTGTTTCTT CGTCTGAATG GCCTACGGCTCGTTGCGGATCAGGCAGACGCTGCGCGGACGATCTTCAAGCTCGCCGCCG GGGAACTCGA CATTCCAGCTTTGACCGATTGGTTGAGAACCCGTGTCGCTTGA 15675948 : c929475-929630, 15676812 >15676812928340-929880NeisseriameningitidisMC58. fna18 [1290-1135] (REVERSE SENSE) ATGCCCGCAAACAGACAAGGAGCAGCGATGCAAAACCAAAATACACGCCCCGTCAAAATC GAGCTTAAAGGCGAAGCAGGCAAACGCGTACTGCTTGCCGCCGCCCGCCGCATTGCCAAA ACCCATCAAAAAGCCGTCAAGGCACTTGCCGACAAA >gi15675948 : c929475-929107

ATGATAGACGGCGAACTGGTCGCGCTTATCCATCAAACCGTATTGGCGGATGAAGCGGGT TTGAAAGGGC GGGCGGATATGGCGCGCTTGGACGGCGCATTGTCGCGGATTGCCAACTGGCGGCAGTATG AAAACCTTGA GGACATCTACGAAATCGCCGCCCTCTATGCACAAGCCATAGCCAAAGCCCACGCCTTTCC CGACGGCAAC AAGCGCACCGCGCTTTTAACAATGTTGACCTATCTGGATTTGCAGGGCATCAGCATTGCC GCCGACCAAG GGCTTGACGACTTGATTGTCAGTTTGGCGGCGGGAGAAACCGACTTCAAACAGCTCGCCG AAACCCTGCG CCGGCTGGATAAGGAATAG CCGGCTGGATAAGGAATAG 30248031 : cl386501-1386749, 30249247 >30249247_1385370-1386910_Nitrosomonas_europaea. fna_12 [1379-1131] (REVERSE SENSE) TTGGTTATAACATTAGGATATGAGATGATTGAGTTGAAAGTCAGAAAGTTTGGCAATTCT CTTGGCATTGTTTTGCCAAAAGAAGTAGTTAACCATTTACGCACTGGGGATGGGCAACGG TTGTTTTTAACCGAAGCATCTGATGGAAGGTATCTTATTACACCATACGATCCTTCATTC GGCGAAAAAATGGCAAAGGTAGAAGATATATGTAATCGGTACCGTAACACGCTCCATGTA CTGACCAAG >gil30248031 : cl386501-1386112 GTGACAACGCCTGTCTGGATAAACGAACAAGATGTCCTTGCCATTCATGAGCGTTTAATT TTTCTGCATG GCGGTGCATCAGGTATTCGTGACAGGAATCTTCTGAAATCAGCACTTGCAAGACCGCTCA ATTTTTCTGT CTACGATCAGCAGTCTGATATTTTCCTTTTGGCTGCTACTTACACAAGCGGAATTCTGCA AAACCACCCT TTTGTGGATGGGAACAAACGGACAGGATTTGTAATTGGCGTACTATTTCTTGAACTCAAT GGCTACAAGT TTATCGCTAACGAAGAAGATTCAGCACAAGCCATAATTTCGCTTGCTGAAGGCTCTCTTG ACGAGCTTGG ATTCAGATTGTTCATTGAACATAACTCAATTGCAACGTAA ATTCAGATTGTTCATTGAACATAACTCAATTGCAACGTAA 30248031 : 2674530-2674754, 30250372 >30250372_2674000-2675540_Nitrosomonas_europaea. fna_6 [530-754] ATGGTTGAGCTGAAAGTCAGAAAATTAGGTAATTCCCTGGGAGTTGTGCTGCCCAAAGAG GTCATTAACCATTTACGTACCGGAGATGGACAGCGGCTGTTTTTGACCGAGGCGTCCGAT GGCGGGTATTTGATTACCCCATACGATCCTGCTTTCGAAGAAAAAATGGTCAAGGTTGAG AATATTTGTGACCGTTACCGCAATACGCTTCGTATACTGGCTAAA >gil30248031 : 2674754-2675143 ATGATCGAGCCGATCTGGATAGATGAGCAGGTCGCGCTTGCTATTCATGAACGCCTGATT TCTCTACATA GCGGTGCATCAGGGGTTCGCGACAAAGAGCTTCTGAAATCGGCCCTTGCCAGACCTCTCA ATCTTCTGGC CTATGATCAGCAAGCAGATGTTATCCATCTAGCTGCTGCATATACCGCCGGGATTTTGCA AAATCATCCT TTTGTGGATAGAAACAAACGAACGGGTTTTGTCGTCGGAGTACTGTTTCTTGAGCTTAAT GGTTACAGAT TTACTGCCGCTGAGGAAGACTCTGCGCAGGCAGTAATTGCGCTCGCTGCAGGTTCTCTTG ATGAAGCCAG GTTCAAATTATTTCTTGCGGATAATTCGATACCTGTCTGA 22123922 : c2738578-2738880, 22126357 >221263572737350-2738960YersiniapestisKIMchromosome. fna12 [1530-1228] (RE- VERSE SENSE) ATGCAGTTGATTAGATATAGCTTGAGCTATACACTATGTATCAACAAGAATGGTTACAAC CCATTCACAACTGCTGAAAATTCAATGTGTCAGCGGTTTTCTATCTATAATTCAGAGGAT AACGTAATGAGCCATGCACTGAAAAATGCAGATCGCTTATACATTCCACCTCGTGACAAG GGCACGAAGGCCTATCCACGTGCATCTATGGATACAAGTAGCACTCATGCAGATCAGGTC AAAAATGCATTTGCGTTTGGCTTTTCTCGCTATGAAAAAGCAATGGAAGAACTTTCTAAG GTG >gil22123922 : c2738564-2738088 ATGGCAGATATTGTTGAAGGGATACATTATCTTTCTGTTGAAGATTTCATCTACATAAAC AGAACGTTAA TTGAGGCTCAAACCCCTAGCGAGCCAATTGATGTCATTAATCACAACAATCTCTGTTCCT CACAAGCAAG ACCCAGCGTAGTAAAATACTATCAGCAGACAGACGATATGTTCGAACTGTCTGCTGCTCT CATCGAGAGC TTAATCCAGAATCACGCCTTTGCAAATGCTAACAAACGAACAGCTATGATGGCTGGATAT ATGTTTTTGT TGCTTAACGGATATGAACTCACTGCACCTGGCGACGAGATTGTGGTAATGGCAGAGGGGA TGGCCAGAAA GGTTTATAACTGCGAAGACCTAGAGAATTGGCTCTGCTACTGGTCTAGGCCGTATGACTC ACGAAACTTA TGTGATTGTGAGATATCTTCTCTAGTAGTGACTGCAACACAGGTAAAGATAGAATAA ------------------------------------------------------------ ------------- 15595198 : 69056-69187, 15595251 >15595251_68530-69930_Pseudomonas_aeruginosa. fna_7 [526-657] ATGTCGCAAGACCAGCAAGGGATACGCTATCTCTCCGTTGCAGATCTCGTTCGCCTCAAT GAGTTGCTCATCCTGGCCCAGACTCCGGACGAGCCGATAGGCGTCCTCAAACCGAACGAG TTGGAGTCCGCA

The following sequences were found in a later supplementary search:

CCTTTAGGAAGCTAATAGAACTTACTAAGAGTTCAACAAGTCCAGTAAAAAATGCCATTG ACAGCCTTGA AGAGAAGGGACTTGTTGAAGAGATTGAAGAGACTGAGAGCTTCCCTAAGAGGAGGTATAT CAAATTGACA GAAAAAGGTAAAAAGGTAGCCGAGAAACTTAAAGAGTTATATACGTTGATAGAGTCTACT TCATAA Nucleotide sequences coding for homologs of HigBA toxin-antitoxin pairs 23308765 : 1085714-1086001, 1085499-1085777 >CorynebacteriunLglutamicumATCC13032. fna\1085000-10864004 [714-1001] GTGGCGGATCTGCTTCCGTTGGAACGACTCGGGCCCCGAAAACGTCGAGATCGTGGATTA TCACTGAGGAGGAGACGATGGCTCAGAAGCTCTACCCGCCGATTCACCCTGGTGAGATTC TCATGGAGGACTTCATCAAGGGCTTCGGCCTCACACAGAACAAGGTCGCCGTATCGATCG GGGTGCCTCCGCGACGCATCAACGAGATCGTGCACGGCAAGCGATCCATCACGGCCGATA CGGCTCTGCGTCTCGGGCGGTACTTCGGTATCGACCCGCAGTTCTGGC >Corynebacterium_glutamicum ATCC_13032. fna\_1085000-1086400_3 [499-777] GTGATCAGATCGTTCGCCGACCGCGACACCGAGTTGGTCTGGTTGCGTGAAGGTGCGAAA CGCGTCGATCCGCGAATACACAAAGTGGCGAATCGGAAGCTGCATCTGCTGGACGCGGCG ACGACCCTCGATGCTCTGCGTGTGACTCCGGGGAATCGCCTGGAAACGCTCGAGGGTGAT CGAGTCGGTCAGTACAGCATTCGAGTCAACGACCAGTGGCGGATCTGCTTCCGTTGGAAC GACTCGGGCCCCGAAAACGTCGAGATCGTGGATTATCAC 15836605 : cl629883-1630197, 15838310 >15838310_1628830-1630230_Xylella_fastidiosa_chromosome. fna_15 [1367-1053] (REVERSE SENSE) CTGATTCGGTGTAGTGGTACATGTTCAGTACGAAAAACCTTTTTTAGCGGTCAAATTAAG GTGCCGGTAGAGGCGCTGCTCCAGCGCCTCGCGGGTGGAGCGGCCTCAATGGCCCCGCGT CCGGCAAGGATTAAGATGCCGCATGAAGCGGAACGGTGGTATCAGAAAATGCCGCAACGC GATGTAAGGGTTTTGGTAGGCACTGATACCCGCACGACTTCCTATTTTGATCATCAATCT CTCAATCTTGGAAGGGATAGGTGTCGCTTGAAATCAAATATCATCACTATTACCCTTAGT GTAATAGTGGTATAT >gil15836605 : cl629865-1629575 ATGGAAGTCAAGTTTGAAGATCCATCGTTGGAGCGACTGGAAGCAAACCAGAAATACACT GCTGGCTTGG TCAAGGTGTTCCACCGGCGCATACAGTTCATCAGGGCATCGCCTGACGAACGTGCGTTCT ATGCCATGAA ATCACTGCACTACGAAAAACTCAAAGATGATCCGGACAACCTGTACTCCATGCACCTAAA CGACCAATGG CACCTGATCATGTACCTAAAAGCAAAAGAAGATGACACAAGAAATCTAGTCGTCATTGTT TCAATTGTCG ATTACCACTGA 15599869, 15595198 : c5242573-5242848 >Pseudomonas_aeruginosa. fna\_5241810-5243210_18 [1038-763] (REVERSE SENSE) ATGATTCTGACCTTTCGCTGCGACGAGACTCGTCAGCTTTTTGAGACGGGTCTTTCGAGG CGGTGGGGAGCGATCCTCACAGTCGCTACGCGTAAGCTCGCAATGCTTCATGCGGCTACG GAGCTTCGAGACCTGCGCTCTCCACCTGGAAACCGGTTGGAGCCGTTGCAGGGAAAGCGG GCGGGCCAACATAGCATCAGGATCAATGACCAGTGGCGTGTCTGTTTCGTCTGGACGGAT GCGGGTCCCGAAGAAGTCGAAATAGTTGATTACCAC >gil15595198 : c5242558-5242253 ATGGCTACCAATGGTATGCGCCCCATCCATCCTGGGGAAATATTGCGCGATGAGTTTCTG ATGGAGTTTG ATATCTCTCCAGCTGCTCTAGCACGCGCTTTGAAAGTCTCCGCTCCGACAGTGAACGATA TCGTTCGTGA GCAGCGTGGTATCTCCGCAGATATGGCGATTCGTCTGGGGCGTTACTTTGATACGTCCGC TCAGTTCTGG ATGAATCTCCAGAGTGAGTATTCGTTAGCAACTGCTTATGCGGCGAATGGCAAGCAGATC GAACATGAGA TTGAGCCGCTGCTTGCTCACGGATAG >gil2l226102 : 674599-674877 ATGGCAGAGGCATTAAATTCTGATAAGATAAAACGTTCTCCAACTCTTAACACTATTATT ATGGTAGAAG ATGCTATACAAAACAGCCCAAATAGTGTTATAACTATTCCGGAACTAAAAAAAGCGCTTC CTCGACAGGT AAACCACAATACTTTAATGACTATTTTGGAATACCTGGAAAAAAGTAATAAAATAGCTGT TGGGTTAAGA GGGATAACCTGGATTCACAACACAAATCATAATTTAAGGAATGTTGCGATTTACGGGCGC GAGCTATAA >gil21226102 : 674890-675240 ATGAAGCGTGTAAGTGTAAGATTAACTCCCGAAGCTGATGAGGCATACGAATATCTGATA AGTAAGGCTT CGGACTCAAAGCAGGAAGAGACAATTCTTAATGCTTTTCATCAGAAAATAGAGTTAATAA AAAACGATGT TCATTATGGAAATCCAGTTGCTAAAAGATTAATTCCTTCAGAATATAAAACCAAATATGG AGTAAATAAC CTGTTTAGAGTGGAACTCCCAGGCTTCTGGAGAATGCTTTACACACTTACAGCTGGTAAT TCGGGCGTTG AAACTCTCGTAATAGTGATTGATATAATCGATCATAAAAAATACGATAAAGCATTTGGTT ACAAGAAGTA A A >gil17227497 : c3563263-3562970 ATGGCACGCCCACCAATCCACCCCGGAGAAATTCTTGCTGACGAAATTACTGAACTCGCT ATGACTGCGA GTGATTTAGCGCGTGTTCTCCATGTTCCCAAAAACAGAATTACTGAAATCATTAATGGCA GACGAGGGAT AACAGCCGATACAGCTTTGCGATTAGGACAATATTTTGGAACTGGTGGAGAATTCTGGTT AAATCTTCAA

The following sequences were found in a later supplementary search:

>gì|22123922 : 2218967-2219290 ATGAAAAAAACAGACGATTTTGACATCATTCCTTTTGCGGTGGTTAAAGCAGCAGCGTTG AGTCATCCGC AGGTGAATGACGCCTATACGGATTTACAAATTCGGCAAGCGATGATGACTGAACTGAAAG CGGCCCGCCA ACAATGCAATTTGACTCAAGAAGAGGTCGCACTGCGGGCGGGGCTGAAAAAACAAAATAT CAGTCGTATG GAGAAAGGCATCATTTCACCTAACCTCACCACCTTGAGCCGTTATGCCGCAGCACTAGGA GGGACTTTCG TTTTTCAATTCAACCCAAACTCATCTTATGCGACTAAGGAGTAA >gil22123922 : 2218967-2219290 ATGAAAAAAACAGACGATTTTGACATCATTCCTTTTGCGGTGGTTAAAGCAGCAGCGTTG AGTCATCCGC AGGTGAATGACGCCTATACGGATTTACAAATTCGGCAAGCGATGATGACTGAACTGAAAG CGGCCCGCCA ACAATGCAATTTGACTCAAGAAGAGGTCGCACTGCGGGCGGGGCTGAAAAAACAAAATAT CAGTCGTATG GAGAAAGGCATCATTTCACCTAACCTCACCACCTTGAGCCGTTATGCCGCAGCACTAGGA GGGACTTTCG TTTTTCAATTCAACCCAAACTCATCTTATGCGACTAAGGAGTAA TTTTTCAATTCAACCCAAACTCATCTTATGCGACTAAGGAGTAA >gil22123922 : c3594411-3594262 TTGGATAATAAACGCCAACCACCAAGCCTGTCCCATGAACAAGTGGTCGCCCGAATGCTA AAGAAACCGG CAGTGAGGGCAGAATATGAGCGGCTGGAGCGCCAGGATTTCGCCATCATTGATGAAACGT TAAAGGGAAT ACATTCCGAATAA >gil22123922 : c3594411-3594262 TTGGATAATAAACGCCAACCACCAAGCCTGTCCCATGAACAAGTGGTCGCCCGAATGCTA AAGAAACCGG CAGTGAGGGCAGAATATGAGCGGCTGGAGCGCCAGGATTTCGCCATCATTGATGAAACGT TAAAGGGAAT ACATTCCGAATAA Nucleotide sequences coding for homologs of ParE toxin-antitoxin pairs 16124256 : c2971288-2971506, 16126988 >16126988_2970240-2971640_Caulobacter_crescentus. fna_13 [1266-1048] (REVERSE SENSE) ATCATGAACAAGCCTGCCAAGCCTGCGGCGGATGACGTCGACGACCTCTTTGGCCGCCCG CTGACGCCGGCCGAAGAGGACACATGGTTCGAACATAATCGCGAAGCCATCGGTCAACTC GTCGATGAGGCTTGGGCTGAGTTCGAGCGTGGCGAATATGACGAACGCAGCTTCGCTGAG ATCATCGCGCAGGGCGTTGCAGAGCATAACGCCAAACGC >gil16124256 : c2971272-2970970 GTGGGGCGCGTCATTAGGACCCGGCCGGTCAGTGGCGACCTTGACCGTGTTTTCAGGGAT GTTTGTGAGA ACAATGGCGTCAAAGTCGCGAGCGCTCAGTTGAACCGTATAGAGAGCGTGTTTCACCGCT TGAGCGCATT TCCCAGACTGGGTCGCGATCGGTCGGATTTGAGGCCAGGATTGCGGACCTTTTCCGTAAA GCCCTGGCAG GTGCTCTATCGACTGAATGGTGAGGATGTCGTCATTCTCCGCATCCTCGATGGCCGCATG AACCTCGCCG CCCAATTGGGCAAGAAGACCTAA CCCAATTGGGCAAGAAGACCTAA 15595198 : 796960-797238, 15595926 >15595926796530-798000Pseudomonasaeruginosa. fna6 [430-708] GTGTTCCCACAGCAATGGAGGTACCGGCTCATGCGAGTCGAGACAATTAGTTATTTGAAA CGTCATGCGGCTGACCTGGATTTATCCGAGCCAATGGTCGTCACGCAGAACGGTGTTCCT GCCTATGTGGTTGAGTCATATGCTGAGCGGAAGCAGCGCGATGAAGCAATTGCGCTGGTG AAGTTGCTTGCGATTGGCTCCCGCCAGTACGCAGAAGGCAAGCATCGCTCTGTTGATGAT TTGAAAGCTCGCCTTTCCAGGAGGTTCGCTCAGCCAGAA >gil15595198 : 797251-797598 ATGTCCCCGGTCGTCATTCGTTTTACTGATACCGCAGAGCAAAGCATCGAAGACCAAGTC CACCACTTGG CTCCATTCCAAGGTGAACAGGCTGCACTCCAGTCAGTACTGAGCCTTTTGGATGAGATTG AAGAGAAGAT TTCACTTGCACCTAAAGGTTACCCAGTCAGCCAGCAGGCGAGTCTTCTGGGGGTGCTGAG CTATCGCGAG CTTAATACCGGCCCCTATCGTGTTTTTTACGAATTCCACGAAGAGCAAGGCGAGGTGGCA GTGATCTTGG TTTTGCGACAGAAGCAGAGCGTTGAGCAGCAATTGATCCGCTACTGCTTGGTGGGGCCAA TCGAGTGA >gi15607142 c2204223-2203972 ___________________________________________ >gil15607142 : c2204223-2203972 GTGGGTAAGAACACGTCCTTCGTCCTCGACGAGCACTACAGCGCCTTCATCGACGGCGAG ATCGCCGCGG GCCGCTACCGGTCGGCCAGTGAAGTCATCCGCTCCGCGTTGCGACTGCTCGAGGACCGTG AAACCCAGCT GCGCGCGCTTCGTGAGGCTCTCGAGGCCGGCGAACGCAGCGGCAGCTCGACACCGTTCGA CTTCGACGGA TTCCTCGGTCGTAAGCGGGCTGACGCCTCGCGTGGCCGGTGA >gil15607142 : c2203975-2203679 GTGAGTAGCCGATACCTTCTCTCGCCTGCCGCGCAGGCACATCTGGAAGAGATCTGGGAC TGCACCTATG ACCGTTGGGGTGTCGATCAGGCCGAGCAGTACCTGCGCGAACTTCAACACGCTATCGACC GTGCTGCGGC AAACCCGCGGATCGGACGAGCGTGCGACGAGATTCGCCCCGGCTATCGCAAGCTCTCGGC CGGGTCACAC ACGTTGTTCTATCGGGTGACTGGCGAAGGCACCATCGACGTCGTGCGAGTCCTGCACCAA CGGATGGACG TCGACCGGAACCTCTGA

The following sequences were found in a later supplementary search:

Nucleotide sequences coding for homologs of Chp toxin-antitoxin pairs 15607142 : 3110734-3110507, 15609938 >15609938-3109400-3110940_Mycobacterium-tuberculosis-H37R v. fna_14 [1334-1107] (RE- VERSE SENSE) GTGAAGTTGAGCGTGAGCCTGTCCGATGACGACGTCGCGATCCTGGACGCATATGTGAAA CGAGCGGGATTACCATCCCGCTCCGCCGGCCTGCAGCATGCGATCCGCGTGCTTCGCTAC CCCACGCTCGAAGATGACTATGCCAACGCATGGCAAGAATGGTCGGCAGCCGGCGACACG GACGCGTGGGAGCAGACCGTCGGCGACGGAGTCGGTGATGCGCCGCGG >gil15607142 : c3110520-3110164 GTGATGCGCCGCGGTGAGATTTGGCAGGTCGATCTCGACCCCGCTCGAGGTAGCGAAGCG AACAACCAGC GCCCCGCCGTCGTCGTCAGCAACGACCGGGCCAACGCGACCGCCACGCGTCTTGGGCGCG GCGTCATCAC CGTCGTGCCGGTGACGAGCAACATCGCCAAGGTCTATCCGTTTCAGGTGTTGTTGTCGGC CACCACTACT GGTCTCCAGGTCGACTGCAAGGCGCAGGCCGAGCAAATCAGATCGATTGCTACCGAGCGG TTGCTCCGGC CAATCGGCCGAGTTTCAGCCGCCGAACTTGCCCAGCTCGATGAGGCTTTGAAACTGCATC TCGACTTATG GTCGTAG GTCGTAG 15607142 : c2234644-2234919, 15609128 >15609128 2233560-2235030_Mycobacterium tuberculosis_H37Rv. fna_18 [1359-1084] (RE- VERSE SENSE) CTGGAAGTTATACCCGGTTATACTATCTGTATGAAGACAGCTATTTCTCTGCCGGATGAG ACGTTCGATCGGGTATCGCGGCGTGCGAGTGAGCTCGGCATGAGTCGGTCCGAGTTCTTC ACGAAGGCTGCGCAGCGCTACCTGCACGAGCTGGACGCCCAATTGCTCACGGGCCAGATC GACAGGGCTCTAGAGAGCATCCATGGCACCGACGAAGCGGAGGCCCTCGCCGTGGCCAAC GCATACCGCGTGCTAGAAACCATGGACGATGAGTGG >gi] 15607142 : c2234647-2234303 GTGGTGATTAGTCGTGCCGAGATCTACTGGGCTGACCTCGGGCCGCCATCAGGCAGTCAG CCGGCGAAGC GCCGCCCGGTGCTCGTAATCCAGTCAGATCCGTACAACGCAAGTCGCCTTGCCACTGTGA TCGCAGCGGT GATCACGTCCAATACGGCGCTGGCGGCAATGCCCGGCAACGTGTTCTTGCCCGCGACCAC AACGCGACTG CCACGTGACTCGGTCGTCAACGTCACGGCGATTGTCACGCTCAACAAGACTGACCTCACC GACCGAGTTG GGGAGGTGCCAGCGAGCTTGATGCACGAGGTTGACCGAGGACTTCGTCGCGTACTGGACC TTTGA 15607142 : 2547085-2546840, 15609411 >15609411_2545760-2547160_Mycobacterium_tuberculosis H37Rv. fna_14 [1325-1080] (RE- VERSE SENSE) ATGGCCGAACCAGAAACCCTTCCTGGGCGGTGGCTTCCGGAATGCGCCTGCCTAGCTGAA ACCGTGAGTTGGGAGCAGAGTCGTCTCTGGTCCCGCCTGTTATGCCGTCCGCATTTTCGT CATGCGCTGCCGGGGCTGACCGGGGGCTCTGCAAGTCGTCCGTCGGCGAGATCAGCACGC CTGGTTCGGCAGCCACGTATGACATTGTTTTCCTTGGACCATAGGGACGGGGTCGACGCT CGGTGT >gil15607142 : c2546803-2546486 ATGTCTATCGCCCGATCGGCCCAGCCTATTGGGTGGATCTCGTGTCCACCAAAAGGGGGA TCCAGCTGCT GCCGCTGTGGCGGCGGGTACACTCACATATTTTGCGTATCAGCCTGGACCGGTCTTGTGG TTGACTTGCA GGCTGAGCAGGTCAGATCCGTTGTGACCGAACGGCTGCGCCGGCGGATCGGCCGAGGCGC TCCTATCCTC GCAGGCACGCTGGCTCCCGGCGTTGGTCTAGCCGCACAAAATCGTGAATTCCGGCAATTT ACAGGAAGGT CCGCGCCGCCATCGGCCACGATCGCATTTGGCGAGTAG CCGCGCCGCCATCGGCCACGATCGCATTTGGCGAGTAG 15839372 : 3105455-3105228, 15842339 >15842339_3104150-3105620_Mycobacterium_tuberculosis_CDC1 551. fna_14 [1305-1078] (REVERSE SENSE) GTGAAGTTGAGCGTGAGCCTGTCCGATGACGACGTCGCGATCCTGGACGCATATGTGAAA CGAGCGGGATTACCATCCCGCTCCGCCGGCCTGCAGCATGCGATCCGCGTGCTTCGCTAC CCCACGCTCGAAGATGACTATGCCAACGCATGGCAAGAATGGTCGGCAGCCGGCGACACG GACGCGTGGGAGCAGACCGTCGGCGACGGAGTCGGTGATGCGCCGCGG >gil15839372 : c3105238-3104885 ATGCGCCGCGGTGAGATTTGGCAGGTCGATCTCGACCCCGCTCGAGGTAGCGAAGCGAAC AACCAGCGCC CCGCCGTCGTCGTCAGCAACGACCGGGCCAACGCGACCGCCACGCGTCTTGGGCGCGGCG TCATCACCGT CGTGCCGGTGACGAGCAACATCGCCAAGGTCTATCCGTTTCAGGTGTTGTTGTCGGCCAC CACTACTGGT CTCCAGGTCGACTGCAAGGCGCAGGCCGAGCAAATCAGATCGATTGCTACCGAGCGGTTG CTCCGGCCAA TCGGCCGAGTTTCAGCCGCCGAACTTGCCCAGCTCGATGAGGCTTTGAAACTGCATCTCG ACTTATGGTC GTAG GTAG 21672841 : 947841-948164, 21673827

>21673827-947380-948850-Chlorobium-tepidum-T5S. fna-2 [461-784] CTGCTCTTGGAAGGCAGTATCGGTCTGTTGCCGGATGCTTTGTTGAATAATGAAGAACCA GAACAGAATACGGGTTACAACAGTTCAGCTCGATGTATTGTCAATCGTGAGGATCAGGCA GGAATCACGAGAAAAGAGACTATCGGTGCTTCGGTATGGTTTGGGCTGGTATGTGTCACA GATGAATCTGTCGCTTATAGGTATGATGGTTTGGCGGCACGATCGCTGAGGTTATGGACT ACGCCTTCCTTGAAGAAGCAGCAGATCGCGAAGGCTGGAACGCATGAAAAGGGGATCGGT GGTCACGATTGCCTTGCAGGGCAA >CT0999, gi) 21672841 : 948124-948447 ATGAAAAGGGGATCGGTGGTCACGATTGCCTTGCAGGGCAATGACGGGAAGCTACGGCCA GCAGTGGTTG TTCTATCCGATTATTTTCCGGAACATCCCTCCGTAACGGTGTTGCCGATAATCAGTGACT TGCGTTCGAC GCCCTTTTTCCGGATCGATGTCGAGCCAGAGGCACAGAATGGCTTGCTGAAGCCGTCCCG GATCATGATT GACAAAGCTCAGGCGGTGCCGTCGGAAAAGATCGGCAAGGTTATCGGTCTTCTCGACGAT ACCAAAATGA TGGCGGTCAACAGGGCGCTAGCGCTCTGGTTCGGTTTTGCTTGA TGGCGGTCAACAGGGCGCTAGCGCTCTGGTTCGGTTTTGCTTGA 17988344 : 197880-198089, 17988530 >17988530_197330-198730_Brucella_melitensis_chromosome_II . fna_6 [550-759] ATCGAAGCCGAAACTATCCCGCGTGAAGGTCGGAGAACATCGCGCTCGTTTGCGCGCCTA AGGTTTGCGCTCGATCCAGATTTGGGTGCCGGACGTGCTTTCTCCTCATTTCGTGATGAG GCGCACCGTCAGTCGCTTACCGTCGCGTCAAGGAGTCATGCCGCTGATGATTTGGCTTTC ATTAATTCTGTTTCGGACTGGTCTGACGAA >gil17988344 : 198089-198373 ATGAAGCGTGGCGAAATATGGACGGTCGGGGGCGGCAAGGACCGTGCAGGTAAACCGCGT CCAGCTGTGA TTGTGCAGGACGATCGATTTGATGCTACGGGCTCGATAACCATTTGCGCATTCACGACAA ATGAGACCAA TGTGCCTTTATTTCGCCTTGCGGTCGAGCCGAATGAGCGGAATGGCTTGCGGTCGGTGTG CCGCCTTATG GTGGACAAGATCACGACCGCTCCTAAATCCATGATGGCGGTGCAGGTAGGGCGAAATCCT CCAGGTCATA GCTGA GCTGA 23499767 : c1101320-1101529, 23500829 >235008291100330-1101730BrucellasuischromosomeII. fna12 [1199-990] (REVERSE SENSE) ATCGAAGCCGAAACTATCCCGCGTGAAGGTCGGAGAACATCGCGCTCGTTTGCGCGCCTA AGGTTTGCGCTCGATCCAGATTTGGGTGCCGGACGTGCTTTCTCCTCATTTCGTGATGAG GCGCACCGTCAGTCGCTTACCGTCGCGTCAAGGAGTCATGCCGCTGATGATTTGGCTTTC ATTAATTCTGTTTCGGACTGGTCTGACGAA >gil23499767 : c1101320-1101036 ATGAAGCGTGGCGAAATATGGACGGTCGGGGGCGGCAAGGACCGTGCAGGTAAACCGCGT CCAGCTGTGA TTGTGCAGGACGATCGATTTGATGCTACGGGCTCGATAACCATTTGCGCATTCACGACAA ATGAGACCAA TGTGCCTTTATTTCGCCTTGCGGTCGAGCCGAATGAGCGGAATGGCTTGCGGTCGGTGTG CCGCCTTATG GTGGACAAGATCACGACCGCTCCTAAATCCATGATGGCGGTGCAGGTAGGGCGAAATCCT CCAGGTCATA GCTGA GCTGA 30248031 : cl002703-1002936, 30248925 >30248925 1001630-1003100 Nitrosomonas_europaea. fna_11 [1306-1073] (REVERSE SENSE) ATCAAGATGACTATTATTGCAAAAGTAACCTCAAAGGGACAGACCACGATACCGGCTGAT ATTCGTGCAGCGTTGCGTATAAAACCGGGCGATTTGATTATCTGGGAAATGTCGGATGAT GGTAGTGCACGCATTCGACGTGTACAACCGCTCGATATCGAATACTTGAAAGCAGTGGAG GGAACGCTTTCCGAGTGGGCAGGCGCAGCCGATGAGGAAGCTTATCGTGAGTTA >gil30248031 : cl002710-1002360 GTGAGTTATGAACGTTTCACGGTATTGAAAGTGCCTTTTCCGTTTACCGACCGTACGGCT GCCAAAAACC GTCCGGCACTCGTACTCTCGGATGCAGCCACATTCAACGATCCAATCGGCCATTCGGTGC TGGCCATGAT TACCTCAGCCGCCAATCCAGCCTGGCCGCTCGATTGCCTGATCGATGATCTGGTCAGTGC CGGTCTCCCG GCTCCTTCTGTCGTACGCTTCAAGCTGTTCACGCTCGATCACCGGCTGATACGTGGTGAA CTTGGACGAC TTGCCGTCAGTGATAGTATTCAGGTCACACGATCTCTGTATCAGCTTTTCGGAATGGCTG CAGTGCGATA A A >gil15607142 : c755223-754978 ATGCTCAGCTTCCGCGCCGACGACCACGACGTCGACCTGGCCGACGCGTGGGCGCGTCGC CTACACATCG GCCGCTCCGAGCTGCTGCGCGATGCGCTGCGACGTCACTTGGCCGCGCTGGCCGCGGACC AGGATGTCCA GGCCTACACCGAGCGACCGTTGACGGACGACGAGAACGCACTGGCTGAGATCGCCGACTG GGGGCCGGCG GAGGACTGGGCCGACTGGGCCGATGCGGCGCGGTGA >gil15607142 : c754991-754683 ATGCGGCGCGGTGAATTGTGGTTTGCCGCCACACCTGGTGGTGACAGACCAGTACTTGTC CTTACCAGAG

Nucleotide sequences coding for homologs of CcdB toxin-antitoxin pairs

Polypeptide sequences Homologues of vapBC toxin-antitoxin system polypeptides ------------------------------------------------------------ ------------- >gi|15898475|ref|NP_343080. 11 [Sulfolobus solfataricus] MEEVKVTRNYQITIPYEIRQKLGIKIGDKLIVTVDGDKIVIEKKKGNISSLNLTLGKKIT DEEINETINEAGREIADSS >gi|15898476|ref|NP_343081. 1| [Sulfolobus solfataricus] MRLEEKLQTWDTNFIIAIIFRDHEKHEEALKEWEIIEKAYLPLISLSELSYFLIKNGVNL EWNEVISDPKIEIVPNTI EDVRFALANKEKIKGYDDFNDFLILSTAKRLDLPLLTFDKKLKMKS >gi15899784refNP_344389 11 [Sulfolobus solfataricus] MERVKVTRNYQITIPASARSKINIKEGDILEVYLNGDEIVLRKVKTERPRIRLGSKLSLG DIEEAIERGEGNS >gi|15899783|ref|NP_344388. 1| [Sulfolobus solfataricus] MEKAIVDTNVIIYDYVEDSEYHKRAEELLDSLDRWVIPVIWHEIMWFLKGMKLEDKVDDV LAYIRSEKAEWCDCTDNV TDAIGVLNKEKLPLVSYKDMVILSHAIREKLPLATFDRKLSKIAKKYSVSLLQS ------------------------------------------------------------ ------------- >gi|15898765|ref|NP_343370. 1| [Sulfolobus solfataricus] MSLTLRVEVGKKGYIIIPKSVRDLVGIKEGDILILTWGDKIILEPERKVNIREWKKLEEH ERKISYAKRASLGELENI SLEEELKIDFS >gi|15898764|ref|NP_343369. 1| [Sulfolobus solfataricus] MIFLDANFLIYLNSGVSEVKEYYIKLLTYESLFSDPLVIDEVIYVSKKKYGVKYCDTIEF LDEIVLKYLTVLPITIKEYE RAKEIMRKYSVKPSDAFHIAVMLNNSINVILSEDKELDKVAEIKRIWI

------------------------------------------------------------ ------------- >gi|15921382|ref|NP_377051. 1| 84aa long [Sulfolobus tokodaii] MYIAYMKTIMIRDDVYKKLLEIKGDKSFSEIIEELIEESLSVRRKKIEKYFGILNEEEAR GLAKEIEEMRKRTDEDIARK LSNY >gi|15921381|ref|NP_377050. 1| 125aa long [Sulfolobus tokodaii] MKILLESSAIIEYLKGNKKAKEILDKAEDFYVSSLSAYEILLGKINENKILDFLSAFKIL SITLKDSLIASRIYKRLRDK GMLIGSFDILIASQAINRDLTLVTKDTDFLRIKEEYKNLKLFMLS ------------------------------------------------------------ ------------- >gi|15922259|ref|NP_377928. li 73aa long [Sulfolobus tokodaii] MAKTITISEEAYRLLLSEKREGESFSDVIIRLVKSSRKNIMDYAGIWGDMNDEEVNKLFE DLKKMWERWNVNA >gi|15922260|ref, NP_377929. 1} 133aa long virulence-associated protein [Sulfolobus tokodaii] tokodaii] AAEIEVDLENRGEVIGLKDVLISSIALNNNCTIVTGNVKHFERIQGVKVENWK AAEIEVDLENRGEVIGLKDVLISSIALNNNCTIVTGNVKHFERIQGVKVENWK >gi|15921073|ref|NP_376742. 1| 73aa long [Sulfolobus tokodaii] MERVKVTRNYQITIPASIRNKINLKEGDILEVYLNGDEIVLRKVKSERPRIRLGKKLYPE EIEEAIERGEGNN >gi|15921074|ref|NP_376743. 1| 133aa long (Sulfolobus tokodaii] MEKAIIDTNVIIYDYVEDSEYHKKAEELLDSLNKWIIPAIVIHELVWFLKDMKLEDKIND VFAYVRNEKAEVICDSVNNI VDSLEILIREKLPLADYKDMIILSHAIREKLPLVTFDKKLSKIAKKYGVSWS ------------------------------------------------------------ ------------- >gi|15921992|ref|NP_377661. 1| 102aa long protein [Sulfolobus tokodaii] MFLQYSIKTFYFGILSIHMAYTTIKVTDEVKRKLIKLAGEIQAKKGEEISLNDVIELLID FYENKRKIKKGLKMNDFDGL IIEMDTDSSEKVDEWYGKSTS >gi|15921991|ref|NP_377660. 11 144aa long [Sulfolobus tokodaii] MEKVLLDTSYFIAYLNKNDKYHSEALSLSKKIAEFESVITDYILDELLTFLIYRINKNYA INIAKTILNKIDNEELTLYM IGIETLNGALNYLARYDKKLSFTDCTTLSSMDKLRTQFIVSFNSDFDDITLIEFKKPVIN IRYL >gi15920210refNP_375879. 1 84aa long [Sulfolobus tokodaii] MGIQNYLMGYIVTVDERGRVIIPKQIREKLNLKEGSKVEVDLEKDGKIVIKVKRISVDDI YGIAGKEKVEIEEIEEALGF EDND >gi|15920209|ref|NP_375878. 1| 128aa long [Sulfolobus tokodaii] MIDSNVFIYVLFSDPSYGERAKELLKTAEVEDAYSSTLIISQVLSHLERRKKAEVIPMFV NYLQQSGINIVDTRWEDIVN GIKILQELKLSYKLWDDAVILSQMKRLGIDIIYSNDTDFDLLNANRKF GIKIIQELKLSYKLWDDAVILSQMKRLGIDIIYSNDTDFDLLNANRKF >gi15921142refNP-376811. 1| 95aa long [Sulfolobus tokodaii] MFYNFLLYLVIHVNYALDALTRNYQITIPSTIRNRLNIRVGDRLLVYVENNRIIIEKKSG NIASLGLRLGRKFTDEDINK IIAEAGEEIGRDSSS >gi|15921141|ref|NP_376810. 1| 115aa long [Sulfolobus tokodaii] MIAVIFEDHIFHKLAIKDWEKLRKAYLPIIAISELAYFLIMGFSLNDVIDNVLSDPKIEV VENTLEDIYFAIRNSPKSY DDFNDYMIISLARRLKLKISTYDHKMKKKGSRLNG ------------------------------------------------------------ ------------- >gi|15920970|ref|NP_376639. 1| 79aa long [Sulfolobus tokodaii] MRVKVTRNFQITIPAEVREKLNIREGEYVDVTINEKEGIIIVRPYRKKWTTVTLGKRITQ EEIDKAIEEWDDFTKSFT >gi|15920969|ref|NP_376638. 1| 124aa long [Sulfolobus tokodaii] MYSTFEDSERHKEAMKILTENEVVIPQIVVYEYIWVLARLTNNVDLVKQKLEELKDFETA KEDLEDMIKGIEMLKKDNKP IRMLNDYIILAIAKRLNIGLATYDIEDVKAGVRNSVNIYSQHSS TRMLNDYTILAIAKRLNIGLATYDIELVKAGVRNSVNIYSQHSS >gi|18313617|ref|NP_560284. 1| [Pyrobaculum aerophilum] MEVKVTRNYQVTIPAEYRRKLGIKIGDWTVLLEGDRIVIIPAKKRRITFKAGRPVSVEEL ESAVEKALDESTS >gi|18313618|ref|NP_560285. 1| [Pyrobaculum aerophilum] MKVLVDTNVLIYETFEDFERHAEATDIVYTNEVYIPTIVLHEYIWLLLRHFSISYAQAAA KLEQLLSEKNIHVICENLSD LAAGIRMAAEDGAKPSNINDYIILASALNRGLALATYDRELRRAGARRAVTVLPATL ------------------------------------------------------------ ------------- >gi|18313510|ref|NP_560177. 1| conserved within P. aerophilum [Pyrobaculum aerophilum] MLSQSDGKAPSYQHRLIRAPAALQDLYCTKVLLYMSEKEVIKVEVPKWLAERLRKYAAER YGLRRGALSKAIVEILEREL GGPQPSAGGLDRLVGLGLSSPRRWNGEDLAEALRDN >gi] 18313509jref) NP560176. l) [Pyrobaculum aerophilum] MTPELLYKRQKWVEPYRFLEKVKSGNIRGYVLQFAVHGISAILARPDLVEAFLSEIATWR GLEIVKSNMEEEIEAARAAA KVGLDFDDGLHYYYAKKLGVPIVSFDKDFDKTDLKRLEPGEWGG >gi|18311665|ref|NP_558332. 1| protein [Pyrobaculum aerophilum] MEKTTIAVSKKLWQELLSEKERLAAKTMEEAISKILQEYRELKRRIAILEIIEKTGRRAL QQWRSC >gi18311666jref) NP558333. 1 [Pyrobaculum aerophilum] MGASQRALLDTSVLIEILDKGRLSLLPKDPYLSVISIYEYIRYKRDRHFYKERLEEAFSV LGLTNKVIERAAEIFASLKA RGVWSDNDVFIAATAVAYGLPLITKDRYFLKIKTAAGLDWFID

------------------------------------------------------------ ------------- >gi|11499579|ref|NP_070821. 1| [Archaeoglobus fulgidus DSM 4304] MTKTISISDDVYEMLVKIKGKRSFSEVIRELVKKEGNFDLLMVAFGTRSEEEVEKLKREM KEVEEWMQSLCNH >gi|11499578|ref|NP_070820. 1| virulence associated protein C (vapC-1) [Archaeoglobus fulgidus DSM 4304] MKNGCNPCVIIDLFKGDKGLLEKLNGDTVYGISVITLFELQCGSLKEREEIFLEKIPKLN FEESSAKLAGKIFRELKKGA EFQR >gi|11499593|ref|NP_070835. 1| [Archaeoglobus fulgidus DSM 4304] MVRTRTVGKKGQVTIPKEIREKFGLKEGEKWFEIRGDEIILRPEKSGRDYVEELTSIIEK KLEAPEPAELKRLYYGQIE KRVSGL >gi|11499594|ref|NP_070836. 1| [Archaeoglobus fulgidus DSM 4304] MDRLKSAYLDSNVFIYATLYSGKTAEKSKEYLLRASDGEFNAFTSTLTWDEWYWRKVAGI EEGIKAGEILLKMPFIEF L. DVDFAVCEEAQKLAEKYNL. LPRDAIHAVLALKYCDGVIISNDADFDWDGLKRMFD ------------------------------------------------------------ ------------- >gi|11497928|ref|NP_069150. 1| [Archaeoglobus fulgidus DSM 4304] MPKIIEAIYENGVFKPLQKVDLKEGEKAKIVLESISDKTFGILKASETEIKKVLEEIDDF WGVC >gi|11497929|ref|NP_069151. 1| [Archaeoglobus fulgidus DSM 4304] MTSGVFVDTNILVRHLAGDQKAKKLIDQIEIGEIRGYINQIWSEWFVYMRLLTKLDAKTL KRNHEIICKIDLEPVYEI LSIFVELQSSNLITVESRKIMSRYGLLPNDALIAATCKHYGIRKIATFDEDFRRVDFLQW EL ------------------------------------------------------------ ------------- >gil11498682|ref|NP_069910. 11 protein [Archaeoglobus fulgidus DSM 4304] MRIKIEDRKTKRLNFLNSWKPLRLEGRLAAEDIEKLRLLKYENLP >gi|11498681|ref|NP_069909. 1| [Archaeoglobus fulgidus DSM 4304] MRIFLDTNFIVNLIFETEFTETAKAILVKYADSDLITSISVIEETLFVLKRLTRKTNREI AELVANLLDGVEIEVLEKLP LSVFLEVFREYDLLPNDALIAATCKHYDIKKIATFDEDFKRVDFLEVVKL ------------------------------------------------------------ ------------- >gi|11498692|ref|NP_069921. 11 [Archaeoglobus fulgidus DSM 4304] MPKIIEAIYENGVFKPLQKVDLKEGERVRVWSEWAKTRGLLKGCEMEEIIEEIESEGFL >gi|11498691|ref|NP 069920. 1| [Archaeoglobus fulgidus DSM 4304] MRVFFDSNVFLHHLADTKDEATELLERVEDGTFEGIVNDIWSEVIYGYLRATSGLKPYEL RKKILTIDMDLKPVEELFG LFELLPCNFGVGLTKFIKKYKLLPNDALIAATCKHYGINKIATFDEDFRRVEFLEWEL ------------------------------------------------------------ ------------- >gi|11499073|ref|NP_070307. 1| protein [Archaeoglobus fulgidus DSM 4304] MPTKTITITLEAYERLKREKREGESFSDVIIRLTEKRRDLLEFAGKWKDSGEEIEKIILE GRKEFDKHVLS >gi|11499074|ref|NP_070308. 11 [Archaeoglobus fulgidus DSM 4304] MFCLETTFLIDLLRGRDEALKFYAKIRDSKLYTTSISAWELLRGPKLIGKDKEFEVAVEL LESLDVLPFSFNSAKIAVEI EKDLREKGMEVNLIDVLIASVAMEHSLKLVTRDEHFSRIKGLEVERYRPE ------------------------------------------------------------ ------------- >gi|11499771|ref|NP_071014. 1| protein [Archaeoglobus fulgidus DSM 4304] MSIEVKKLDRHGRIVIPKEWRERHGDEVWVVYEDKVEILPRKGNVMRFADSIEVEELKDW EEMRRELYEVR >gi|11499772|ref|NP_071015. 1| [Archaeoglobus fulgidus DSM 43041 MRFVDSNVLIYALLKPKKEPDDRIAEMKGKSVEILRRIQEGEKVATTWHLSEVANVIASR SNEKLSAEFVKEFLTLRNV KVFEVSAEDYLKASLLAVEKGVDVNDALAYVKMREHKIEEIYTFDKHFVKMGVWV ------------------------------------------------------------ ------------- >gi|11499279|ref|NP_070517. 1| [Archaeoglobus fulgidus DSM 4304] MKNIMVRDEVYEKLQKMKKGRESFSDVILRLIEGRKKRGIEILERYAGSLSDSELEKIVM EERRKFRVRSFDS >gi|11499280|ref|NP_070518. 1| virulence associated protein C (vapC-2) [Archaeoglobus fulgidus DSM 4304] MILDTSVIIRIFRDRNFFEVLKERIDDDVKITSVTAYELQRGAVYIMLKHGRDYEFKLIR DFLEEVEILSFTPKDSEISA MIWAKLREKGYELNDADIMISAVSIRENEKLVTLDRDFEYISRVSELDVDILEEEL ------------------------------------------------------------ ------------- >gi|11497686|ref|NP_068907. 1| protein [Archaeoglobus fulgidus DSM 4304] MIPKVIRDKLGIKPDDVLLVDEEGGKIVIEKQDIDDFIEWVKKTRKKVAGEVYRIALEDE FE >gi|11497685|ref|NP_068906. 11 [Archaeoglobus fulgidus DSM 4304] MKIFLDANYLIYLKYSESDEIFDYCVNLLRKIEKYDLVTNMLAIDEVIWILNRKYKIELD EVFEYLDRLLSFLRVVPIEA

EDYDLMKEFMLGYNLKPSDSLHLSSMRRHGVSVIVSEDSDFDRVDWVKRVWIGRGDV ------------------------------------------------------------ ------------- >gi|11497930|ref|NP_069152. 1| [Archaeoglobus fulgidus DSM 4304] MCKPPMRLLTQTGLPRSSERQIRILEIVTGNRKGKHQPKPISKPQPNISMPKIIEAIYEN GVFKPLQKVNFRPGSKVRIV IQEDKKEILRKYKGVFGKAEVEELREYEGEVML >gi|11497931|ref|NP_069153. 1| [Archaeoglobus fulgidus DSM 4304] MIVLDTNIFYNFLFETNLTEKSERILETYEPLFSTFTVWNETIYVTSRKLAEIKFGIKSY VKFRKLVAEEGYSFCAKEIE AFESVIRDLNITVLRDYQNPREISEIMSKFKLLPNDALIAATCRHYGIRKIATFDEDFRR VDFLEWEP >gi|11499936|ref|NP_071181. 1| protein [Archaeoglobus fulgidus DSM 4304] MKVKVTRNFQITIPAEVRRKMGLKLGDVLEVEYNEEKGEAIIRKLGGERRKLKAGRKLTP DEIEALIAEGMGDNL >gi|11499937|ref|NP_071182. 1| [Archaeoglobus fulgidus DSM 4304] MKAVIDTNVIVYDTFEDSVFHQEAMQLLDRIDVWVIPTIVIHEYVWVLKSLKVDVKEIKY KVEEYLNHYKTKMVSENKQI VLSALERIVGGGLSLSRYNDELILAVAGREKISLATFDERLRRQARARGVEVIP >gi|15669165|ref|NP_247970. 1| M. jannaschii predicted coding region MJ0975 [Methano- coccus jannaschii] MVIVMEIWDAIYEKGVLKLKKSINLPEGCEVEIKIIPKKISEKTFGILKLSDKEIKEILE EIENGGE >gi|15669164|ref|NP_247969. 1| [Methanococcus jannaschii] MRRLKMEENKIFFDSNILIYHLCGKVEAKKLIEKVENKEICGFINPIVISEVLFFYIRAT TNKRHYDIKKHPEILKSLDL DIVFELFSIFQILDLNSEIVKISREIIKKYCLLPNDALICSTCKFYKINKICSFDDDFKR VDFLEIIEI ------------------------------------------------------------ ------------- >gi|15669309|ref|NP_248114. 1| [Methanococcus jannaschii] MINMATITIDDDVYKELLKLKGRKSVSEFIKELLEERKRKNLDVFMIAFGSRSEEDVEKL KKELKEAEKWMQSLIQV >gi|15669308|ref|NP_248113. 1| virulence associated protein C (vapC) [Methanococcus jannaschii] MDAVIDTSVIIEIFRGNKDTLYQICDYNCKITSITVFELYCGNLKENEMIMIDSLPKLNF DDKSSKIAGNIFKKLKKEGK IPSVKDLLIASIFY TPSVKDLLIASTFY >gi|20090373|ref|NP_616448. 1| [Methanosarcina acetivorans str. C2A] MPTRTISISEEAYEKLKSLKSSEKDSFSDVILRYYPKKRKLSEVLAEIGPNPELADAIEK VSGEMRAEKMREIDPES >gi|20090374|ref|NP_616449. 1| [Methanosarcina acetivorans str. C2A] MIEMPVLDTSFIVALLRGEPEAHQKLAEMEAEEVPLSTTEINVLELYRGAYLFRKKYQNL EEIKKLLECFQVLELEEPVY EIFASLSARLLSEGKPIGAFDELIAAITLLQEEQIVTRDEHFKRVPGLEVITY ------------------------------------------------------------ ------------- >gi|14520620|ref|NP_126095. 1| protein [Pyrococcus abyssi] MISLSKTITIADDVYYELVKMKGNKSFSELLRELIGKKKKGNLDILMIAFGTMSEEEVKE FKKKIKEVEEWINSWTPVS >gi|14520619|ref|NP_126094. 1| protein [Pyrococcus abyssi] MDKLLDTSVLIEVFRGNAKILTQLPPEEEYAIPSIVLFELLCGGLKPKQRLALEKMPWNF DKTSAEVAGEIFKDLISKG LRPPTKDLLIAATAIAHNIPLYTCDRGFERFKEYGLKLVILER LRPPTKDLLIAATAIAHNIPLYTCDRGFERFKEYGLKLVILER >gi|14520978|ref|NP_126453. 1| protein [Pyrococcus abyssi] MPITKVTRNYQVTLPAEVRKVLGIREGDFLEVEVRGDEIVMRKLRKNRRTLKLGRNLTPE DIERTIEEGMRECMQ >gi|14520979|ref|NP_126454. 1| protein [Pyrococcus abyssi] MHAVIDTDILIYDTFEDLEFHEEARALLDSLSKWYVPTIVLQEYIWFFKRNNFSLLDAKS MLMEYVRDPRFKGLGESHEV IIHALKILEENELSLSHFNDAIILYQAFSRKYPLATFDEKLRKLATKHGIRVLPEl ------------------------------------------------------------ ------------- >gi|14520335|ref|NP_125810. 1| protein [Pyrococcus abyssi] MGITKVTRNYQITIPSDVRKKLGIKVGDVLIIEIEDGKAVIKKSDLELPLLPGGRGLKVE DIEDAIRRGQREEG >gi|14520334|ref|NP_125809. 1| protein [Pyrococcus abyssi] MTVIDTNVFIYAILRDSEFNSRARNLLASLERWIVPSIVLYELYWFFREEGYGRDEITNV ISSILNSPRTRVIGDNGRYT KRALELTKNPRRFNDMIILATAEQFKRLATYDKRLKKEAERLGIETMP ------------------------------------------------------------ ------------- >gi|14521382|ref|NP_126858. 1| protein [Pyrococcus abyssi] MENAYELFQKLPDDLKREVIDYIEFLLEKKAKKKRGQLKLTWKGALKELRDKYSSVELQH KALEWWE >gi|14521383|ref|NP_126859. 1| protein [Pyrococcus abyssi]

MYLVDTNVFLEIFLNQEKANEAEEFLTKTPTEYSHISDFSLYSIGIILSRQKKYAVFSDF VEDVLLEGGVTLLRLSPFDL GSVINAAERFNLDFDDAYQYTLARKYNLKIVSFDSDFDKTDIGRLLPAQALRR ------------------------ 7------------------------------------------------ >gi|18977594|ref|NP_578951. 1l protein [pyrococcus furiosus DSM 3638] MFLSVHPNSITLKYDACIQCIMVSIMVKTITISDDVYNELLRIKGNKSFSEVLRELLKER KGNKEVLKRIFGILSEEEYQ EVKKRLKELEGEFEKWEQSLTQM >gi|18977595|ref|NP_578952. 1| protein [Pyrococcus furiosus DSM 3638] MGAVLDTNVIIEIARGNRRILEKVLSTDSTFYITSITKFEIFLGFPKKEELIWLNSLEEL PFDGKSAEIAAYLYKKLREK GIMLGIRDLFIGSIALVNDLPIJITLDKDFLHLKEFGLEVEILR GIMLGIRDLFIGSIALVNDLPIITLDKDFLHLKEFGLEVEILR >gi|18976945|ref|NP_578302. 1| protein [Pyrococcus furiosus DSM 3638] MPITKVTRNYQITIPAEIRKALGIKEGELLEVRLENGKIIIERLKKERKTLKLGKKLTLE EIEKAIEEGMKQCMQ >gi|18976946|ref, NP_578303. 1| protein [Pyrococcus furiosus DSM 3638] MHAVIDTNVLIYDTFSDSEFHKESRSLLNSLDRWYIPSIVLQEYVWFFRSQGFSSREAKI MLSEYISDPRFRGLVEDHNV ILRAIDILERENLSLSRFNDMIILVHAIEKGTLATFDQKLRKLARKLSVEILP ------------------------------------------------------------ ------------- >gi|18977185|ref|NP_578542. 1| protein [Pyrococcus furiosus DSM 3638] MGMEVKRIDSQGRIVLPKEWRKRWGNEVILIEFEDRIEILPKRKPKLSEFFDIIEVEEVE EDVEKELLKELAGEYE >gi|18977184|ref|NP_578541. 11 protein [Pyrococcus furiosus DSM 3638] MRFIDSNVFLYAMIKPKGNTSKEILKKKEKAKKILLRVENGEDWTTLIHLSEIANILEAK VNLTTAVRFLENLLLAENV KILPVSVEEYLKAVLISKEKGISVNDALAYLKMKELNIKEIYTFDRHFQNLDVEVIQD ------------------------------------------------------------ ------------- >gi|18977579|refìNP_578936. 1| protein [Pyrococcus furiosus DSM 3638] MKTIAVDEETWEAIKKLKARLDAKSYDEVLKKLIQAWHTLELETKAESISLEDDEAELVL SVIRDRSKLVEEGSRK >gi|18977578|ref|NP_578935. 1| protein [Pyrococcus furiosus DSM 3638] MNPMPRKISFDPPSFIQLTRKQNKELLEFVLAEFEIYLPITTVHAYLLAKAFKGKNPKEE VQKLRDIVKIVDLTDELLGE IAEIDASLIKDGYFFTLEDLITAVSAITSKSLLVWGNAEKYSPLRKYGLDCVNYEKFLEE VEVLAREEAKREKII k >gi|18977210|ref|NP_578567. 1| protein [Pyrococcus furiosus DSM 3638] MKLTHKFKSFLNQILFGENMQEIEKVLSKLPPELKKEVFDYAEFLLKKYREKKRKGFTFS WEGKVKSELSSVELQHKALE WRT >gi|18977211|ref|NP_578568. 1| protein [Pyrococcus furiosus DSM 3638] MFLVDTNVFLEILLGQKKKEEAKKFLSENIDRLYMTDFSLHSIGVILFKLRKPEVFEEFI EDVLPNVEILSLPVEGYPEL IRIHKTLNLDFDDAYQCAVANVFDLTWTMDTDFTKALNYVKILFL >gi1189769481refINP_578305. 11 protein [Pyrococcus furiosus DSM 3638] MQIVEAIYEDGVLKLLKNLKLKEHSKVIIKVIDEEEIEKILDSRDY >gi|18976947|ref|NP_578304. 1| protein [Pyrococcus furiosus DSM 3638] MNPSEVFLDSSILVGLNLGDENAKALVKSLIERGFTLVINPWFSETAYKVMFTLALRDEL KGFITSKSIWIDMLGFMER SKESIEQLQILRNSEIATFDEDFKKVDFHRSY SKESIEQLQILRNSEIATFDEDFKKVDFHRSY >gi|15607441|ref|NP_214814. 1| protein Rv0300 [Mycobacterium tuberculosis H37Rv] MSDVLIRDIPDDVLASLDAIAARLGLSRTEYIRRRLAQDAQTARVTVTAADLRRLRGAVA GLGDPELMRQAWR >gi|15607442|ref|NP_214815. 1| protein Rev0301 [Mycobacterium tuberculosis H37Rv] MTDQRWLIDKSALVRLTDSPDMEIWSNRIERGLVHITGVTRLEVGFSAECGEIARREFRE PPLSAMPVEYLTPRIEDRAL EVQTLLADRGHHRGPSIPDLLIAATAELSGLTVLHVDKDFDAIAALTGQKTERLTHRPPS A >gi) l5607736refNP215110. 1 protein Rv0596c [Mycobacterium tuberculosis H37Rv] MSATIPARDLRNHTAEVLRRVAAGEEIEVLKDNRPVARIVPLKRRRQWLPAAEVIGELVR LGPDTTNLGEELRETLTQTT DDVRW >gi|15607735|ref|NP_215109. 11 protein Rv0595c [Mycobacterium tuberculosis H37Rv] MNVRRALADTSVFIGTEATRFDPDRFAGYEWGVSWTLGELRLGVLQASGPEAAARRLSTY QLAQRFEPLGIDEAVSEAW ALLVSKLRAAKLRVPINDSWIAATAVAHGIAILTQDNDYAAMPDVEVITI >gij15607766) refJNP215140. 1) protein Rv0626 [Mycobacterium tuberculosis H37Rv] MSEVASRELRNDTAGVLRRVRAGEDVTITVSGRPVAVLTPVRPRRRRWLSKTEFLSRLRG AQADPGLRNDLAVLAGDTTE DLGPIR >gi|15607767|ref|NP_215141. 1, protein Rv0627 [Mycobacterium tuberculosis H37Rv] MSTTPAAGVLDTSVFIATESGRQLDEALIPDRVATTWTLAELRVGVLAAATTDIRAQRLA TLESVADMETLPVDDDAAR MWARLRIHLAESGRRVRINDLWIAAVAASRALPVITQDDDFAALDGAASVEIIRV ------------------------------------------------------------ ------------- >gi|15607802|ref|NP_215176. 1, protein Rv0662c [Mycobacterium tuberculosis H37Rv] MFLPNTRAYRRYNRSVWAVRGSTRPQWQPPPKFQHAKCMSMRLAHRLQILLDDECHRRIT AVARERGVPVATWREAIDR GLVSPAGRRKSAGRRLLDAADMSVPEPRELKQELEALRARRG >gi|15607801|ref|NP_215175. 1| protein Rv0661c [Mycobacterium tuberculosis H37Rv]

MIVLDTTVLVYAKGAEHPLRDPCRDLVAAIADERIAATTTAEVIQEFVHVRARRRDRSDA AALGRVTMPNCSRRYSPSIE ATSKRGLTLFETTPGLEACDAVLAAVAASAGATALVSADPAFADLSDWHVIPDAAGMVSL LGDR ------------------------------------------------------------ ------------- >gi|15607804|ref|NP 215178. 1| protein Rv0664 [Mycobacterium tuberculosis H37Rv] MEKSRCHAVAHGGGCAGSAKSHKSGGRCGQGRGAGDSHGTRGAGRRYRAASAPHPLAVGA HLRDELAKRSADPRLTDELN DLAGHTLDDL >gi|15607805|ref|NP_215179. 11 protein Rv0665 [Mycobacterium tuberculosis H37Rv] MTEGEVGVGLLDTSVFIARESGGAIADLPERVALSVMTIGELQLGLLNAGDSATRSRRAD TLALARTADQIPVSEAVMIS LARLvADcRAAGvRRsvKLTDALIAATAEIKv LARLVADCRAAGVRRSVKLTDALIAATAEIKV >giìl5608536ìref|NP_215914. 1| protein Rv1398c [Mycobacterium tuberculosis H37Rv] MKRTNIYLDEEQTASLDKLAAQEGVSRAELIRLLLNRALTTAGDDLASDLQAINDSFGTL RHLDPPVRRSGGREQHLAQV WRATS >gi|15608535ìref|NP_215913. 1| protein Rv1397c [Mycobacterium tuberculosis H37Rv] MILVDSDVLIAHLRGWAARDWLVSARKDGPLAISWSTAELIGGMRTAERREVWRLLASFR VQPATEVIARRAGDMMRR YRRSHNRIGLGDYLIAATADVQDLQLATLNVWHFPMFEQLKPPFAVPGHRPRA ------------------------------------------------------------ ------------- >gi|15608976|ref|NP_216355. 1| protein Rv1839c [Mycobacterium tuberculosis H37Rv] MSKRLQVLLDPDEWEELREIARRHRTTVSEWVRRTLREAREREPRGDLDMKLRSVRAAAR HEFPTADVEQMLEEIERGRG AEREGSR >gi|15608975|ref|NP 216354. 1ì protein Rv1838c [Mycobacterium tuberculosis H37Rv] MILVDSNIPMYLVGASHPHKLDAQRLLESALSGGERLVTDAEVLQEICHRYVAIKRREAI QPAFDAIIGWDEVLPIERT DVEHARDALLRYQTLSARDALHIAVMAHHDITRLMSFDRGFDSYPGIKRLA ------------------------------------------------------------ ------------- >giìl5609089|refìNP 216468. 1| protein Rv1952 [Mycobacterium tuberculosis H37Rv] MIRNLPEGTKAALRVRAARHHHSVEAEARAILTAGLLGEEVPMPVLLAADSGHDIDFEPE RLGLIARTPQL >gi|15609090|refìNP 216469. 1| protein Rv1953 [Mycobacterium tuberculosis H37Rv] MTYVLDTNWSALRVPGRHPAVAAWADSVQVAEQFWAITLAEIERGVIAKERTDPTQSEHL RRWFDDKVLRIFVFARRG TNLIMQPLAGHIGYSLYSGISWF TNLIMQPLAGHIGYSLYSGISWF >gi|15609663|ref|NP_217042. 1| protein Rv2526 [Mycobacterium tuberculosis H37Rv] MTVKRTTIELDEDLVRAAQAVTGETLRATVERALQQLVAAAAEQAAARRRRIVDHLAHAG THVDADVLLSEQAWR >gi|15609664|ref|NP 217043. 1| protein Rv2527 [Mycobacterium tuberculosis H37Rv] MTTWILDKSAHVRLVAGATPPAGIDLTDLAICDIGELEWLYSARSATDYDSQQTSLRAYQ ILRAPSDIFDRVRHLQRDLA HHRGMWHRTPLPDLFIAETALHHRAGVLHHDRDYKRIAWRPGFQACELSRGR ------------------------------------------------------------ ------------- >gi|15609684|ref|NP_217063. 1| protein Rv2547 [Mycobacterium tuberculosis H37Rv] MRTQVTLGKEELELLDRAAKASGASRSELIRRAIHRAYGTGSKQERLAALDHSRGSWRGR DFTGTEYVDAIRGDLNERLA RLGLA >gi|15609685|ref|NP_217064. 1| protein Rv2548 [Mycobacterium tuberculosis H37Rv] MKLIDTTIAVDHLRGEPAAAVLLAELINNGEEIAASELVRFELLAGVRESELAALEAFFS AWWTLVTEDIARIGGRLAR RYRSSHRGIDDVDYLIAATAIWDADLLTTNVRHFPMFPDLQPPY ------------------------------------------------------------ ------------- >gi|15609895|ref|NP_217274. 1ì protein Rv2758c [Mycobacterium tuberculosis H37Rv] MHRGYALWCSPGVTRTMIDIDDDLLARAAKELGTTTKKDTVHAALRAALRASAARSLMNR MAENATGTQDEALVNAMWR DGHPENTA >gi|15609894|ref|NP_217273. 1ì protein Rv2757c [Mycobacterium tuberculosis H37Rv] MTTRYLLDKSAAYRAHLPAVRHRLEPLMERGLLARCGITDLEFGVSARSREDHRTLGTYR RDALEYVNTPDTVWVRAWEI QFALTDKGFHRSVKIPDLIIAAVAEHHGIPVMHYDQDFERIAAITRQPVEWVVAPGTA ------------------------------------------------------------ ------------- >gi|15609146|ref|NP_216525. 1| protein Rv2009 [Mycobacterium tuberculosis H37Rv] MYSGWSRTNIEIDDELVAAAQRMYRLDSKRSAVDLALRRLVGEPLGRDEALALQGSGFDF SNDEIESFSDTDRKLADES >gi|15609147|ref|NP_216526. 1| protein Rv2010 [Mycobacterium tuberculosis H37Rv] MIVDTSVWIAYLSTSESLASRWLADRIAADSTVIVPEWMMELLIGKTDEDTAALRRRLLQ RFAIEPLAPVRDAEDAAAI HRRCRRGGDTVRSLIDCQVAAMALRIGVAVAHRDRDYEAIRTHCGLRTEPLF >gil5608698refNP216076. lj protein Rvl560 [Mycobacterium tuberculosis H37Rv] MYRWCMSRTNIDIDDELAAEVMRRFGLTTKRAAVDLALRRLVGSPLSREFLLGLEGVGWE GDLDDLRSDRPD >giìl5608699|ref|NP_216077. 1| protein Rv1561 [Mycobacterium tuberculosis H37Rv] MILIDTSAWVEYFRATGSIAAVEVRRLLSEEAARIAMCEPIAMEILSGALDDNTHTTLER LVNGLPSLNVDDAIDFRAAA GIYRAARRAGETVRSINDCLIAALAIRHGARIVHRDADFDVIARITNLQAASFR ------------------------------------------------------------ ------------- >gi|15840067|ref|NP_335104. 1| protein [Mycobacterium tuberculosis CDC1551] MEVGVRDLRNRTSQWDAVKAGVPVTLTVHGEPVADIVPHRRRIRWLSGRICAMSSPSARP TRASPMNSTTWPVIPSTTC DRGRGRGRPARYVGLHCARERRCNRGPA >gi|15840068|refìNP_335105. 1 protein [Mycobacterium tuberculosis CDC1551] MTEGEVGVGLLDTSVFIARESGGAIADLPERVALSVMTIGELQLGLLNAGDSATRSRRAD TLALARTADQIPVSEAVMIS LARLVADCRAAGVRRSVKLTDALIAATAEIKV LARLVADCRAAGVRRSVKLTDALIAATAEIKV >gi|15839999|ref|NP_335036. 11 protein [Mycobacterium tuberculosis CDC1551] MSATIPARDLRNHTAEVLRRVAAGEEIEVLKDNRPVARIVPLKRRRQWLPAAEVIGELVR LGPDTTNLGEELRETLTQTT DDVRW >gi|15839998|ref|NP 335035. 1| [Mycobacterium tuberculosis CDC1551] MVNVRRALADTSVFIGIEATRFDPDRFAGYEWGVSWTLGELRLGVLQASGPEAAARRLST YQLAQRFEPLGIDEAVSEA

WALLVSKLRAAKLRVPINDSWIAATAVAHGIAILTQDNDyAAMpDvEVITI WALLVSKLRAAKLRVPINDSWIAATAVAHGIAILTQDNDYAAMPDVEVITI >giìl5840065ìref|NP_335102. 1| DNA-binding protein, CopG family [Mycobacterium tuber- culosis CDC1551] MAAALFLPNTRAYRRYNRSVWAVRGSTRPQWQPPPKFQHAKCMSMRLAHRLQILLDDECH RRITAVARERGVPVATVVRE AIDRGLVSPAGRRKSAGRRLLDAADMSVPEPRELKQELEALRARRG >gi|15840064|refìNP_335101. 1| protein [Mycobacterium tuberculosis CDC1551] MIVLDTTVLVYAKGAEHPLRDPCRDLVAAIADERIAATTTAEVIQEFVHVRARRRDRSDA AALGRVTMPNCSRRYSPSIE ATSKRGLTLFETTPGLEACDAVLAAVAASAGATALVSADPAFADLSDWHVIPDAAGMVSL LGDR ------------------------------------------------------------ ------------- >gi1158408561refINP_335893. 11 transcriptional regulator, CopG family [Mycobacterium tuberculosis CDC1551] MIWCMKRTNIYLDEEQTASLDKLAAQEGVSRAELIRLLLNRALTTAGDDLASDLQAINDS FGTLRHLDPPVRRSGGREQH LAQVWRATS >gi|15840855|ref, NP_335892. 1| [Mycobacterium tuberculosis CDC1551] MILVDSDVLIAHLRGWAARDWLVSARKDGPLAISWSTAELIGGMRTAERREVWRLLASFR VQPATEVIARRAGDMMRR YRRSHNRIGLGDYLIAATADVQDLQLATLNVWHFPMFEQLKPPFAVPGHRPRA ------------------------------------------------------------ ------------- >gi|15841307ìref|NP_336344. 11 DNA-binding protein, CopG family [Mycobacterium tuber- culosis CDC1551] MSKRLQVLLDPDEWEELREIARRHRTTVSEWVRRTLREAREREPRGDLDMKLRSVRAAAR HEFPTADVEQMLEEIERGRG AEREGSR >gi|15841306|refìNP_336343. 11 [Mycobacterium tuberculosis CDC1551] MILVDSNIPMYLVGASHPHKLDAQRLLESALSGGERLVTDAEVLQEICHRYVAIKRREAI QPAFDAIIGWDEVLPIERT DVEHARDALLRYQTLSARDALHIAVMAHHDITRLMSFDRGFDSYPGIKRLA ------------------------------------------------------------ ------------- >gill58414231refiNP-336460. 11 protein [Mycobacterium tuberculosis CDC1551] MEQIVIRNLPEGTKAALRVRAARHHHSVEAEARAILTAGLLGEEVPMPVLLAADSGHDID FEPERLGLIARTPQL >giìl5841424|ref|NP_336461. 1| [Mycobacterium tuberculosis CDC1551] MTYVLDTNWSALRVPGRHPAVAAWADSVQVAEQFWAITLAEIERGVIAKERTDPTQSEHL RRWFDDKVLRIFVFARRG TNLIMQPLAGHIGYSLYSGISWF TNLIMQPLAGHIGYSLYSGISWF >gi|15842060|ref|NP_337097. 11 protein [Mycobacterium tuberculosis CDC1551] MTVKRTTIELDEDLVRAAQAVTGETLRATVERALQQLVAAAAEQAAARRRRIVDHLAHAG THVDADVLLSEQAWR >gi|15842061|ref|NP_337098. 1| protein [Mycobacterium tuberculosis CDC1551] MTTWILDKSAHVRLVAGATPPAGIDLTDLAICDIGELEWLYSARSATDYDSQQTSLRAYQ ILRAPSDIFDRVRHLQRDLA HHRGMWHRTPLPDLFIAETALHHRAGVLHHDRDYKRIAWRPGFQACELSRGR ------------------------------------------------------------ ------------- >gi|15842083ìref|NP_337120. 1| DNA-binding protein, CopG family [Mycobacterium tuber- culosis CDC1551] MYGDVMRTQVTLGKEELELLDRAAKASGASRSELIRRAIHRAYGTGSKQERLAALDHSRG SWRGRDFTGTEYVDAIRGDL NERLARLGLA >gi|15842084, refìNP_337121. 1| protein [Mycobacterium tuberculosis CDC1551] MKLIDTTIAVDHLRGEPAAAVLLAELINNGEEIAASELVRFELLAGVRESELAALEAFFS AWWTLVTEDIARIGGRLAR RYRSSHRGIDDVDYLIAATAIWDADLLTTNVRHFPMFPDLQPPY RYRSSHRGIDDVDYLIAATAIWDADLLTTNVRHFPMFPDLQPPY >gi|15842296ìrefìNP_337333. 1| protein [Mycobacterium tuberculosis CDC1551] MHRGYALWCSPGVTRTMIDIDDDLLARAAKELGTTTKKDTVHAALRAALRASAARSLMNR MAENATGTQDEALVNAMWR DGHPENTA >giì15842295|ref|NP_337332. 1| protein [Mycobacterium tuberculosis CDC1551] MTTRYLLDKSAAYRAHLPAVRHRLEPLMERGLLARCGITDLEFGVSARSREDHRTLGTYR RDALEYVNTPDTVWVRAWEI QEALTDKGFHRSVKIPDLIIAAVAEHHGIPVMHYDQDFERIAAITRQPVEWWAPGTA >gi|15842405|ref|NP_337442. 1| protein [Mycobacterium tuberculosis CDC1551] MSLSNWLRQAGLRQLEAQRQRPLRTAQELREFFASRPDETGAEPDWQAHLQVMAESRRRG LPAP >gi|15842406|ref|NP_337443. 11 protein [Mycobacterium tuberculosis CDC1551] MIFVDTNVFMYAVGRDHPLRMPAREFLEHSLEHQDRLVTSAEAMQELLNAYVPVGRNSTL DSALTLVRALTEIWPVEAAD VAHARTLHHRHPGLGARDLLHLACCQRRGVTRIKTFDHTLASAFRS VAHARTLHHRHPGLGARDLLHLACCQRRGVTRIICTFDHTLASAFRS >gi|15841491|ref|NP_336528. 11 protein [Mycobacterium tuberculosis CDC1551]

MYSGWSRTNIEIDDELVAAAQRMYRLDSKRSAVDLALRRLVGEPLGRDEALALQGSGFDF SNDEIESFSDTDRKLADES >gi|15841492|ref|NP_336529. 11 protein [Mycobacterium tuberculosis CDC1551] MIVDTSVWIAYLSTSESLASRWLADRIAADSTVIVPEWMMELLIGKTDEDTAALRRRLLQ RFAIEPLAPVRDAEDAAAI HRRCRRGGDTVRSLIDCQVAAMALRIGVAVAHRDRDYEAIRTHCGLRTEPLF >gi|15841027|ref|NP_336064. 1| protein [Mycobacterium tuberculosis CDC1551] MYRWCMSRTNIDIDDELAAEVMRRFGLTTKRAAVDLALRRLVGSPLSREFLLGLEGVGWE GDLDDLRSDRPD >gi|15841028|ref|NP_336065. 1| protein [Mycobacterium tuberculosis CDC1551] MILIDTSAWVEYFRATGSIAAVEVRRLLSEEAARIAMCEPIAMEILSGALDDNTHTTLER LVNGLPSLNVDDAIDFRAAA GIYRAARRAGETVRSINDCLIAALAIRHGARIVHRDADFDVIARITNLQAASFR ------------------------------------------------------------ ------------- >giì29832236|ref|NP_826870. 1| protein [Streptomyces avermitilis MA-4680] MSVTQIDLDDEALAEAMRLMGVTTKKETVNAALRDYVARIKRLDAAEKLAARGARGEFEQ AAAAYYAGKRARREAFE >gi|29832237|ref|NP_826871. 1ì protein [Streptomyces avermitilis MA-4680] MITYLLDTSALWHLFRTPGALAPWEGHIAAGVFHLCEPTRAEFLYSATSPTHRDELAEEL DALCLLSPVPKNAWRWVDTA QYKLTQQGQHRAAGAIDLLVCATAVHHGHTVLHVDNDFATVAGVLKELQQRDVRA ------------------------------------------------------------ ------------- >gi|17227999|ref|NP_484547. 1| unknown protein [Nostoc sp. PCC 7120] MNTRIQFTAKVEQGKIIIPDEYISMVGDNLIEVIIKPKPSRLMDRLAENPLTAVGWRDLS RDDIHE >giìl7228000ìref|NP_484548. 1| unknown protein [Nostoc sp. PCC 7120] MIFMNNFIDKKFIDSNIWLYRFLHDPKVDPQVQQLKRSMAINLTQAVDRSIWSTQVITET CAVLKRKTGISEQNILELV EEFEEQCEIVNLTTSEIKEACRLRDKYSFSYWDSLVIATALKSQAKVLYSEDMQNGLLIE NQLTIINPFVGSGNR ------------------------------------------------------------ ------------->giìl7231113|ref|NP 487661. 1| unknown protein [Nostoc sp. PCC 7120] MQMEWEFQGIVKDGVIQIPEIYKGELDGESVKVIVMKKVRKTAAVDIIAELIEHPVEFEW PPLNREEIYDRNS >gi|17231114ìref|NP_487662. 1| unknown protein [Nostoc sp. PCC 7120] MTAIHENGYFLDSNIWIYALANNQDINKRNIACRLIDAEGVIISTQVINEVCLNLIKKSS FTEQQITQLIEAFYKGSHII SFNRDILVNSSNLRSRYKLSFWDSLIVACALAAGASILYSEDMQDGLWDSQLQIVNPFK >gi|17229689|ref|NP_486237. 1ì unknown protein [Nostoc sp. PCC 7120] MLTSHSHSMQIILNLDESLLNEASQLTNLASQEELVNFALQELVRSRRKKNLLDLAGQIQ FAPDFDHKALRETRHAAD >gil7229688Jref) NP486236. l) protein [Nostoc sp. PCC 7120] MLLIDTSVWIGVFRDRSDQVRQQLETLIAEREVLLTRFTQLELLQGSLNEQEWTLLSTYL ETQNYVELTVQSWQAAARIY FDLRRQGLIVRSPIDCCIAQVALENNLLLIHNDRDFETIAQVRALQHLRFQP ------------------------------------------------------------ ------------- >gi|17228989ìref|NP_485537. 1| unknown protein [Nostoc sp. PCC 7120] MTSREQLIQELAEVPDELVKVMLDFLHRLQTTRSHHPLAKFAGILSDNEAADLQEAIQAD CRQVDLNEW >gi|17228988|ref|NP_485536. 1| virulence associated protein C [Nostoc sp. PCC 7120] MSGEIALDTSVAIRFLNGDPDWSRVLALPEIFLSWWGELLFGAENSTRPLKNLPRYLEFM EVCTWPVEKRTAVIYA QTRSALKRKGRPIPMNDVWIAAHCLEHGWVLVTDNSDFDYVDGLVIEHW >gi|17230970|refìNP_487518. 1ì unknown protein [Nostoc sp. PCC 7120] MTSIKAKLIEAIETVPDSILEQTLDYLEYLKTKEQKPQTLSQEIPQKEGEPILRGSKAKD LLKFAKTWQGDDFEECLQLV YDTRSQAEF >gi|17230971ìref|NP_487519. 1| similar to nitrogen regulation protein NtrR [Nostoc sp. PCC 7120] MYLLDTNHCSRIIFGDSNLIQQLQLNSEAGIATSVWCGELLYMAAKSDRSVANLQQVRVF LDTIDIYPVNFSISEVYGN LKGKLVNAFGPKEKAQRRNFNLQALGFGDNDLWIAATAIHYNLTWSTDNDFRRIQQVETL LLESWLAS >gi|16329605|ref|ÑP_440333. 11 virulence associated protein B [Synechocystis sp. PCC 6803] MNTAQISTDGTHQIVILPENFTIAGSEVYIKKIGSTIILIAKNNPWQSLIESLDQFSDDF MKTREQPPLDIREEF >gi|16329604ìref|NP_440332. 1ì virulence associated protein C [Synechocystis sp. PCC 6803] MKYLLDTNICIYLIKKKPFKVLAKFQTLEISDIGISSITVAELEYGVSKSQQQSKNRDAL MQFLMPLEIVEFNSGSGDRL WQH >gi|16331533|ref|ÑP_442261. 11 PEMI-like protein homologue [Synechocystis sp. PCC 6803] MKRSVTMSSTYWKLDSRGKSQSLTLPEDLRLNATEVEIYCQDGRLIIEPLPQPSLLAKLV LLDDIEESFPENFTDNLPL

DNINL >gill63315321refINP-442260. 11 virulence associated protein C [Synechocystis sp. PCC 6803] 6803] YGKIRAILEHQGTPIGGNALLIASQAIYANLILVTDNTGEFKRMPGLSVENWL YGKIRAILEHQGTPIGGNAI, LIASQA=YANLILVTDNTGEFKRMPGLSVENWL >gi|20808932|refìNP_624103. 1| protein [Thermoanaerobacter tengcongensis] MKKSKRKMEIQNITLSLPKDLLQKIKHIAIDRQTSVSGLLTETLEEIVRKEDLYERAKLR HISILEKGFDLGTEGKITWS RDDLYERQ >gi|20808933|ref|NP_624104. 11 [Thermoanaerobacter tengcongensis] MIYMKGNKDLQFVDTNVLVYAYDVSAGEKHEIAKELLKELWYERNGCLSTQVLQEFYVTI TKKVKKPLSPVEAAEIISDL RSWKLSVIDIKDILEAIRVSQRYMISFWDSLIIVSAVNLDCEIIWSEDLNSGQYFGKVRV QNPFNK >gi16124288refNP_418852. 1 vapB family protein [Caulobacter crescentus CB15] MARATGKTFRSGNSEAVRLPRDLAFGADVELTLIRSGDVLTIYPSKGSIADLVATLNQMP RPDSVEIRDEDLFPERPGL >gi|16124287|refìNP_418851. 1| vapC protein [Caulobacter crescentus CB15] MAYVLDTNVAIHLRDGDPEVTTRVTALNGAILLSIISRVELEGGVYREAAQAGLRRSRLD VMLKVLPVLDFDGAAADEYR RIVESAGYSRRKWDRMIAAQALAHRATFVTFNADDFRDIPGLSLLAW RIVESAGYSRRKWDRMIAAQALAHRATFVTFNADDFRDIPGLSLLAW >gi|17934913lref|NP_531703. 11 [Agrobacterium tumefaciens str. C58 (U. Washington)] MRTNIELDDALIAEAMEITGLPTKKATVEKALRDLVENLGRRKALQELRGIGWKGDLEEV RGSWSADSIKSQDAAE >gi|17934912ìref|NP_531702. 1| [Agrobacterium tumefaciens str. C58 (U. Washington)] MIWDTSVWIDWFQNKQTPQVATLSDINDLSDVIIGDIILLEILQGERNERRAAAIESRLK VFELVSMLTPEFAVAAAAN YRKLRGLGKTVRKTADLIIGTYCIEHGHKLLQNDRDFQPMADHLGLQFV >gi|27377546|ref|ÑP_769075. 11 bsl2435 [Bradyrhizobium japonicum] MADHNTAPDTLPADDTWTLANAKARLSQVIDRAQTGPQIITRHGKPNAVIVSAEEWARKT ARKGTLAEFLLASPLRGADL ALERMHDAPRDEMP >gi|27377545|ref|NP_769074. 1| plasmid stability protein [Bradyrhizobium japonicum] MNLLLDTNVLSEVQRPAPSPKVLAWLDTIDEDRAFISVASIAELRRGIALLEDGRRRSAL AAWLAHDLPARFADRVLPID HAVAEHWGDLMAQSRRSGVTLSVMDGFFAATALAHSLSLVTRNVKDFAAFGVPLLNPWDD P ------------------------------------------------------------ ------------- >gi|13474236ìrefìNP_105804. 1| unknown protein [Mesorhizobium loti] MMAGTHRSMSLGREFDMAEPQLSVRSAKARDLAHRLARRENRSIADWERALESYEIREAG REPASTFYASLTASSGVDI DLEKVIREGRELHSGIEH >gi|13474235|ref|NP_105803. 1| plasmid stabilization protein [Mesorhizobium loti] MIFVDTNVISESLKKTPDPAVLAWLVRNDAELALPTVTIAEIAFGIQKIRPDERADRLEQ GLSRWRHRFADRIFGLTEEA ALAYGAIMGAATRQGPGMSAPDGMIAAIARVNGGRLATRNLNDFGTTSLDLISPWNF ------------------------------------------------------------ ------------- >gi|13474916|refìNP_106486. 1| unknown protein [Mesorhizobium loti] MSSSQKRAIQNYRSRLSERGLARFEVLGRDADRDLIRSLARRLAEDGPDASSLRAAVSQT IAGEPPKLVGILAALRRSPL VGADLDLSSPHEEGRKIDL >gi|13474917ìref|NP_106487. 1ì plasmid stabilization protein [Mesorhizobium loti] MTRYLLDTNIISDWVKSQPSESLLAWMSRQRDEDLFIASLTVAEILRRVLEKPRGKKRDA LDNWFSGPEGPQALFAGRIL SFDDKAGLIWARLMAGGKLAGKPRSGLEGKMAETQIEWSAPNPAGRAPR >gi|13471641|ref|NP_103207. 1| NtrP protein [Mesorhizobium loti] MPQHRHTTTPPPKEAKLFRNNRSQAVRIPVEFELPGDKVLISREGDRLVIEPLRKPGLAA LLAQWAKEAPLGPEDNFPEI NDAPVEAEDIF >gi|13471640|ref|NP_103206. 1| NtrR protein [Mesorhizobium loti] MRFMLDTNIISDMIRNPAGKAAGAMVREGDAAVCTSIWASELRYGCARKGSTKLLKKVED LLAEIPVLPLDVPVDAEYG ALRAELEAVGQPIGYNDLFIAAHACVLGTTLVTANIGEFTRIRKLKVENWLE ------------------------------------------------------------ ------------- >gi|15965038|ref|NP 385391. 1| [Sinorhizobium meliloti] MRALIDMNDTQVEALDTLAKRVRRSRAALIREAIDDYLNRHHREQIEDGFGLWGKRKVDG LAYQEKVRGEW >gi|15965037iref|NP_385390. 11 [Sinorhizobium meliloti] MVGALFDTNILIDHLNAVPQAHKELDRFENRAISIITWMEVMVGADAELVEPTRRFLDGF ETIALNDEIANRAVTLRRAH RIKLPDAVIWATAQTAGRLLVTRNTKDFPADDPGIREPYAV RIKLPDAVINATAQTAGRLLVTRNTKDFPADDPGIREPYAV >gi|15965370ìref|NP_385723. 1 [Sinorhizobium meliloti] MPTSTITSKGQITIPAKVRIDMGLSAGDRVDFIRMEDGHYAWPASHSIRSLKGIVPRPDR PVSLEDMQKAIIAGAAGE >gi|15965369|ref|NP_385722. 11 [Sinorhizobium meliloti] MIGVDTNLLVRYLAQDDTTQSPLASQIIDGFTPEAPGYISQWLVETVRVLTRSYRMSREA VASVIETLLRAREIWDRA DAGYLALATYRATKADFSDALIAHGGLLAGCTETLTFDKLAADHAGMRLVSP >giI15966170IrefINP 386523. 1 NITROGEN REGULATORY PROTEIN [Sinorhizobium meliloti] MPVPLPSSRPKEVKLFRNNRSQAVRIPAEFELPGDRVLIRREGTRLIIEPIARPADIVEL LAEWKKEAPLGPEDRFPDVE DIPARPEKIF >gi15966171IrefINP 386524. 1 NITROGEN REGULATORY PROTEIN [Sinorhizobium meliloti] MNGYLLDTNIISDVIHNPFGPAAQRIERIGPKEIYTSIWASELRYGCAKKGSAKLLAKVE SLLEIVPVLPLDIPADTRY GSIRAELESLGQTIGSNDLLIAAHAYALDLTLVTDNIREFSRVRGLSLENWLER >gill59667101refINE_387063. 11/UNMOWN PROTEIN [Sinorhizobium meliloti]

MEEAVSAADANRKFSLILRSVREGHSYWTSHGRPVARIVPAAKSDNAVSGARTALLSRLE RQPAVIAGRWTRDELYEDE R >gi|15966709|ref|NP_387062. 1| [Sinorhizobium meliloti] MRVALDTNVLAYAEGVNGIEKRDIVLELVRNLPQEAAVIPVQVLGELFNVLVRKAGRSRA DAREAILGWRDAFSIVGTSP EIMVAAADLATDHHFGIWDAVILSAASQAGCRLLLSEDLQDGFTSGGVTVVNPFASPRHT LLESLLGGGEASE ------------------------------------------------------------ ------------- >gi|15967067|refìNP_387420. 1| VIRULENCE-ASSOCIATED PROTEIN HOMOLOGUE [Sinorhizobium meliloti] MPHLARVFQSGNSQAVRLPKEFRFNVDRVEITQEGDALILRPHVEQGEQWSSLKAALARG MSEDFMMCGREQPEQQDRSE LDAVFR >giì15967066|ref|NP_387419. 1| VIRULENCE ASSOCIATED PROTEIN HOMOLOGUE [Sinorhizobium meliloti] meliloti] MISHILDTNAVIALIGRKSDALVTRVLHSPQGIIGLPSWAYELYFGAQKSAKAQHNLETL RLLMADFPILDFDRNDAFV AGEIRAALAAKGTPIGPYDVLIAGQAKARGLTLVTNNVGEFNRVENLRVEDNSL >gil5966439refNP386792. 1 [Sinorhizobium meliloti] MASSTVFISNRSQAVRLPKAVAFPEGVHQVDILKIGRSRVIVPQGKRWDDLFLSGPRVSE DFMSERDQPVAETRESF >gi|15966438|refìNP 386791. 1| [Sinorhizobium meliloti] MLTYMLDTNICIYVMKTYPPAVREKFNGLAEQLCISSITLGELHYGAEKSAWRVENLTAI EHFVARLEVLPFADKAAAHY GQVRAELERTGTPCGPHDMQIGAHARSEGLIWTNNIREFVRMPGVRVENWL ------------------------------------------------------------ ------------ >gi|15892524|ref|NP_360238. 1| unknown [Rickettsia conorii] MSKSARWISSKQWIPKYIRNKLGLHSGSELIINYKKNETLELLPINKDIYSFFGKGKHKA KNGPVDVDEAISIAVIEN DRN >gi|15892523|ref|NP_360237. 1| unknown [Rickettsia conorii] MKLLVLRLSKMIGIDTNILTRTFLEDDKIQGKAAQNFLKNNITSKIFIASYALLEFVWVL KVNKFTRQEIYETVINLIDN SGFIIGHQDIIISATEQYIKGKADFADYIIIAEGEVNSANKFITFDKDLVREVKNASYP ------------------------------------------------------------ ------------- >giìl5892303|refìNP 360017. 1ì unknown [Rickettsia conorii] MRINMAQIIRATEFVRSFSDIMNRVYYKGESFDVQKGNHIVARITPAEIKPSVAVRDLEE AFKNGPHLDPEDADQFMKNR EEIRYNTKQDIKKLVERWD >gi|15892302|refìNP 360016. 1| unknown [Rickettsia conorii] MGLIIDTAIIIALEREKVSTKQWSHYGQTYISPIVLTELLIGVYRVKNENKRIKCLAFIE YVKSLFTILPFGIEEVYTYA RITHDLYTQRITIGTHDMLIAATAITKGFLILTLNVKDFKRIQGLEVLTVSSKD >gi|15893242|ref|NP_360956. 1ì unknown [Rickettsia conorii] MNKWQLHEAKNKLSNIIDIAMHGTPQCITKRGEEAWIISIKDYKQLTKQKPDFKEYLLSI PKTDNLDIQRAKGYARDFE L >giìl5893241|ref|NP_360955. 1| similarity to plasmid stability protein [Rickettsia conorii] conorii DKEICEEWGELMSIDSTNAIDALIAAQAKQSNMILVTRNIKHYNMFNIKIFDPFN DKEICEEWGELMSIDSTNAIDALIAAQAKQSNMILVTRNIKHYNMFNIKIFDPFN >gi|17547775|ref|NP_521177. 1| PROTEIN [Ralstonia solanacearum] MQVSKWGNSLAIRLPAAWEALQLHEGDDVEWIAGERSFGVRRKRAARELFDRIHQYRGKL PADFIFERDQANARD >gi|17547774|ref|NP_521176. 11 TRANSMEMBRANE PROTEIN [Ralstonia solanacearum] MPATEAFFDSNWLYLLSADTAKADAAETLLMTGGWTVQVLNETTHVMRRKLAMPWHAIET VQEAVRAQCRVEPLTLET HDLGRRIAERYGLSVYDALIVAAALLAGCNVLYSEDMQHGLVIEQHLRIVNPFPARA ------------------------------------------------------------ ------------- >giì17545591|ref|NP_518993. 1| PROTEIN [Ralstonia solanacearum] MQSWQMQAAKARFSDWKRAADDGPQEITVHGRPVAWISRALFDRLSGSGESLVSFMRQSP LADQDDWFERERSLPRE VEF >gi|17545590|ref|NP_518992. 1ì PLASMID STABILITY-LIKE PROTEIN [Ralstonia solanacea- rum] MSYLIDTNVLSELRRKAPDARVAAWMQDRPRQSLYLSVLTLGEIRKGIERLEDAVRRQNL IDWLEVELPNYFLGRLLDID AHTADRWGRLMSSAGRPLPAIDGLLAATALQHDLTLVTRNTKDFAGLDIQLINPWEA >gi|30249350|ref|NP_841420. 1| [Nitrosomonas europaea ATCC 19718] MQVSKWGNSLAVRLPASWEILDLKEGDSIEIHVAGARDIEIMKTPEAREILERLRKYRGR LPKDFKFDRLEAHERS

>gi|30249349|refìNP_841419. 1| [Nitrosomonas europaea ATCC 19718] MKDHSAFLDTNILLYLLSEDETKSVRAENTIAAGGFISVQVLNEFASVARRKLNMSFAEI QEFLSHIRMICSWPVTVEV HDQGLRIAEHYGFSIYDALIIAAALSADCTILYSEDMQNSQIIDDRLLIQNPFA ------------------------------------------------------------ ------------- >gi|30250109|ref|NP_842179. 1| protein [Nitrosomonas europaea ATCC 19718] MERGMTMSTIERLYKLSSTLPPAALAELLDFAEFLHQKNMLPQPDEPFRLIDMAGGLEHS ACFAGEPLAVQEALRREWD >gi|30250108ìref|NP_842178. 11 protein [Nitrosomonas europaea ATCC 19718] MNGIDWLLDTNFILGLLKSNPETLSMISNQQIDTRRCGYSAITRMELLGFPGLTAEEEIL ISGKLACLQYLPLTKEIEDM VIGLRRSHRVKLPDAIIAASALTCNAQTDP >giì30248512|ref|NP_840582. 1| NtrP protein [Nitrosomonas europaea ATCC 19718] MFRNRSNTMLSERYVRLFRNGKNQAVRIPREFELNAQEVIMRREGNRLIIEPVPPKGLLW LAELAPLEENFSDIDTRLA PLDDIDL >gi30248513ref) NP840583. lj PIN (PilTN terminus) domain [Nitrosomonas europaea ATCC 19718] MISPRYLLDTNILSDLVRYPQGVIARRIEEVGEAAVCTSIIVAAELRFGAARRNSLRLTR QVEAILAAIEVLPLDTPVDR AYAQLRWVLEQSGQVIGPNDMLITAQAMASQCVLITANLDKFSRVGELQVENWLVR ------------------------------------------------------------ ------------- >giì30249061|refìNP_841131. 11 plasmid stability protein [Nitrosomonas europaea ATCC 19718] MATMTIRNIDEQLKARLRVRAAMHGRSMEDEVQDILRTALSAEPVQTVSLVEVIRSRIEP LGGIELNLPEREAIRDPLEP GA >giì30249060|ref|NP_841130. 1| PIN (PilT N terminus) domain [Nitrosomonas europaea ATCC 19718] MIVLDTNVLSEILRPVPDTQVLVWLAAQPRSVLFTTTVTRAELFYGVRLLPDGQRQTALL DAIQSIFDQDLAGHVLNFDS TAADTYAKIAASRKAVGKPISQFDAMIAAMAKSKGASLATRNLKDFVDCGIDLVNPWSTS YLK >gi|30249551|ref|NP_841621. 1| plasmid stability protein [Nitrosomonas europaea ATCC 19718] MATLTIRNVDDVTKRLLRIRAAQHGVSMEEEVRRILRQELSRAGSSQFPFGQHLLSRFAE STSKEFALPARQVPRTPPSW DEPI >gi|30249550|refìNP_841620. 1| PIN (PilT N terminus) domain [Nitrosomonas europaea ATCC 19718] MILLDTNVLSEFMRLQPATQWVWLDRQAPNEIWTNAVSRAEIELGLALMPESKRQKSLSQ AARTMFDEDFAGRCLPFDE IAASYYGRIVSTRTRMGRPISVEDAQIAAIALAYRMFLSTRNTVDFEDIAGLNVINPWET EA ------------------------------------------------------------ ------------->gi|30248493|ref|NP_ 840563. 1| [Nitrosomonas europaea ATCC 19718] MYTGTVFENNRTQAVRLPVDVRFADDVKKVWVRKLGKERILTPVDHTWDSFFLAEQGVSE DFLSERASQEQQEREVF >gi|30248494ìref|N2_840564. 1 PIN (PilT N terminus) domain [Nitrosomonas europaea ATCC 19718] MLKYMLDTNIAIYVIKRRPIEVLVTFNRYADMMCVSAVTEAELLHGAEKSRQREHNLRQV ADFLSRLEVLSYTSKAAGHY GDIRADLERKEKPIGVNDLHIAAHARSEGFILVSNNLREFERVDGLRLENWIT >giì30250051|ref|NP_842121. 1| protein [Nitrosomonas europaea ATCC 19718] MHVWPVQDAKARFSEFLDACITEGPQIVSRRGAEEAVLVPIGEWRRLQAAARPSLKQLLL SDSARTEMLVPERGKARRRQ VEPLR >gi|30250052|refìNP_842122. 1ì PIN (PilT N terminus) domain [Nitrosomonas europaea ATCC 19718] MYLLDTNWSELRKPRPHGAVLAWINSVDDASLHLATVTLGEIQAGIELTREQDPAKAAEI ESWLDLVSDSYNVLVMDGP AFRCWAKLTHKKSNTLIEDAMIASIAKIHGLTWTRNVSDFSSFGVRIFNPFEFNANA ------------------------------------------------------------ ------------- >gi|30249329|ref|NP_841399. 1| [Nitrosomonas europaea ATCC 19718] MTAATLTSKGQITIPAAVRAGLGIDVGDRVEFIEIEPGRYEVIAATQSVKALKGIIRKPN HPISIEQMNAAIAREAVKSV R >giì30249328|ref|NP_841398. 1| [Nitrosomonas europaea ATCC 19718] MIGLDTNVLLRYLAQDDAIQSPKSTLLIESLSVEEPGFVPLIVIVESVWVLSSAYGSTRE EITEVLHNLLRTRELRIEQA ETVAAALHLYQRGKADFADCLIERTAMRAGCKAVMTFDKTAVKSCGMQLID ------------------------------------------------------------ -------------

>gi|29654595|ref|NP_820287. 1| protein [Coxiella burnetii RSA 493] MLRILAGSIGIGIFSSIMYNYIYTYLEANMKASILDLRYNMKSVLKALERNEEIEILYHG KVKGTILPYRKPSSKKKITE HPFFGMLANEEKSVTEQMDTLRGGRYNDL >gi|29654594ìrefìNP_820286. 1| PIN domain protein [Coxiella burnetii RSA 493] MIFDTDILIWVQRGNVKAAGLIEKAEERMISIYSYMEMFQCATAKSQHKIMHAFLREYDF KIQPLSEKIGHRAAIYIEEY ALPSGLRAGDAIIAATAVENNNVLATSNNKHFKCIKDLQFNLFKP >gi|29654541ìref|NP_820233. 1| transcriptional regulator, CopG family [Coxiella bur- netii RSA 493] MIRTQIYLTKQERKYLNLLSQKIGKSQSALIREAIDQFIKAHLKARDDHQAAMEAAKGLW ADRKDLSNLTKIRKELDNRL KDTE >gi|29654540|ref|NP_820232. 10 PIN domain protein [Coxiella burnetii RSA 493] MLLLLDTDIIIDFLRGQESAVKFIEKTAAKWCHISTLTIAELYVGARDGEEYGVLERFLQ IFTAIEVSPQIAQLGGLFR RDYGKSHGTGLADAIIAATTQCISAKLVTLNKKHYPMLKNIHVPYLKS >gi|21245026ìref|NP_644608. 1| plasmid stability protein [Xanthomonas axonopodis pv. citri str. 306] MPSFTVRNIPDDVHRAIRARAALHGRSTEAEIRAILELAKPADRVKLGSLLVSIGRDAGL TAKEANAFDKLRGKAAIKP IGLK >gi|21245027|ref|NP_644609. 1| plasmid stability protein [Xanthomonas axonopodis pv. citri str. 306] MILLDTNVISELWRPQPNPQWAWIDAQAVETLFLSWTVAELRFGIAVMPKGRKRSTLHAR LEGEVLPLFDGRLLAFDL DASHAFAALASKARTAGLTLGRADAYIAATAAAQGLTVATRDTAPFEAMALDVINPWS >gi] 21242923) ref) NP642505. lj cell growth regulatory protein [Xanthomonas axonopodis pv. citri str. 306] MAMQVAKWGNSLAVRLPSSLVEALELREGDDIEIWDDPRLFAVRKKPGPEAMLERLRAFR GKLPADFKFNRDEANGRG >gi|21242922ìrefìNP_642504. 11 [Xanthomonas axonopodis pv. citri str. 306] MFLDSNWLYLLSEDAVKADGAEALLQRRPVISVQVLNEVTHVCVRKLKMGWDEVGQFLAL VRSFCKIVPLTVDVHDRAR QLAERHQLSFYDACIVAAAAIEGCQTLYSEDMHHGLIIEESLSIRNPFNV ------------------------------------------------------------ ------------- >gi|21231084|ref|NP_637001. 1ì [xanthomonas campestris pv. campestris str. ATCC 33913] MHYNAKHQPWIARQTIMTTLTVTARGQVTFRKDVLQHLGIRPGDKIELNLLPDGRGVLKA ARPAGTIASFVGLLAGRTQK VATIEEINEAAAQGWAGKQ >giì21231085|ref|NP 637002. 1| [Xanthomonas campestris pv. campestris str. ATCC 33913] MKVAADTNVLVRAWRDDPAQADVAAAVLTDAELIAVALPCLCEFVWVLLRVYGFQQADAA SAIRALLAkANVEVNRPAV EAGLLVLDAGGDFADGVIAYEGNWLGGETFVSFDKKAWLLTAQGQSTRLL >gi|15838191|refìNP_298879. 1| plasmid stabilization protein [Xylella fastidiosa 9a5c] MNMAMLTVRNLPDEVHRALRVRAATHGRSTEAEVREILTNMVKPDERVRIGDALATLGRE IGLNNEDFTTFDKVRDKTQA EPMRFE >gi|15838190|ref|NP 298878. 1ì plasmid stabilization protein [Xylella fastidiosa 9a5c] MIVLDTNWSEAMKPEPDAAVRTWLNEQMSVTLYLSSVTLSELLFGIAVLPTSKRKDMLAR TLDGLLDLFNERVLPFNTD AARHYAELAVKARNSGRGFPTPDGYIAAIAASRGYIVASRDTSAYESSGVQVINPWQYSK QT ------------------------------------------------------------ ------------- >gi|16272274|ref|NP_438486. 1| virulence-associated protein B [Haemophilus influenzae Rd] MLTKVFQSGNSQAVRIPMDFRFDVDTVEIFRKENGDWLRPVSKKTDDFLALFEGFDETFI QALEARDDLPPQERENL >gi|16272275|ref|NP_438487. 11 virulence-associated protein C [Haemophilus influenzae Rd] Rd] YGKWANTLKKQGRPIGNNDLWFACHALSLNAVLITHNVKEFQRITDLQWQDWTK YGKWANTLKKQGRPIGNNDLWFACHALSLNAVLITHNVICEFQRITDLQWQDWTK >gi|16272886|ref|NP_439109. 1| protein [Haemophilus influenzae Rd] MIEASVFMTNRSQAVRLPAEVRFSEEIKKLSVRVSGSDRILSPLNQSWDSFFLNDQAVSD DFMNEREIAFQPEREAL >gi|16272885|refìNP_439108. 1| virulence-associated protein C [Haemophilus influenzae Rd] MLKYMLDTNIVIYVIKRRPLEILSRFNQNAGKMCVSSITVAELYYGAEKSEYPERNIAVI EDFLSRLTILDYQPKHAAHF

GNIKAELSKQGKLIGENDIHIAAHARSEGLILVSNNLREFERVIALRTENWV ------------------------------------------------------------ ------------- >gil28868263lreflNp-790882. ll virulence-associated protein, [Pseudomonas syringae pv. tomato str. DC3000] MEQSTVFKSNRSQAVRLPKAVALPDDVKRVDWAVGRTRIISPAGEMWNSWFDGESVSDDF MAEREQPVEQLRESL >gì|28868262|ref|NP_790881. ll virulence-associated protein, [Pseudomonas syringae pv. tomato str. DC3000] MLKYMLDTNICIFTIKNKPVSVREAFNLHHGQLCISAITLMELVYGAEKSSSPERNLAWE GFAARLELLPYDSDAAAHT GMIRAELARAGTPIGPYDQMIAGHARSLGLWITNNQREFQRVEGLRVEDWVSQ ------------------------------------------------------------ ------------- >gi|28869204, ref|NP_791823. 1| prevent-host-death family protein [Pseudomonas syringae pv. tomato str. DC3000] MTTTLSSREFNQDTSGAKKAANEGPVFITDRGRPAHVLLSIEAYLQLTGSAASIADLLIM PTHLDIEFEPQRAVITPRPV DLS >gi1288692031refiNP-791822. 11 PIN domain protein [Pseudomonas syringae pv. tomato str. DC3000] MFLLDTNVVSELRKRNADANVLRWSRTQMASSLFISSITILELETGILRVERRDPTQGAA LRMWLDHHVLKAFAGRILPI DTQVAKRCAQLHVPDPRSECDALIAATALVHGMTWTRNTADFKSSGAALLNPWISQLNEE TAYYSSASR ------------------------------------------------------------ ------------- >gi} 16766336|ref, NP_461951. 1| cytoplasmic protein [Salmonella typhimurium LT2] MHTTLFFSNRTQAVRLPKSISFPEDVKHVEIIAVGRSRIITPVGESWDSWFDGEGASTDF MSTREQPAVQEREGF >giìl6766335|ref|NP_461950. 1| nucleic acid-binding protein, contains PIN domain [Salmonella typhimurium LT2] MLKFMLDTNTCIFTIKNKPEHIRERFNLNTSRMCISSITLMELIYGAEKSLAPERNLAVV EGFISRLEVLDYDTQAAIHT GQIRAELARKGTPVGPYDQMIAGHAGSRGLVWTNNLREFERIPGIRIEDWC ------------------------------------------------------------ ------------- >gi|16761811|ref|NP_457428. 1| protein (assiciated with virulence) [Salmonella en- terica subsp. enterica serovar Typhi] MHTTLFFSNRTQAVRLPKSISFPEDVKHVEIIAVGRSRIITPVGESWDSWFDGEGASTDF MSTREQPAVQEREGF >gi|16761810|ref|NP_457427. 11 protein (assiciated with virulence) [Salmonella en- terica subsp. enterica serovar Typhi] MLKFMLDTNTCIFTIKNKPEHIRERFNLNTSRMCISSITLMELIYGAEKSLAPERNFAVV EGFISRLEVLDYDTQAAIHT GQIRTELARKGTPVGSYDQMIAGHARSRGLWVTNNLREFERIPGIRIEDWC ------------------------------------------------------------ ------------- >gi|16762401|ref|NP_458018. 1, CopG-family DNA-binding protein [Salmonella enterica subsp. enterica serovar Typhi] MSMMAGMDMGRILLDLSDDVIKRLDDLKVQRNLPRAELLREAVEQYLERQDRAETTISKA LGLWQGCEEDGVEYQRKLRE EW >giìl6762400|ref|NP_458017. 11 protein [Salmonella enterica subsp. enterica serovar Typhi] Typhi] RQEYGMKLPDAIILATAQVHRCELVTRNTKDFADIPGVITPYHL RQEYGMKLPDAIILATAQVHRCELVTRNTKDFADIPGVITPYHL >gi) 29143295JrefJNP806637. l) protein [Salmonella enterica subsp. enterica serovar Typhi Ty2] MHTTLFFSNRTQAVRLPKSISFPEDVKHVEIIAVGRSRIITPVGESWDSWFDGEGASTDF MSTREQPAVQEREGF >gi|29143294|ref|NP 806636. 1ì protein [Salmonella enterica subsp. enterica serovar Typhi Ty2] MLKFMLDTNTCIFTIKNKPEHIRERFNLNTSRMCISSITLMELIYGAEKSLAPERNFAVV EGFISRLEVLDYDTQAAIHT GQIRTELARKGTPVGSYDQMIAGHARSRGLVWTNNLREFERIPGIRIEDWC ------------------------------------------------------------ ------------- >gi|29143889|ref|NP_807231. 1| CopG-family DNA-binding protein [Salmonella enterica subsp. enterica serovar Typhi Ty2] MSMMAGMDMGRILLDLSDDVIKRLDDLKVQRNLPRAELLREAVEQYLERQDRAETTISKA LGLWQGCEEDGVEYQRKLRE EW >gi|29143888|ref|NP_807230. 1| protein [Salmonella enterica subsp. enterica serovar Typhi Ty2] MVKGSALFDTNILIDLFSGRIEAKHALEAYPPQNAISLITWMEVMVGAKKYHQENRTRIA LSAFNIIGVTQEIAERSVIV RQEYGMKLPDAIILATAQVHRCELVTRNTKDFADIPGVITPYHL >gi24215974Jref) NP713455. lj protein [Leptospira interrogans serovar lai str. 56601] MKNITFRADDQLLEKARLRAASERKSLTDVFNEFLKNYSNSVKDVSDYENLLQKLAYVKV GRKFTREEMNER >gi|24215973|ref|NP_713454. 1| [Leptospira interrogans serovar lai str. 56601] MKDKVFLDTNLFIYNFDTENKTKHEKSKEIVLTALAENNYVISYQVIQEFSNVALKKFQI PLKPKDLAIYLKRVMFPLCN VYYTNENILNAIEIRNRYKLSFYDSVLIGSAIEANCKTLLSEDLQDGLQIKGLQITNPFN STIKKKK ------------------------------------------------------------ ------------ >gi|24213702|ref, NP_711183. 1| virulence associated protein B [Leptospira interrogans serovar lai str. 56601]

MQTAKLFINGRSQAVRLPKEFQFTGDDVLIQKVGEAVILVPKNKAWNVFLEGLNGFSDDF FKEEREQPKSDKREKL >gil242137011refINE_711182. 11 virulence associated protein C [Leptospira interrogans serovar lai str. 56601] MYLLDTNICIFLIKKKNATLLENLKKKLNKDLFVSSLTVAELEFGIQKSEFKEKNKVALI EFLTIFNILSFSDKDAESYG IIRADLERKGNVIGSIDMLLAAQAIANNYIFVTNNTKEFKRIKALKIENWTQ ------------------------------------------------------------ ------------- >gi|15807097|ref|NP_295826. 1| protein [Deinococcus radiodurans] MTAPKELHERIDRLPPEAIKAIQELVERQEYAAQQIAALKAFAADWTPEEQAAWDEGTKR RPWRTFPPEEV >gi|15807096|ref|NP_295825. 1| plasmid stability protein, [Deinococcus radiodurans] MLALDTNILIALQKLEPAAFGHDRQALMTVPWIPSVVRYEARRSLLAPQYARRLAQLDQL LSGHATLDFDQQAADIAAD IYHQLCTTGQLIDEADLMIAALSIQHGAALVTRNTSHFQRIPGLTLLDWL The following sequences were found in a later supplementary search: ------------------------------------------------------------ ------- >vapB|14600379 : cl99314-199072, length 81, Aeropyrum_pernix, VapB MLLLWSTVSKVIRVKYEKGVLKPLEPLDLQEGEEVQVIIQPGEPIAEKYYGIARKHRPN LDKKEFLEVLEEIEDEDIRGH >gi|14600586|ref|NP_147103. 11 hypothetical protein APE0273 [Aeropyrum pernix K1] MRIFVDTSIILAFLAGQDDRAKDLMRKVERHEITGYINPLVIDEVIHGYLRLATGLSARR IRKLLARRDERLIKMIKGEV WPVLKLFTTLPLMAEPGEIIEFIEEYGLMPADALIALTCKQHELDTIATLDEDFKRIPWL KWP >gi|14600594|refìNP_147111. 1| hypothetical protein APES010 [Aeropyrum pernix K1] MELRRVEIGMSKVIRVRYEKGVLKPLEPVNLEDGEEVDIIIRENLAELARRIRRRLSQER EEPSEILSRERSRLA >gi14600593refJNP147110. lj hypothetical protein APE0279 [Aeropyrum pernix K1] MVECIERHSISVYAPRLFLVEVAGVLVRYLAPSIVERVLDAFSSKVILVGDEAYFRIAVE IALATGSRGADSYYLGLAKT LNLPVATSDKVQAQNARKAGIKSFYILSNNELEELMKYMGCK ------------------------------------------------------------ ------- >vapB|14600379 : c697607-697245, length 121, Aeropyrum-pernix, VapB MAMNIDGDGWWSTTAGSTAYSLSGGGPIIDPRLDVIVLTPLNPVQLFLRSIWPSGSRV TVEASVYSNPLWNIDGQYVYELEPGGIVDIERCGSGVRIARFRWWEDYYERLYTRLLAY W >gi|14601184|ref|NP_147716. 1| hypothetical protein APE1098 [Aeropyrum pernix K1] MRGSTQGCSPTGREAIVLDTGAFIAGKAAALPGRLATPPRVLEEVRDRGSRSLLELLQST GRLEVLAPSTRALERAREEA RRAGVLGRLSGADLEVLALALDLAWQGCRVAVATDDYTLQRLAARLGLGWRLRYRGAV ------------------------------------------------------------ ------- >vapBI14600379 : c760494-760258, length 79, Aeropyrum-pernix, VapB MGWGCAMSKVIRVKYEGGVLKPLEPLVLSEGEEVEWIRRRVFGEEDYRELVDFLSELPK GKAELLDLVEELYLEEALR >gi14602203reflNP_147786. 1I predicted nucleic acid-binding protein, contains PIN domain [Aeropyrum pernix K1] MRRLFVDANIFIRIIFNREHSLLEYLIGTEPYTSTHLLEEAAYKLIALSIIESEGPVSVY KIGKLFEKGAAEDTIRARLA ALDKIAEKLNIIPPTYSDFRESMKISLEYKLLPSDALTVAIMKREEIKEILTLDNDFKQI P >vapBìl4600379 : cl008442-1008167, length 92, Aeropyrum-pernix, VapB MVPPGHDPNDFARGSIKTCQWRGRNINTNIKNTTMGEAVATKKITIEVEVPEDFDEERGV ERLIELLRKGAPLGVKQKDLRRQRIYASRTRY >gi|14601503|ref|NP_148042. 1| hypothetical protein APE1588 [Aeropyrum pernix K1] MPAGLDTNILIYAMDNKAGEKHEKAVEVIEQALKHPTEYIVSSQVLAETIYAVKRKYPAA TPLAQTLAYTLTRTLRWHY THLEVLQASQSPPRYFWDRLLAYTYLNNGADRIITEDEKPYRGILKTIDPFR >vapB|14600379 : cl508755-1508399, length 119, Aeropyrum-pernix, VapB MAIGTQLDPSVTKADNLVGNWGKPGELPEPLTTLRIEHHLLEKWGMKEEARVEPIRRG EMLMLSVGTATTLGWTRAGKDEIEVQLRRPWTWPKARVALSRRIMGRWRLIGWGLIK >gi|14602022ìref|NP_148567. 1| hypothetical protein APE2366 [Aeropyrum pernix K1] MAQGEGGPEQEDNGEVEAHRLGAHKVWLLDSNTLILMASGRIAPSMILEAINSSFKPATT STWAELRGLAEIHRTRLL GRRAQTALRLLQQMGVEVIETESRDADDSLEEAAEKLKVEGAKVYVATSDRSLRRRLRRR GVPTIYYRSSEARLEADWWD DL DL >vapB|14600379 : cl666639-1666448, length 64, Aeropyrum_pernix, VapB

MSKVIRVRYEKGVLKPIGEWLREGEELEWWRKSFRGFKDEAGKYMFKADRDTVKEFV EERR >gi|14602179|ref|NP_148728. 11 hypothetical protein APE2616 [Aeropyrum pernix K1] MIDTSVFADYYLLYPGDPERHERSRTVLDKLSLRDVIVYEPFLFEIELRAVLVRRIPPEQ ALRIVDTTLKHVNVVREEEL HDKAAEIALITGCRAVDAYFIATAKHVDGILITNDKVMKDNAQKIGVKAYYLLDNQDYTK L >vapBI15282445 : 203338-203605, length 91, Aquifex_aeolicus, VapB MICMVGKDEIWKVLPKGQITLPKRIREKLGIREGDILIVEEKEGKLEIRKPKSLRDFYG FLKGKKSINRENIERVIEEWKERELEKDSR >vapC|15282445 : 203579-203860, length 94, Aquifex_aeolicus, VapC MNLKKIWDTSVFIRLFTRNDEKKFEKAEKLIDDASKGKIQLFVPFIWAEIVWVLEKVY KVNRENIRDWEALINTRPRSNYSIGKLYSFFYV KVNRENIRDWEALTNTRPRSNYSIGKLYSFFYV >vapB|15282445 : 1338522-1338839, length 166, Aquifex_aeolicus, VapB MNKRFEQVDKRFEQVDKRFEQINNELNRLIQIMVGIFAGQIALVAAVIGFAWWDRRTIIR KSKEETFEEMEKELRPEKFKKLLNALREKAKTDKELEAILKKYGLL >gi|15606926, ref|NP_214307. 1| hypothetical protein aqqy06 [Aquifex aeolicus VF5] MKLLDTTVLLDFLSGEEEKVETIEQFFEELSQKGEKLFVPEEVIIELVYFLEHGYKWERE DIYEWETILNDELFNVELK PFIREAIKLYSKRQGTFLDCLKSVKAKKMGIKEWSFGRRFKKLGFKTVNPYEES ------------------------------------------------------------ ------- >vapBJ11497621 : c271532-271335, length 66, Archaeoglobus_fulgidus, VapB MPRVIEVIYENGMFKPLEKVDLPEGSRFKILIEDFSEIDRIHEHVKKIAGEASKEKILEL LDEVWI >gi) ll497909refNP069131. l) hypothetical protein AF0293 [Archaeoglobus fulgidus DSM 4304] MDLVYLDSSVIVELLLGSEERRRTIKSLIAGKRRFTSAISYGEVLYWLAISAEKYYGSRG RNAVRKFVKEKHDHYITLH ESVCRTYSSLNIDTLAHPKVETLSVLIRKYNLLPRDLIHITTAIEGNCNAFLTLDEDFKQ VKENINWIIE ESVCRTYSSLNIDTLAHPKVETLSVMRKYNLLPRDLIHITTAIEGNCNAFLTLDEDFKQV KENINWIIE >vapB|11497621 : 287426-287674, length 83, Archaeoglobus_fulgidus, VapB MSNQKRLQPKPISSFMQTNNMPKVIEAIYENGVFKPLQKVELREGEKVKVIVDRGLTQLF GMFRHRRKTDLDEDMDLMITERA >gi|11497927|ref|NP_069149. 1| hypothetical protein AF0313 [Archaeoglobus fulgidus DSM 43041 MKVFFDTSFFVEYFRGNENARRIYEELKNYEYFTSLNWEETTYILMKFTASDFVKLEKHY EVIKKLKEDSNVYEKSLKN AKLFYSSILHDGFQILPLPSWDLVLEIMERYRLLPNDALTAATCKHYGIKKIATFDEDFR RVDFLQWEL ------------------------------------------------------------ ------- >vapB|11497621 : 289639-289923, length 95, Archaeoglobus_fulgidus, VapB MFLRLLSLRGNLFLFSDPQSICQKSSKLYMRTELFKPLQKVDLKEGEKIRLRLDERGYID HSLIRELEVLLKNAPKTKIDLRELERLHDVGKMLY >gi|11497932|ref|NP_069154. 1| hypothetical protein AF0318 [Archaeoglobus fulgidus DSM 4304] MSEKCFIDTTVILEVILRKEFKILEKLSEYVLHTSVNVLEEASFKIIFVSWDELSVSRVN IFKVKDSFEKGIGSSLTET RLHALNVLKDALKIIETDEHIFDMAKKIILEYKLLPNDALIAATCKHYGIKKIATFDEDF RRLDFLEVLGL RLHALNVIKDALTCIIEIDEHIFDMAKKIILEYKLLPNDPI, IAATCKHYGIKKIATFDEDFRRLDFLEVLGL >vapB|11497621 : 290594-290764, length 57, Archaeoglobus_fulgidus, VapB MSMEKIFIDTNVIIDLLRGKKSWSFFRDVEDGEIHGLTNKNGVSGNCLRLPDPYNG >gi|11497934|ref|NP_069156. 1| hypothetical protein AF0320 [Archaeoglobus fulgidus DSM 4304] MFLETVYVYLILTTDKGPLTLRKRPELIENVNLEPVLRVFEIIDMLPTDRIAKEYIVELI GKFGLLPNDALIAATCKHYE DFRQVDFLEWEP DFRQVDFLEWEP >vapB|11497621 : 350180-350689, length 170, Archaeoglobus_fulgidus, VapB MVNVTFENDDVGHVAAAIAVNGTYFILDQHLPPFDPQGYFIKWLRDGKRIEKAEIIDNNT TIPLNLSIGYVASDRDAKSLESRIRQYFKGTGIREDPRLNGEKLPLGYREGYTLKLSLEM AEYYHPEFERQYAEHIYKLLEESIEGRFKAFNLHLSIKGDVMEIVLYLAR

>gi|11497997|ref|NP_069221. 11 hypothetical protein AF0386 [Archaeoglobus fulgidus DSM 4304] MKCVEVHVIDSSAIFQRKAVYRNMVTVPEWAEILDEASALYFSVKNFRVEEASPESVEEV KEAARKTGDIHKLSDTDIK VLAKALDEIKKGNEWVLVTDDYAIQNVAMSLGIRFDGILHRQISKEFKWVKVCRGCGRRI ESEICPVCGSEAIIRRVKND KNRNSG KNRNSG >vapB|11497621 : c534011-533655, length 119, Archaeoglobus_fulgidus, VapB MGIATKLDPTLTKSDALVGNWGHPGNLPDVLTSFTMEVNLLERWGLDEEMEVEKIKMN EPLMLAVGTAITLGWTSARDDIVEVKLRRPVCADKGSRVAISRRVGSRWRLIGAGIIR >gi|11498199|ref|NP_069425. 11 hypothetical protein AF0592 [Archaeoglobus fulgidus DSM 4304] 4304] VETESEGDPSLIEAAEKYGCILITNDKELKRKAKQRGIPVGYLKEDKRVFVELLD VETESEGDPSLIEAAEKYGCILITNDKELKRKAKQRGIPVGYLKEDKRVFVELLD >vapB|11497621 : c556664-556485, length 81, Archaeoglobus_fulgidus, VapB MGKVIQIEVPDRVNEKLINKLKEMLADKILDEIGKDYADIDLYNLYLTLKFPKTEDVTFD TDKELEYLRKMKEKEKKRVWS >gi|11498226|ref|NP_069452. 1 hypothetical protein AF0618 [Archaeoglobus fulgidus DSM 4304] MEKNLYDTNKLIELYKNKESMSGYTTILNVIEFPKALEFNLTVLYLSKSDYRLAIKISTE LLKIGEPVPAVYTLISAIAN KQRFKGCNAGQTFYAS KQRFKGCNAGQTFYAS >vapB, 11497621 : c981711-981451, length 87, Archaeoglobus_fulgidus, VapB MANLIHTKPFSSFSANHQHAKNHRSCLRKRSLQAFAEGGFEGGGENKASHRGGNRRRYKG IQQKSRPRRFGGIPKGEKMIVIDTSVFIDALFRFNEKRSNMANEIFEIAQHRQIAWEPE IFRMEIIGQLVRRTPKSEAITLYEGIV >gi|11498689|ref|NP_069918. 1ì hypothetical protein AF1089 [Archaeoglobus fulgidus DSM 4304] MMRYTVDTSIFADFIFEFDENRTSAAEKVLSEIKGRILNPKVFKVEMTCILSRRFHSEIV EKIISEILEDVALIENPDEI AFEVALKTGSRAIDAYFIATAKLTNSILITNDRIMAENAKKAGIEAYYLLEEFEEVKRRL Q >vapB11497621 : cl236899-1236693, length 69, Archaeoglobus_fulgidus, VapB MRDALGIKPGTVMNVHLEGKKIILEPSPEPPDIFVDLGERSEQILKESRKIDEERMRKLL RDLGVEGGD >gi|11498981|ref|NP_070214. 1| hypothetical protein AF1385 [Archaeoglobus fulgidus DSM 4304] 4304] EWCSTELDVEAAKVKLRYGLALADCYVLALSKLKNCKAVFRKREKEMPDKVEKDFDVIFL EDYVGGDR EWCSTELDVEAAKVKLRYGLALADCYVLALSKLKNCKAVFRICREKEMPDKVEKDFDVZF LEDYVGGDR >gi|11499302|ref|NP_070540. 11 hypothetical protein AF1711 [Archaeoglobus fulgidus DSM 4304] MGEIIEAVYQKGVLKPLRKVSLREGEIVKVEIRETKKVTGRFYAKLRELEKRIERVEGAH RELEEIRDDRY >gi|11499301ìref|NP_070539. 11 hypothetical protein AF1711 [Archaeoglobus fulgidus DSM 4304] MIVIDTSIFVDYLFDRDENRNEKARKFLNSIEGLTVFVPKIFVIELISVAKRLGIEISRK DIEELTYDFEILSEDFVFDE ALNVAEKVHPRAADSYFIATARLTNSILISSDRLMVRNGKKYGIEAYCLLDELEKALEAI GKLKGEG ALNVAEKVHPRAADSYFIATARLTNSIITSSDRLMVRNGKKYGIEAYCLLDELEKALEAT GKLKGEG >vapB11497621 : 1978461-1978667, length 69, Archaeoglobus_fulgidus, VapB MGHGCLRRYFVCDILLIKTDKTEKAIELFNRLNPIASVTVYEESFYTGLRIIAQKRLNIK NMLMLSGIL >gi|11499795|ref|NP_071038. 1| conserved hypothetical protein, C-terminus [Ar- chaeoglobus fulgidus DSM 4304] MDFVKALHNFYDEIYWQDSRDLELIKSVAEKYKSLPNDALIAATCKHYGIKKIATFDEDF RRVDFLEWGL ------------------------------------------------------------ ------- >vapB|11497621 : c980157-979951, length 70, Archaeoglobus_fulgidus, VapB MSGGLSFWRLLNSNFQRNPFLLPRKITDMPKIIEAVYENGVFKPLQKVDLREGEKVKIIA GNLVERLRKYRVKVDSDIVAEFISERR >gi|11500021|ref|NP_071267. 11 hypothetical protein AF1086m [Archaeoglobus fulgidus DSM 4304] MIVIDTSVFIDALFRFNEKRSNMANEIFEIAQHRQIAWEPEIFRMEIIGQLVRRTPKSEA ITLYEGIVXKVKLIDFAVL

NEVAFSVCLETGCRAIDAYFIATAKLANSTLITNDRIMAENARKAGIEAYYLLEEFEKVK KRLQ ------------------------------------------------------------ ------- >vapB|11497621 : c550521-550279, length 60, Archaeoglobus_fulgidus, VapB MLNSQRNMCMPNITLSLPEDLYRKMKKYGEIRWSEWRKAIAEYLEKLEEIETEVGSKEL >gi|11546068|ref|NP_069444. 2| hypothetical protein AF0610m [Archaeoglobus fulgidus DSM 4304] MWADTNLVIERVKKNESIEENITEVTIVEFPPVINYKKFHGKVLIIERGDVLLSIELQRR LRIVRKPRKPFSDLLIASI CINRDEELITKDRDFLDIAEVSNLRVKLIEP >gi, 15888348|ref, NP_354029. 1| AGR_C_1846p [Agrobacterium tumefaciens str. C58] MVYDFENRYTKDFSMRTNIELDDALIAEAMEITGLPTKKATVEKALRDLVENLGRRKALQ ELRGIGWKGDLEEVRGSWSA DSIKSQDAAE >vapC) 15887359 : c1001393-1001007, length 129, corrected start, A. _tumefaciens_Cereon_C58_circ_chr, VapC MIWDTSVWIDWFQNKQTPQVATLSDINDLSDVIIGDIILLEILQGERNERRAAAIESRL KVFELVSMLTPEFAVAAAANYRKLRGLGKTVRKTADLIIGTYCIEHGHKLLQNDRDFQPM ADHLGLQFV ADHLGLQFV >gil5889422ref) NP355103. 1 AGRC3882p [Agrobacterium tumefaciens str. C58] MAMTGDQIDKSWFSQQLKRKGKSQADLARFLNLDRSAVTRMLNGDRNMSVEEQDRIAEYL EIPVGDVALHRRGGVAGFSE NNQTAYSEPAPSGRSGPEAGNVSTTESRHPIFGCMKGTITVMPDVDLTKPVDFEWGEKLY NE >gi|15889421|ref|NP_355102. 1| AGR_C_3881p [Agrobacterium tumefaciens str. C58] MILNGEKSSTMSDGFLLDTCAVIWMSQGEPVSDEAVSALNQSYRAGDPVCVSAVTAWEMG MLVAKGRISETKSPQRWYDD FKREAEVIEQPVTADIFIASCFLPQLVHKDPIDRILITTAREHDLTIITRDRVILAYGEA GHVKTLAC ------------------------------------------------------------ ------- >gi|15891912|ref|NP_357584. 1| AGR_L 3576p [Agrobacterium tumefaciens str. C58] MVTTVLRKFDMTTTVTAKGQVTIPKAVRELLGISPGSSVDFVRAPDGRIVLVRADKKQPL TRFAKLRGHAGEGLGTDAIM ALTRGDE >gi|15891913|ref|NP_357585. 1ì AGR_L_3577p [Agrobacterium tumefaciens str. C58] MTLVDTNVLLDLVTDDPVWADWSIEQLELASVSGSLYINDVVYAELSVRYERIEELDAFV DQAGLKFTPFPRAALFLAGK AFTKYHRGGGTRTGVLPDFFIGAHAAIQNLPLLTRDVARYRSYFPTVTLISPEV ------------------------------------------------------------ ------- >gi|17936025|ref|NP_532815. li Hypothetical protein Atu2241 [Agrobacterium tumefaciens str. C58] MTGDQIDKSWFSQQLKRKGKSQADLARFLNLDRSAVTRMLNGDRNMSVEEQDRIAEYLEI PVGDVALHRRGGVAGFSENN QTAYSEPAPSGRSGPEAGNVSTTESRHPIFGCMKGTITVMPDVDLTKPVDFEWGEKLYNE >vapC|17933925 : c2105391-2105804, length 138, A. tumefaciens_str_C58_U_Wash_circ_chr, vapC MSDGFLLDTCAVIWMSQGEPVSDEAVSALNQSYRAGDPVCVSAVTAWEMGMLVAKGRISE TKSPQRWYDDFKREAEVIEQPVTADIFIASCFLPQLVHKDPIDRILITTAREHDLTIITR DRVILAYGEAGHVKTLAC DRVTLAYGEAGHVKTL, AC >gi|17936725|ref|NP_533514. 1| Hypothetical protein Atu3013 [Agrobacterium tumefaciens str. C58] MVTTVLRKFDMTTTVTAKGQVTIPKAVRELLGISPGSSVDFVRAPDGRIVLVRADKKQPL TRFAKLRGHAGEGLGTDAIM ALTRGDE >gi|17936724|ref|NP_533513. 1| Hypothetical protein Atu3013 [Agrobacterium tumefaciens str. C58] MTLVDTNVLLDLVTDDPVWADWSIEQLELASVSGSLYINDVVYAELSVRYERIEELDAFV DQAGLKFTPFPRAALFLAGK AFTKYHRGGGTRTGVLPDFFIGAHAAIQNLPLLTRDVARYRSYFPTVTLISPEV ------------------------------------------------------------ ------- >vapB|23464628 : 391589-391864, length 92, Bifidobacterium_longum, VapB MIRRLREDPVQAQKADAHDAYPPFFMRAYLITRTASKTTAPHASIMTATRRCIMATLTIR KIPDEQIQQLKEVAEKNNRSMESQVRSILEEWLAGTVAHEITRKTNFYDEIREFMKNMDF EGLDKGELPLSERNSADSRPPVSFE >gi|23464899|ref|NP_695502. 1| plasmid stability protein StbB [Bifidobacterium longum NCC2705] MIILDTNVISEIIKKQPDEHVANWLRNQDTSNLATTAITVAELLAGICRMPEGKRRKYTD TTVKLALMTLEDRTFAFDTQ

AAADYAHILVEREHRGTPTSIQDAMIAAIACSWDAAIATRNIKDFEGTDVELINPWEFA ------------------------------------------------------------ ------- >vapB|23464628 : cl248957-1249274, length 106, Bifidobacterium-longum vapB, a relB/dinJ homolog MTMAMVTARVNAERKRDAEKVLKRNGRTYSDLIRDLTDYLADTGELPEFERLTLSLIQER ERRKKQELIQRFADRNLPEAEGDLSDEEILAQARMERFGGRDETAV >vapC|23464628 : cl248539-1248970, length 144, Bifidobacteriumlongum, vapC MKLLFDTNILLDLCNDKRAPFHKQCVDLLMEAVAQPNIEIMAPVSSLNDVYCVLRKHYGE ERAARDDIGGLMELFDIRPLMERHACMSYRSDEPDFEDGLIRAVAEDNDADVIVTRDVEA FHHSSVRSMDAEQCRALLLADSKA FHHSSVRSMDAEQCRALLLADSKA >gi|23465958|ref|NP_696561. 1| hypothetical protein with possible helix turn helix motif [Bifidobacterium longum NCC2705] MTMVQMNVRIDAKLKNEVEEVLKGKGVSVSDVIRSLWLYIADRKEVPALETTAEEQAREE EKQRKLKLIREGAGYVHKEL VKAGLISEDTDLMEGLTYKQFRDKMYDEQLDTYYNMKRAD >gi|23465959ìref|NP_696562. 1| hypothetical protein BL1399 [Bifidobacterium longum NCC2705] MTDVSMQRILLDTNVLLDYLLHRDDHAKMAEAVMELGAKNNITLLCASLSLKDIAYLSSS AIRREFKPNESEVENFTRGF LSSRVPWRCIEQVKEMCDIVAVDESTCDKAFSLQKRHRDFEDDLIIVAAQQSGANCWTSD AELISHFPEYCKTPAEIVA ALE >gi|15805445jrefìNP_294141. 11 hypothetical protein DR0419 [Deinococcus radiodurans R1] MSDAEGGYTFPMTTLEARIENGKVVLTPEQAAELGLREGEVLPVTIAPHEAETEGNPFTR WIGTLPPLPDGEESARFYRR LRDGE >gi|15805446|ref|NP_294142. 1| hypothetical protein DR0420 [Deinococcus radiodurans R1] Rl] AYGSYAQRRQRSGGGSPRQILSDFVIGAHALYHGAALFTADPQHYRLSFPALTVLTP AYGSYAQRRQRSGGGSPRQILSDFV=GAHALYHGAALFTADPQHYRLSFPALTVLTP >giìl5806541|refìNP_295254. 1| hypothetical protein DR1530 [Deinococcus radiodurans R1] MTRLLVNVELDEQGQPVFQLTPAQLAKLGLSGSAVHVARWEVAAQEAAQPAQSPFRRYVG IAPPLEGGSVEYHRQQLGYE E >giìl5806540ìref|NP_295253. 1 hypothetical protein DR1530 [Deinococcus radiodurans R1] Rl] RAFRGYSVRRRQSGGGQPRRILADFMIGAHALLRADALVTLDPQHYRLNFPELRVINPAE G RAFRGYSVRRRQSGGGQPRRILADFMIGAHALLRADALVTLDPQHYRLNFPELRVINPAE G >vapB|15789340 : c67955-67662, length 98, Halobacteriumsp_NRC_1, VapB MSKAVKVDEDAKSRLEELQAEIRLETGESVTQQELLSRLIDDAYQDREAVIDSFRSSTVP LSDAEKARMVEGRVSSGVEIREEDIDDILYGGPEDV >giì15789405|ref|NP_279229. 11 Vng0072h [Halobacterium sp. NRC-1] MTVLVDTGVLYADHDTDAARHEAAAGALDAVYDGEFGQPYVSDYLYDEAVTLALARSSSF DVAQRLGRRLRGADPYPETY RMLDVTTAVFDDAVGVFERLDDQQLSFTDATTVALMRRHDVDGVLSFDDDFDGLVDRLDP AAW ------------------------------------------------------------ ------- >vapB|15789340 : cl474604-1474407, length 66, HalobacteriumspNRCl, VapB MMGSDGTELGMLYNITMDLKSGTLEHLLVEQTEESVAADFPIGDDGRYRVPVSRVQAVKD YIWRR >giì15790862|ref|NP_280686. 11 Vngl994c [Halobacterium sp. NRC-1] MRVHVPAQDAREAVRQAAATTGDADVLSETDRRLLATAHELDGTLVSDDYAMQNVAAELA VTVESISQDGITERRDWRLQ CQGCGREFDDTDHDRCPVCGSPLERKNPS >vapB|15789340 : cl510923-1510639, length 105, Halobacterium_sp_NRC_1, VapB MPPTWESFEMDVDLLERLVGAADGEQIDDISTGEPLMLTVGTATTVGSVTSARDGECEVA LKRPVCAPAGAKIAINRRVGARWRLIGVGTLTESE >gi|15790906ìref|NP_280730. 1| Vng2054h [Halobacterium sp. NRC-1] MQAVAIDTNALLLPATQPLRLFEELDRLLGDYDAWPQAVHDELVALAAGAGETASAASVG VDLATDRCGTLRTDVSYAD DALHALAVSEDVDAWTNDGPLKERVLDAGTPVIHLRGRTQLTITRP ------------------------------------------------------------ -------

>gi|24213637|ref|NP_711118. 1} Hypothetical protein LA0937 [Leptospira interrogans serovar Lai str. 566011 MKSYPVGELKSHFSEVLESVKNGESVGILYGKGKKPIAMIIPMKSKKEGKRKIGLLYGKV KISFSKGFKISEEEFLS >gi|24213636|ref|NP_711117. 1| Hypothetical protein LA0936 [Leptospira interrogans serovar Lai str. 56601] MKYLLDTHVILWIIGSSNLLSKKAKATIENSENKIYVSSVSLWEISLKFRLGKLSLSGMK PSQIPEILSKSNIETINLES ADASTYGQLKVMHHRDPFDRMLIWQCILRKFTLISKDSKMKKYRSHGLKTLW ------------------------------------------------------------ ------- >gi|13473341|ref|NP_104908. 1| hypothetical protein mll3899 [Mesorhizobium loti MAFF303099] MRVTTKGQVTIPKPIRDHLGIGPGSEVEFVATDGGVRLVPVNENLSHEEKLRRFHDVLDR MEGTLDLGGMTTDQYMEWLR GPREDLDID >gi|13473340|ref|NP_104907. 1| hypothetìcal protein mll3899 [Mesorhizobium loti MAFF303099] MKISTLIDTNVLIDVWGPTGPMKEWSASAIASCRRDGALVWNSIIWSELAPLIATEAALR KAVDMLEMDRELIPWDAAFL AGVTHSRYRRAGGVRERTLPDFFIGAHASVAGHRLLTRDATRYRSYFPDLEIISPDMHP ------------------------------------------------------------ ------- >vapB&15678031 : 202303-202899, length 199, M. thermoautotrophicum, VapB MYVARSFDINKPGADPEHLAGGVIGGSLVQGRLRVGDEIEIRPGIQVKKDGKQTWMSLHS TITGLVAGGEEMEEVGPGGLVGVGTLLDPALTKADSLSGSVAGEPGTLPPVRHSFTMETH LLERWGTKEETKVEPIKTGEPLMINVGTTTTVGWKSARADDADWVLKLPACAEEGQRI ALSRRVGARWRLIGYGIIK >gi|15678290|ref|NP_275405. 1| hypothetical protein MTH262 [Methanothermobacter ther- mautotrophicus str. Delta H] MIPYQFRVDIVSELRRLFPKNDLLVPSFVIGELEGIKRHSGGDARIAASVGLALAKKPPF RIFEEKLLEGETVDDALLRI SDVLCTSDRELRRRARSKGIPVVYLRQKRYLGVDGHILE SDVLCTSDRELRRRARSKGIPWYLRQKRYLGVDGHILE >vapB) l5678031 : 1698784-1698945, length 54, M. thermoautotrophicum, VapB MRFCGNTFSCQPGYHSAALKTLRMETDIHIFAGIFPGAVQLIAFFLFIISGYIY >gi|15679850|ref|NP_276968. 1| hypothetical protein MTH1862 [Methanothermobacter ther- mautotrophicus str. Delta H] MHIDNWFMKKVLDASAFINGYVPEGRENYTVRSVTEEIRDFRSMMILEDALREGRLKITE PDPESMKVVEDAISESGDI MRLSPTDMEVIGLAVSLRGKDDVTVITDDYTIQNTLKILGIGFRSVLTSGIRDTYSWRRV CTGCRRVYPLDYEFEECEIC GSRIVRKRHRN ------------------------------------------------------------ ------- >vapB|15668172 : c846334-846143, length 64, Methanococcus_jannaschii, VapB MISAKSKTKRITITFEIPEDIDAKKFKDDVKRYVRYKLLANKLYELLEGENIEEIEEEIR KRRE >gi|15669104|ref|NP_247909. 1| hypothetical protein MJ0913 [Methanocaldococcus jan- naschii DSM 2661] MKILKKLKKKLEKEESKILVDTSVLIDYFKKRRLEELGGEAISIITAVEFIRGISEHKQE QVLNIFKELFEIVYIDEEII IPFSKIYRQLKKRGMLIDDADLYIACTAIIKNYPLWTKNKKHFERLKEFGLKIYDK ------------------------------------------------------------ ------- >vapB] 15668172 : cl268398-1268213, length 62, Methanococcus_jannaschii, VapB MNESIMQLLYDLTKMNYSALYGEGRYLRIPAPIHYADKFVKALGKNWKIDEELLKHGFLY FI >gi|15669510|ref|NP_248320. 1| hypothetical protein MJ1320 lmethanocaldococcus jan- naschii DSM 2661] MYKIVPDTNFLIYVFKHKINFDYEIERALNTKFEIVILSPIKEELERLLKSRDLKGKEKL AVNLALAKIKNYKLVDYTAN YADEAILNYAKENENVIVATNDKELKEKLMENNIPVMVVRQKKYFEIFGMV >vapB 15668172 : 1445372-1445695, length 108, Methanococcus_jannaschii, VapB MVQGPVIIPLISTLGLSFLAILLAYKISFSVIGFINSTLPTTLFPSKPYMLFVKISTISP LTCPSLIILTPALTWSLTALSMAYLYSSYKPNTFFTLSKNVSSFLTTG >gi|15669666|ref|NP_248479. 1| ribosomal protein S15A isolog [Methanocaldococcus jan- naschii DSM 2661] MLSLPPPEFYKLWIINKSPYQLFNIYRSGIMKVKVLDASAIIHGYNPIIEEGEHYTTPEV LEEIESKKIIVEQALDFGKL KIMSPNREYIKKVEEVVKKTGDNLSQQDIGVLALALNLNAILYTDDYGIQNVAKKLNIEV RGIAFEPTNKDFIWRKICEG CKKLYPVDYEEDICEICGSPLKRKMVKSRLKKKRKKK CKKLYPVDYEEDICEICGSPLKRKMVKSRLKKKRKKK

>vapB20093440 : 1478697-1479293, length 199, Methanopyrus-kandleri-Avl9 VapB MYIARSFDVNKPGTRPSDLKGGVIGGAIVQGEVEIGDEIEIRPGIRVERYGRTEWEPVYT EWSLHANVTPVERARPGGLVGIGTKLDPTMTKADRLSGQVAGEPDTLPPVRHELLLEVE LLERWGTEEERKVEPIRTNEVLMLTVGTATTVGWTSARDDEIEIKLKQPVCAEEGDRV AISRRIQRWRLIGHGVIKG >gil20094884|ref|NP_614731. 11 Predicted RNA-binding protein containing PIN domain [Methanopyrus kandleri AV19] MTIRWLDANFLMIPHQEGVDVFSELDRLLGSYRPIVPRQVLEELERVKRAATGRDKIAAR VALSLVDAKGIEWDVKGR DGDEAILNLARRWDRVYVGTRDKELKKRLWKLGVPVITLRQRTHLVIERG ------------------------------------------------------------ ------- >vapB20088899 : 1173673-1173882, length 70, Methanosarcina_acetivorans, VapB MIFMGSTAEIEKRLIELDKEIHSILNMVRKKEGKSSKEIVESACGAWGYDVESEEFVDQL RKSSRLDWVE >gi|20089859|ref|NP_615934. 1| Pin protein [Methanosarcina acetivorans C2A] MGRMKFFVDTSIFVDCLRKEVIPSSKSFLERIGDEYSGYTSSITVAELSVGAHLSRSQDA LEKTLELLNIVEVIDLDSRI AIDAGKIYADLIRSGKRIELNDCLIAATALSLGINRE AIDAGKIYADLIRSGKRIELNDCLIAATALSLGINRE >vapB20088899 : 4548892-4549509, length 206, Methanosarcina_acetivorans, VapB MDKPASMLIARSFDINKPGASIDEIRGGVIGGTLTEGVLHPGDELEIRPGIKVTTEGSTK WIPIVTTISSIYAGPTKVEEATPGGLLAVGTYLDPTLTKGDSLTGQIAGVPGTLPETRHQ FVMELHLLDRWGVTREEKINEIKTSEPLMLNIGTATTVGIVTSARKNEAQVALKRPISA AVGAMVAISRRIDSRWRLIGVGVIKS >gi|20092491|ref|NP_618566. 11 Hypothetical protein MA3690 [Methanosarcina acetivorans C2A] C2A] LRLAGEMEAAVLTNDIGLKRRLAENGIQTVSLRQKNRLDIV LRLAGEMEAAVLTNDIGLKRRLAENGIQTVSLRQKNRLDIV >vapB|21226102 : 726480-727034, length 185, Methanosarcina_mazei, VapB MEEIRGGVIGGTLTEGVLHPGDELEIRPGIKVTTEGSTRWIPILTTVSSIYAGATKVDEA TPGGLLAVGTYLDPTLTKGDSLTGQMAGVPGTLPETRHQFVMELHLLDRWGVTREEKIN EIKTSEPLMLNIGTATTVGWTSARKNEAQVALKRPISAAIGAMVAISRRVDSRWRLIGV GVIKS >gi|21226697|ref|NP_632619. 11 Hypothetical protein MM0594 [Methanosarcina mazei Gol] MKIIIDTNGFMIPVQFGVDIFEELKRLGFNEFYVPEAWFEIEKLIKREKGSNRTAAKVAR SMMERCMRIAGKGPADDVI LRLAKEMGAAVLTNDIGLKRRLAESGIQTISLRQKNKLDFV LRLAKEMGAAVLTNDIGLKRRLAESGIQTISLRQKNKLDFV >vapB|15839372 : 71570-71806, length 79, M. _tuberculosis_CDC1551, VapB MATIQVRDLPEDVAETYRRRATAAGQSLQTYMRTKLIEGVRGRDKAEAIEILEQALASTA SPGISRETIEASRRELRGG >gi|15839444|ref|NP_334481. 1| hypothetical protein MT0071 [Mycobacterium tuberculosis CDC1551] CDC1551] MDECWDAAAWDALAGKGASAIVLRGLLKESISNAPHLLDAEVGHALRRAVLSDEISEEQA RAALDALPYLIDNRYPHS PRLIEYTWQLRHNVTFYDALYVALATALDVPLLTGDSRLAAAPGLPCEIKLVR >vapB|15839372 : 363648-364106, length 141, M. tuberculosisCDC1551, VapB MPIHSGPGPRGSLGDGGGGRATQRHAAAGTRAVASCCRARCATRQRGRGRPTRGCLGRDS SALLALSPAKIPDIARYHRKMSDVLIRDIPDDVLASLDAIAARLGLSRTEYIRRRLAQDA QTARVTVTAADLRRLRGAVAGLGDPELMRQAWR >gi|15839686|ref|NP_334723. 11 hypothetical protein MT0314 [Mycobacterium tuberculosis CDC1551] CDC1551] EVQTLLADRGHHRGPSIPDLLIAATAELSGLTVLHVDKDFDAIAALTGQKTERLTHRPPS A EVQTLLADRGHHRGPSIPDLLIAATAELSGLTVLHVDKDFDAIAALTGQICTERLTHRPP SA >gi|15839947|ref|NP_334984. 1| hypothetical protein MT0574 [Mycobacterium tuberculosis CDC1551] MLSRRTKTIWCTLVCMARLNVYVPDELAERARARGLNVSALTQAAISAELENSATDAWLE GLEPRSTGARHDDVLGAID AARDEFEA >gi|15839946|ref|NP_334983. 11 hypothetical protein MT0574 [Mycobacterium tuberculosis CDC1551] MRASPTSPPEQVWDASAMVDLLARTSDRCSAVRARLARTAMHAPAHFDAEVLSALGRMQR AGALTVAYVDAALEELRQV

PVTRHGLSSLLAGAWSRRDTLRLTDALYVELAETAGLVLLTTDERLARAWPSAHAIG ------------------------------------------------------------ ------- >vapB|15839372 : 719471-719728, length 86, M. tuberculosis_CDC1551, VapB MVGMSEVASRELRNDTAGVLRRVRAGEDVTITVSGRPVAVLTPVRPRRRRWLSKTEFLSR LRGAQADPGLRNDLAVLAGDTTEDLGPIR >vapB|15839372 : 719471-719728, length 86, M. tuberculosis-CDC1551, VapB MVGMSEVASRELRNDTAGVLRRVRAGEDVTITVSGRPVAVLTPVRPRRRRWLSKTEFLSR LRGAQADPGLRNDLAVLAGDTTEDLGPIR LRGAQADPGLRNDLAVLAGDTTEDLGPIR >gi|15840060|ref|NP_335097. 11 hypothetical protein MT0686 [Mycobacterium tuberculosis CDC1551] MSVTQIDLDDEALADVMRIAAVHTKKEAVNLAMRDYVERFRRIEALARSRE >gi|15840059|ref|NP_335096. 11 hypothetical protein MT0685 [Mycobacterium tuberculosis CDC1551] MAAATTTGTHRGLELRAAQRAVGSCEPQRAEFCRSARNADEFDQMSRMFGDVYPDVPVPK SVWRWIDSAQHRLARAGAVG ALSWDLLICDTAAARGLWLHDDADYELAERHLPDIRVRRWSADD >gi|15840384|ref|NP_335421. 1| hypothetical protein MT0988 [Mycobacterium tuberculosis CDC1551] MKTLYLRNVPDDWERLERLAELAKTSVSAVAVRELTEASRRADNPALLGDLPDIGIDTTE LIGGIDAERAGR >gi|15840385lref|NP_335422. 1| hypothetical protein MT0988 [Mycobacterium tuberculosis CDC1551] CDC1551] WEIRANLSAYDASYVALAEALNCALVTADLRLSDTGQAQCPITWPR WEIRANLSAYDASYVALAEALNCALVTADLRLSDTGQAQCPZTWPR >gi|15841183|ref|NP_336220. 11 hypothetical protein MT1761 [Mycobacterium tuberculosis CDC1551] MSAMVQIRNVPDELLHELKARAAAQRMSLSDFLLARLAEIAEEPALDDVLDRLAALPRRD LGASAAELVDEARSE >gi|15841182|ref|NP_336219. 11 hypothetical protein MT1761 [Mycobacterium tuberculosis CDC1551] MIVLDASAAVELMLTTPAGAAVARRLRGETVHAPAHFDVEVIGAIRQAWRQLISDHEGLW VVNFLSLPVRRWPLKPFT QRAYQLRSTHTVADGAYVALAEGLGVPLITCDGRLAQSHGHNAEIELVA >vapB|15839372 : c2503593-2503357, length 79, M. tuberculosis_CDC1551, VapB MGACEAGRRSRGEDTPVRAAAARLRRAEVEIARRGEPVAKLVPLHPHETRRLGIDHGVYR VPDDLDAPLSDDVLERFHR >gi|15841724|ref|NP_336761. 1| hypothetical protein MT2291 [Mycobacterium tuberculosis CDC1551] CDC1551] YVPDRMRRCGTSPLSVDHAHTAHRRASGSPSTSIRPCAHRPGTAAWPDDHHRRRPVSCL YVPDRMRRCGTSPLSVDHAHTAHRRASGSPSTSIRPCAHRPGTAAWPDDHHRRRPVSCL >gi|15842081|ref|NP_337118. 1| hypothetical protein MT2620 [Mycobacterium tuberculosis CDC1551] MSTTIVAGVIQGHLPVILPTRRRARDLGHTTALFRAQTLQCIYLSIEYLYVCSMSRRTTI DIDDILLARAQAALGTTGLK DRVDAALRAAVR >gi|15842082|ref|NP_337119. 11 hypothetical protein MT2622 [Mycobacterium tuberculosis CDC1551] CDC1551] ELAHVAGLHHRSVKIADLVIAAAAELSGTIVWHYDENYDRVAAITGQPTEWIVPRGTL ELAHVAGLHHRSVKIADLVIAAAAELSGTIVWHYDENYDRVAAITGQPTEWIVPRGTL >vapB15839372 : c2866266-2866541, length 92, M. tuberculosis_CDC1551, VapB MRFSATDVYSIMLVAYICHVKRLQIYIDEDVDRALAVEARRRRTSKAALIREYVAEHLRQ PGPDPVDAFVGSFVGEADLSASVDDWYGKHE >vapB15839372 : c2866266-2866541, length 92, M. tuberculosis_CDC1551, VapB MRFSATDVYSIMLVAYICHVKRLQIYIDEDVDRALAVEARRRRTSKAALIREYVAEHLRQ PGPDPVDAFVGSFVGEADLSASVDDWYGKHE PGPDPVDAFVGSFVGEADLSASVDDWYGKHE >vapB|15839372 : c3131225-3131449, length 79, M. tuberculosis_CDC1551, VapB MTRKMTATEVKAKILSLLDEVAQGEEIEITKHGRTVARLVAATGPHALKGRFSGVAMAAV

DDDELFTTGVSWNVS >vapB15839372 : c3131225-3131449, length 79, M. tuberculosis_CDC1551, VapB MTRKMTATEVKAKILSLLDEVAQGEEIEITKHGRTVARLVAATGPHALKGRFSGVAMAAV DDDELFTTGVSWNVS DDDELFTTGVSMNVS >vapB|15607142 : 71575-71823, length 83, M. tuberculosis_H37Rv, VapB MNSAMATIQVRDLPEDVAETYRRRATAAGQSLQTYMRTKLIEGVRGRDKAEAIEILEQAL ASTASPGISRETIEASRRELRGG >gi|15607207|ref|NP_214579. 1| hypothetical protein Rv0065 [Mycobacterium tuberculosis H37Rv] H37Rv] PRLIEYTWQLRHNVTFYDALYVALATALDVPLLTGDSRLAAAPGLPCEIKLVR PRL, IEYTWQLRHNVTFYDALYVALATALDVPLLTGDSRLAAAPGLPCEIKLVR >gi|15607690|ref|NP_215064. 1| hypothetical protein Rv0550c [Mycobacterium tuberculo- sis H37Rv] MLSRRTKTIWCTLVCMARLNVYVPDELAERARARGLNVSALTQAAISAELENSATDAWLE GLEPRSTGARHDDVLGAID AARDEFEA >gi|15607689|ref|NP_215063. 1| hypothetical protein Rv0549c [Mycobacterium tuberculo- sis H37Rv] MRASPTSPPEQWVDASAMVDLLARTSDRCSAVRARLARTAMHAPAHFDAEVLSALGRMQR AGALTVAYVDAALEELRQV PVTRHGLSSLLAGAWSRRDTLRLTDALYVELAETAGLVLLTTDERLARAWPSAHAIG >gi|15607797|ref|NP_215171. 11 hypothetical protein Rv0657c [Mycobacterium tuberculo- sis H37Rv] MSVTQIDLDDEALADVMRIAAVHTKKEAVNLAMRDYVERFRRIEALARSRE >gi|15607796|ref|NP_215170. 11 hypothetical protein Rv0656c [Mycobacterium tuberculo- sis H37Rv] MAAATTTGTHRGLELRAAQRAVGSCEPQRAEFCRSARNADEFDQMSRMFGDVYPDVPVPK SVWRWIDSAQHRLARAGAVG ALSWDLLICDTAAARGLWLHDDADYELAERHLPDIRVRRWSADD >vapB|15607142 : 1073325-1073543, length 73, M. tuberculosis_H37Rv, VapB MKTLYLRNVPDDWERLERLAELAKTSVSAVAVRELTEASRRADNPALLGDLPDIGIDTT ELIGGIDAERAGR >gi|15608100|ref|NP_215475. 1| hypothetical protein Rv0960 [Mycobacterium tuberculosis H37Rv] H37Rv] MIWDASAALAALLNDGQARQLIAAERLHVPHLVDSEIASGLRRLAQRDRLGAADGRRAI, QTWRRLAVTRYPWGLFERI WEIRANLSAYDASYVALAEALNCALVTADLRLSDTGQAQCPITWPR >gi|15608859|ref|NP_216237. 1| hypothetical protein Rv1721c [Mycobacterium tuberculo- sis H37Rv] MVQIRNVPDELLHELKARAAAQRMSLSDFLLARLAEIAEEPALDDVLDRLAALPRRDLGA SAAELVDEARSE >gi|15608858|ref|NP_216236. 11 hypothetical protein Rv1720c [Mycobacterium tuberculo- sis H37Rv] MIVLDASAAVELMLTTPAGAAVARRLRGETVHAPAHFDVEVIGAIRQAWRQLISDHEGLV WVNFLSLPVRRWPLKPFT QRAYQLRSTHTVADGAYVALAEGLGVPLITCDGRLAQSHGHNAEIELVA >vapB|15607142 : c2506381-2506208, length 59, M. _tuberculosis_H37Rv, VapB MALWYQAMIAKFGEQWDAKVWAPAKRVGVHEAKTRLSELLRLVYGGQRLRLPAAASR >vapC|15607142 : c2506381-2506208, length 139, M. tuberculosis_H37Rv, VapC MT MACTACPTIWTLRCQTTCSNAFTGEALPHRHPRLAADAVNETRAIVQDVRNSILLSAA SAWEIAINYRLGKLPPPEPSASYVPDRMRRCGTSPLSVDHAHTAHRRASGSPSTSIRPCA HRPGTAAWPDDHHRRRPVSCL HRPGTAAWPDDHHRRRPVSCL >gi|15609682|ref|NP_217061. 1| hypothetical protein Rv2545 [Mycobacterium tuberculosis H37Rv] MSTTIVAGVIQGHLPVILPTRRRARDLGHTTALFRAQTLQCIYLSIEYLYVCSMSRRTTI DIDDILLARAQAALGTTGLK DRVDAALRAAVR >gi|15609683|ref|NP_217062. 11 hypothetical protein Rv2546 [Mycobacterium tuberculosis H37Rv]

MVFCVDTSAWHHAARPEVARRWLAALSADQIGICDHVRLEILYSANSATDYDALADELDG LARIPVGAETFTRACQVQRE LAHVAGLHHRSVKIADLVIAAAAELSGTIVNHYDENYDRVAAITGQPTENIVPRGTL ------------------------------------------------------------ ------- >gi|15609687|ref|NP_217066. 1| hypothetical protein Rv2550c [Mycobacterium tuberculo- sis H37Rv] MLVAYICHVKRLQIYIDEDVDRALAVEARRRRTSKAALIREYVAEHLRQPGPDPVDAFVG SFVGEADLSASVDDWYGKH E >gi|15609686|ref|NP_217065. 1| hypothetical protein Rv2549c [Mycobacterium tuberculo- sis H37Rv] MIFVDTSFWAALGNAGDARHGTAKRLWASKPPWMTSNHVLGETWTLLNRRCGHRAAVAAA AIRLSTWRVEHVTADLEE QAWEWLVRHDEREYSFVDATSFAVMRKKGIQNAYAFDGDFSAAGFVEVRPE ------------------------------------------------------------ -- 7 >gi|15609967|ref|NP_217346. 1| hypothetical protein Rv2830c [Mycobacterium tuberculo- sis H37Rv] MTATEVKAKILSLLDEVAQGEEIEITKHGRTVARLVAATGPHALKGRFSGVAMAAADDDE LFTTGVSWNVS >gi|15609966|ref|NP_217345. 1| hypothetical protein Rv2829c [Mycobacterium tuberculo- sis H37Rv] MTTVLLDSHVAYWWSAEPQRLSMAASQAIEHADELAVAAISWFELAWLAEQERIQLAIPV LSWLQQLAEHVRTVGITPSV AATAVALPSSFPGDPADRLIYATAIEHGWRLVTKDRRLRSHRHPRPVTVW ------------------------------------------------------------ ------- >vapB|15607142 : 3174744-3174989, length 82, M. _tuberculosis_H37Rv, VapB MLSDEEREAFRQQAAAQQMSLSNWLRQAGLRQLEAQRQRPLRTAQELREFFASRPDETGA EPDWQAHLQVMAESRRRGLPAP >gi|15610000|ref|NP_217379. 11 hypothetical protein Rv2863 [Mycobacterium tuberculosis H37Rv] H37Rv] VAHARTLHHRHPGLGARDLLHLACCQRRGVTRIKTFDHTLASAFRS VAHARTLHHRHPGLGARDLLHLACCQRRGVTRIKTFDHTLASAFRS >gi|15677515|ref|NP_274671. 1| hypothetical protein NMB1665 [Neisseria meningitidis MC58] MFQANIHQAKTNLSQLIQRAEAGEIVIIAKAGKPCVQLIGIEKPARNAGRLKKFSHMENT DISRILEDDNETAALFFEES AL >gi|15677514|ref|NP_274670. 1| hypothetical protein NMB1665 [Neisseria meningitidis MC58] MRKILLDTHALLWWLLDDKKLGISARKLIENPRNAIFVSAASIWEISIKQNKGLLKLPEE FFDVLQEEDFEMLPIGLFHA KQAGSLPEIHKDPFDRMLIAQTQAEGFELMTVDEYIPQYGIRWNASS >vapB|30248031 : c316448-316260, length 63, Nitrosomonas europaea, VapB MASTFRLSSLCCIARRTAAWRALPCNICPIIPPVSVANHTIHHHNAGPNNYLLIRRAWN SER >gi|30248306|ref|NP_840376. 1| PIN (PilT N terminus) domain [Nitrosomonas europaea ATCC 19718] MLILDSNTISYYFRGDPQWLRLQAQRPQDVAVPAIVEYELRYGLLRLPPEMAAPRLAALT TLLLPMQKLPFDSECADHA ARIRTTLEAAENPIGPHDTLIAATALRHGATLITRNVREFSRVPGLQWINWHEG ------------------------------------------------------------ ------- >vapB|30248031 : 1155550-1155774, length 75, Nitrosomonas_europaea, VapB MGHRRCGSGVPPLARTGTACGLHLMLLLDTNVISELLKVRAGKADPHVTTWGRTVPGASL YVSVITVQELEIGTL >gi|30249063|ref|NP_841133. 1| putative plasmid stability-like protein [Nitrosomonas europaea ATCC 19718] RISGLVP RISGLVP >gi|30249207|ref|NP_841277. 1| Hypothetical protein NE1225 [Nitrosomonas europaea ATCC 19718] MQVTDKGQVTIPKRLRDAAGFLPGSQVTFSLEGGKIIISKTGMGTDDRRKSLRAAAAKVR KSLDEPFKQMNSDDIMAFLR PDGDDCA >gi|30249208|ref|NP_841278. 11 Hypothetical protein NE1225 [Nitrosomonas europaea ATCC 19718] MATIVHDLSKYDGSAGFLVDTNIWIDCMDTDSRWHDWSVDQLQICSEQAPLHINLMIYTE LLIPGPDIDALDTMLDIYDT

LRSPLPWSCAGLAAKAYLNYRRRGGTRLVPLPDFYIGTHAAVANLSVLSRDVKPYHNYFR RLRCVGPDETAEQHTDG ------------------------------------------------------------ ------- >gi|30249559|ref|NP_841629. 1| Hypothetical protein NE1589 [Nitrosomonas europaea ATCC 19718] MTIQWNHYGSISIGKLRNAMPTTLTLKNIPDDVYERLKVAAEMHRRSLNSEIIVCLETVL MPTRISPGERLERARQLRAG LNSEKFQACDIDVMKRQGRP >gi|30249558|ref|NP_841628. 1| Hypothetical protein NE1589 [Nitrosomonas europaea ATCC 19718] MIWDSNVLAYFYLPGEYTAAAEALFEHDPDWVAPVLWRSEFRNILAGYLRRGSLTFLQAY NLQCEAEDLLAGAEYEVNS FSILELVRDSECSAHDCEFVALAIKLGAKLVTMDGKLLRMFPDIAFALSASQRSS >vapB|30248031 : 2296994-2297218, length 75, Nitrosomonas_europaea, VapB MKNIPDDVYERLKAAAEIHRRSLNSEIIVCLETVLMPTRISPSERLERARQLRAGLNPKK FQACDIAIMKRQGRP >gi|30250053|reflNP_842123. 1| Hypothetical protein NE2113 [Nitrosomonas europaea ATCC 19718] 19718] PSILELVRDSECSAHDCEFVALAMKLGAKLVTMDGKLLRAFPGIAFALSMS PSILELVRDSECSAHDCEFVALAMICLGAKLVTMDGKLLRAFPGIAFAISMS >gil7227644refJNP484192. l) unknown protein [Nostoc sp. PCC 7120] MTSQWDTTSDLIAKLETLPPEKLQQVLDFVEFLAQKYTQTPESEQTPQKRVLGLNQGEIW MSDDFNEPLPDEFWLGEGE I >gi|17227645} ref|NP_484193. 1| hypothetical protein [Nostoc sp. PCC 7120] MKLLLDTHVLIWSTGNPEKLSERVKNLLLDNNNSWIVSVASVWELQIKYQIGKLNLSSSL PNLIETQQRVNNLQILPIEL SHIYALDSLPNHHRDPFDRIVIAQAISEKIPLLSTDTVFDAYPVEKIW ------------------------------------------------------------ ------- >gi|17228249|ref|NP_484797. 1| unknown protein [Nostoc sp. PCC 7120] MKCIDAIAFGFWRVRSRYVSSDRLESSAKINNTVIRGKAMSNQELEQQLLSLDLAERIRI FQILAQSLTVQSSPPSPTPD AIDLKSDSEALLLSADRSPQHPLRKIPLTIPPDFDEPMPELWDALGQ >gi|17228248|ref|NP_484796. 11 hypothetical protein [Nostoc sp. PCC 7120] MILLDTHIWLWWLHSPEQLSESGRTLLTIGENQNALIVSAISVWEIAIKHSNGKLPLPLP INEWFALAKTRPGITIEPLD PLDAITSTQLPGDFHKDPADRIIVAIAYRRNIELMTCDQKVLNYPHIKTIC >gi17230178IrefNP_486726. 1 unknown protein [Nostoc sp. PCC 7120] MEHIATSELPETLQQIFAEIQRTKTPVTVTHDGEPLVIIYPATPQPQRPAFGAMKGSGEI LGDVIAPVIPAATWEALQ >gi17230177refINP_486725. 11 hypothetical protein [Nostoc sp. PCC 7120] MKLLLDTHIWLWYLLGNERLSPGLQTTIAATTTELWLSPISIWETLLLAEKGRISLQPNP VAWVDLALNTLEIREAPLNR HIAILSRQIQLPHQDPGDRFIAATAVHHQLTLATVDTNLTGTSWLQTLS >vapB|17227497 : c3788612-3788415, length 66, Nostoc_sp_PCC_7120, VapB MRDRFNLPQILIIKPYVKLVMLLIDTSVWISVFRNRSGQVRQQLETLVANRQNSLGSPSL NCCKW >gi|17230620|ref|NP_487168. 1| hypothetical protein [Nostoc sp. PCC 7120] MLQGSLNEQEWTLLSTYLEAQDYVELTPSSWREAARIYYDLRRQGLTVRSPIDCCIAQVT LENNLLLIHDDRDFETITQV RYLQHLRFQP RYLQHLRFQP >gi|17230960|ref|NP_487508. 1| hypothetical protein [Nostoc sp. PCC 7120] MYSLEIPEGQAEFAELLRRVRDGEEVIISQAGTPIARIVPIAEQKLPRIPGLDRGQVTIS PDFDAPLPDEVLNAFINPTD AEA >gi|17230961|ref|NP_487509. 1| hypothetical protein [Nostoc sp. PCC 7120] MRALLDTHTFIWWVIDDNRLSSTARNIIADPGNNLFFSAASAWEIVIKVRLGKLNLPEPP ETYIPNRLTINRFESLPIQM NHALQWNLPALHQDPFDRIIIAQSQVEKMPIITVDNKITQYPVDVIW NHAI, QWNLPALHQDPFDRIIIAQSQVEKMPIITVDNKITQYPVDVIW >gi|17231465|ref|NP_488013. 11 unknown protein [Nostoc sp. PCC 7120] MLKSYEAIYENGQIKWISEQPQVNTARVIVTFIEETLPSKKRRTAPESIAGKGKTLGDIV SPIVDEEDWECLK >gi|17231464|ref|NP_488012. 11 hypothetical protein [Nostoc sp. PCC 7120] MSEVIVLDTHIWFWLINQEFQRFPTQWREAIETAEQVGISVISCYEIALAQQRGRLQLPC AANQWFQEALQPADITLFPL TPEIVCRAVDLSPIHKDPFDRLIVATTLEYQAKLASVDSLFSQYPELDTHLMK

------------------------------------------------------------ ------- >gi|17231628|ref|NP_488176. 1| unknown protein [Nostoc sp. PCC 7120] MHQINLKEAETRLAELIEEVASGQEVIITRSDGASFKIVPIGEVKAYPKFGSAKGLVKIS DDFDEPLADFEEYAP >gi|17231627|ref|NP_488175. 1| hypothetical protein [Nostoc sp. PCC 7120] MRLMLDTHTFLWFIEGSLNLSDTAKSLIEDQQNQRFLSIASLWEISIKVSIGKLELDMTF TELVKQQVYGNAIELLEIQP AHLDELAKLPFYHKDPFDRLMISQSLVESIPIVTKDSVFEGYPVQILW ------------------------------------------------------------ ------- >gi|17232092|ref|NP_488640. 1| unknown protein [Nostoc sp. PCC 7120] MIFKEMNMTQVILKQLNPIVLEKLKRLAQSHQRTLEEEITSILEDVAEKEEEPKSSEGFW DMTLQFRERMQQENITFDDA DFADIRDRSVGRDVEF >gi|17232092|ref|NP_488640. 1| unknown protein [Nostoc sp. PCC 7120] MIFKEMNMTQVILKQLNPIVLEKLKRLAQSHQRTLEEEITSILEDVAEKEEEPKSSEGFW DMTLQFRERMQQENITFDDA DFADIRDRSVGRDVEF DFADIRDRSVGRDVEF >gil7232625] refNP489173. 1 unknown protein [Nostoc sp. PCC 7120] MRWRSYNKWYHYLVAINSMEREALTIRFPSELLTKARKLKGSNESFNDLWEALESEVKRR RGWAAHQRILARSETIKAK TGIQPSSTEMIRSLREGEGRRD >gi|17232624|ref|NP_489172. 11 hypothetical protein [Nostoc sp. PCC 7120] MREDVTRVLCLDTSVWIPYLVPEVYQSQAVTLVTEALSLNIRLVAPAFAWAEVGSVLRKK TRMGVITAEEALGFFEDFCE LPIDYIEEEAIRLRSWEIAEQYGLLTLYDAAFLACAEMTSAEFWTADAALVKQVIPRPSY LREIGEI ------------------------------------------------------------ ------- >gi|18311711|ref|NP_558378. 1| Hypothetical protein PAE0101 [Pyrobaculum aerophilum str. IM2] MEIVEVDGFGRIYLPAEIRKRIGARRFRVKIVDNGILLEPVDDVDKYYGSYGPPRYKSLE DIEEAIRDVSQVDLR >gi|18311712|ref|NP_558379. 1| Hypothetical protein PAE0101 [Pyrobaculum aerophilum str. IM2] MYRKWIYVDVNVLYYFFTAHPEYGEGSRELIKKYAGRLATSALTAWLLYVLTRNEGIVEA TRDLTTLLPLDVEVLNKAKR LNKPRDFEDRIHLATMQIYGIDTILSNDGDFDEAGVQRIAPRRKGE >gi|18311748|ref|NP_558415. 11 Hypothetical protein PAE0151 [Pyrobaculum aerophilum str. IM2] MSEVISIRVRRGLKKELEELGINYAEAVRKFLEELVARERRRRALERARALREELRKKGA FPPSAELIREDRDEASR >gi|18311747|ref|NP_558414. 1| Hypothetical protein PAE0151 [Pyrobaculum aerophilum str. IM2] MKLWDASAIAALYVPEERSEQAERAVSQAQELHTLDLAAYEVANDLWKHARRGLLREDEA SNMLEELWEFFKALKVHSY AEVLKDAFALALKHGVTVYDAAYVALAEKIGGKLLTLDRQLAEKFPALVTP -------------------------------------------------- 7---------------- >gi|18311873|ref|NP_558540. 1| Hypothetical protein PAE0337 [Pyrobaculum aerophilum str. IM2] MKKLTLSVREETLRRVRAVLSRAGLKTSISELFDDYIALMDGEGLAAELCSELKLDCGGQ FYTPDEVKAKRPAALGPPAS ELVKELRRARESRL >gi|18311874|ref|NP_558541. 1 Hypothetical protein PAE0337 [Pyrobaculum aerophilum str. IM2] MIYLDTSALIKRYVKEADSDWDGLFEAAYRGEVAVSTSVFNIGEAATAADKKARRGELSG DVRTAVSLMLREIAVLSSL GSLVIVPIGLSVMKASIHIALTHKLYIADALQIASCLRVKCHELYTADKALADAAEKEGI KTRVLR ------------------------------------------------------------ ------- >vapB|18311643 : 335372-335986, length 204, Pyrobaculum aerophilum, VapB MLGGDGTLLEAIRRHPCVLESWIHLGLGKVNFYKSAEITLPIDEAVSRVLKGEYKVLEL STLESDGCIALNEAAVYRRDPGRLLSFKITTDEGQIAGRADGIIVSTPHGASGYWSTFG PWDYRADVIWSFVAPYTLYLRPMVLTSKRWIETREDAVLVCDGREARMGRVFEVAKG QRRLKLAIFGDFQFIQRVAERLRSL >gi|18312054|ref|NP_558721. 11 Hypothetical protein PAE0624 [Pyrobaculum aerophilum str. IM2] MKCYALDASAFFHGRDARLFSGQLYTTKNWEELKDPRAQALLEVWRVEIVEVDEKKVREL LKKYGGLSPADASVLILAL ERGCVLITDDGRLASIAKKLGVEVLGIFYKR ERGCVLITDDGRLASIAKKLGVEVLGIFYKR >gi|18313566|ref|NP_560233. 11 Hypothetical protein PAE2754 [Pyrobaculum aerophilum str. IM2] MSVIISVRVRRELKEKAKRLGIDIRRWERALEEEIKRREEEELAKSLEELRRALSGISER EWVEAVREARNAR

>gi|18313565|ref|NP_560232. 1| Hypothetical protein PAE2754 [Pyrobaculum aerophilum str. IM2] MPVEYLVDASALYALAAHYDKWIKHREKLAILHLTIYEAGNALWKEARLGRVDWAAASRH LKKVLSSFKVLEDPPLDEVL RVAVERGLTFYDASYAYVAESSGLVLVTQDRELLAKTKGAIDVETLLVRLAAQ ------------------------------------------------------------ ------- >vapB18311643 : 2133278-2133844, length 189, Pyrobaculum-aerophilum, VapB MREAERALLELRVGLKDKFYLISGRRLAAWKYTYETHVDLMPLTSVGAEGQFTPHHLSRI LTMSSYEAVRDALYNYLEIADIEDVRVGLVKTGRIALYVKKGGLWTNGYNAGNYTKAVLP VLLQMLLANEGSSVFIDDVDLAVPSGRAEVLLSALFEIARKRNLQLVASAKEPGFAEIAE KLGFTIAKL >gi|18314154|ref|NP_560821. 11 Hypothetical protein PAE3561 [Pyrobaculum aerophilum str. IM2] MLDTSALLYIVEHRLDIWELSEHEIYIPSAVLEELNALSRRSRKARVALQLLSLLKYKWE RGGPADKAVLETAVEEGAV LITGDTALAEEARRRGVPVAKFHKGQLAIY LITGDTALAEEARRRGVPVAKFHKGQLAIY >vapB|14518450 : c447806-448138, length 111, Pyrococcus_abyssi, VapB MNLALWSAWSDKNVLVPQHGSWSDGLHSWKWKTNPDGNVELSGMTFRWNAEWNYSGGPE NIDLSGKGRFSPKIPIPLYIEGRFYSKDPETGEEVEVYGEYELEDMKLEEI >gi|33356691|ref|NP_126156. 2| hypothetical protein PAB2041 [Pyrococcus abyssi GE5] MRTFLFPPSLSFIMKGKVWLWPDTNFLFIPGQFGVDIISEFERILDVKYQVAIPNWLEEI KTIIREGKVKGKDLMAAK IALKIAERFPKIYVGEFLSKPTDELLYEYAIANDNVIICTNDRKLRKRLREAGVPVIFLR QKKKLELEGILE ------------------------------------------------------------ ------- >vapBI14518450 : 761684-761887, length 68, Pyrococcus_abyssi, VapB MWLEALFLYGENMEVIKVEIPRELEEDVKRYIKLLKKRREVLKKTFGILKTEKTAKELKV EIYDELYD >gi|14521013|ref|NP_126488. 1| hypothetical protein PAB0550 [Pyrococcus abyssi GE5] MTSFMIDSTLIIEHLKGNPIARKILEVLIDSDVNVYINDVVASEVIFIYLKLTTGKSYLT LKKNPVIVRSVDKTSVYELL GMFKFLETNEFVFSIAKRLIDKYGLLPNDALILATAIFYRCDYLIALDSDYKEPCEAEKI RLISTKEELEKALHNH ------------------------------------------------------------ ------- >vapBI14518450 : 834293-834433, length 43, Pyrococcus_abyssi, VapB MVIYLDANVIVGYLIYTDKTEEIKELLEKDEIFVTTINTLFWDEINL >gi|14521081|ref|NP 126556. 1| hypothetical protein PAB7218 [Pyrococcus abyssi GE5] MRLIFEEHYGEYKLKKLKKSLSQKFEIYRAYLRNLNRLIWIPAPSDVSKLTYIMEKYSLL PNDALIVLTCKVYGINKIA TFDSDFENVDFLEKLP TFDSDFENVDFLEKLP >vapB|14518450 : c898293-898093, length 67, Pyrococcus_abyssi, VapB MKTIAVDEETWEAIKRLKAKLDAKSYTEVLKKLIEVWHSVELEMKAEKVTIEDDKAEMII SLLENSE >gi|14521141|ref|NP_126616. 11 hypothetical protein PAB1741 [Pyrococcus abyssi GE5] MRMLPERISFGPISFLKITRKQNKEILEFILAEFQVFLPLPAVNSYLMTKGLLGRDIDEE IKILREVFTIVEVSDQLIRK MAELGGALVKEGIVPNFSDLITAASAIITESLLWNDKKVKDYEIFSKYGLDVISYTKFLE EIESLAEEEAKRVAK >vapB|14518450 : cl009921-1009637, length 95, Pyrococcus_abyssi, VapB MYQYVHYMQIYGDINMNVEVKRIDSQGRIVLPKEWRKKWGSEVILIELDDRIEILPRKKP KLSEFFDIIEVEDIGEDIEKDLLKELGEDINEVHR >gi|14521256|ref|NP_126731. 1| hypothetical protein PAB1672 [Pyrococcus abyssi GE5] MGRILMRFIDSNIFLYAMIKPKGNISKMILERKERSKRILLRVENGEDWTTWHLSEVANI LEAKVSLTTAIKFLESLF LAENVKILPVSAEDYLKAILLSKEKRISVNDALAYLKMKELGIKEIYTFDRHFYNLDVKW QE ------------------------------------------------------------ ------- >vapB14518450 : c1120616-1120338, length 93, Pyrococcus_abyssi, VapB MVIRMVTTKKVKIVQTEVDLGTYHTLRAIAVHRGVPLKEVIREILRNYAETYKRELIKEI HEDPIWKGIGLLNTGDPRASEKDDWGWKWSSE >gi|14521371|ref|NP_126847. 1| hypothetical protein PAB1599 [Pyrococcus abyssi GE5] MVKRMKSKLVYIDTGALIAFFDKRDKNHKIAVSYFESAILNGVRFWGRPVLMEFINGASK VNGKRVAIQLKNLIYSSRY ILIENETERDWEKAWEIFEKFDDQDGMDLVDCLSFAIMERLGIKKAFTFDSDFETYGFIW PRSQSNY ------------------------------------------------------------ ------- >vapB|14518450 : 1136739-1136951, length 71, Pyrococcus_abyssi, VapB MRKVKNVGKWITLNVPDGMEDWKSLLEREARVIMRRLSRADFKSTFGILKGKRKSVDE

IEADIYDEWEV >gi|14521385|ref|NP_126861. 11 hypothetical protein PAB0789 [Pyrococcus abyssi GE5] MKLRLIFMTSGKFRFFIDSNVILNYFYGDDNAREIIEIAENAGEVFINGIVLTEVSIRYL KDETGEKSYTLKRKPELVKN VDKSPPYAVLGKFLYLSDNVLIGEDAVILMDIYGLLPNDAIILATCKFYGIKYLMSFDSD FREACKGEGIILIESKEKLD EIIKFGDSK EIIKFGDSK >vapBI14518450 : cll53817-1153542, length 92, Pyrococcus_abyssi, VapB MASLINFRNLKSHWMIVTFGGHMSKVITIEVPEWVDEERLKTILNKVLMELSPKVMPVDK LREMLGWELEEEITDHTYVREKEKERIKWLY >gi|14521399|ref|NP_126875. 1| hypothetical protein PAB1585 [Pyrococcus abyssi GE5] MVVLDTSIVIDRVKRKDEIKENITGITFVEYPAIIRYKKFHGNVLFPTFEDFLLAHKIQE RLLKIGKPKAFADLLIASIC ISNNEELITKDKDFLDIARVSNLRVKVIDV ISNNEELITKDKDFLDIARVSNLRVKVIDV >vapB|14518450 : 1260427-1260705, length 93, Pyrococcus_abyssi, VapB MVTSWSIRLKVGPKGQIVIPKVFREAYGIKEGGEVIIEPTDKGLVIKAPLDVKTLMEKL KERRKNMKGVGIQAKLGDLKDVDLEDEFNEDIP >gi|14521500|ref|NP_126976. 11 hypothetical protein PAB0859 [Pyrococcus abyssi GE5] MKIFLDASFIIYLNVDVPDSLAEKIDALYEQLITSSKLYTDVLVIDEVIHVSRKKYKVPY SKTIEMLDDIVIPYVEVLPI GLMEYLKAKENILKYNLKPSDAIHLAVIENNGIQAIVTEDEDFDRVPIKRIWL ------------------------------------------------------------ ------- >vapB|14518450 : 1291316-1291903, length 196, Pyrococcus_abyssi, VapB MHANEILDGKDLPLLYVGISPCFRKEAGTAGKDTKGIFRVHQFHKVEQFVYSRPEESWEW HERIIRNAEELFQKLEIPYRWNICTGDLGYVAAKKYDIEAWMPGQGRFREWSASNCTD WQARRLNIRFRDRTDEKPRYVHTLNSTAIATSRAIVAILENHQEEDGTVKIPKVLWKYTG FKEIVPVEKKERCCSS >gi|14521536|ref|NP_127012. 1| hypothetìcal protein PAB0881 [Pyrococcus abyssi GE5] MLLKLKLVLDSSVFIQGLDIEGYTTPKWDEVKDRESRILLESLISSGKVKWEPSKEALRA VKNAALKTGEIEELSEAD LEVLALAYELKAEVFSDDYNVQNVARILGLKFRTLKRGIKKVIKWQYVCIGCGRKFKEMP PGGICPDCGSPVKLIPRRQR S S >vapB|14518450 : 1501612-1501827, length 72, Pyrococcus_abyssi, VapB MKTIAVDESTWKKIKMLKDKLEAKSYDEVLQKLIETWHLVELDKKVDKVVKEEEAETLL SVLNKIKKKGES >gi|14521742|ref|NP 127218. 1| hypothetical protein PAB1341 [Pyrococcus abyssi GE5] MPLPPDITFDSVTLLKMHSEKNKRLLEITLAKFTVYLSMLTVQRYLTARAYLKRNVELEF EVLKDIYNIVPVSEEIILRA SKIEANLIRKGVFLDLEDIITAVTAIETGSLLITDEPKKYEPIRRFGLDTMPLDKFLREV ELMVEKEII ------------------------------------------------------------ ------- >vapB|14518450 : cl699062-1698781, length 94, Pyrococcus_abyssi, VapB MILLVSIRLKVGPKGQIVIPKVFREAYGIKEGGEWLEPTDKGLIIRAPIRVDDLIKKIR EERKKMNPKRRPKPGELRGISLEDEYEEEWRSEE >gi|14521921|ref|NP_127398. 11 hypothetical protein PAB1216 [Pyrococcus abyssi GE5] MKLFLDTNILVYLALGSVDPSYETSIDEFYRDLMKGHELYTDVLVLDEFIYILKRKYGVP YEKAITFIEETVIPWKILP ITFLDYLTAKDVMLKYKLKPSDAFHVAVIQNNGLQAIVSEDEDFDRLPLKRLWLRD >gi|33359474|ref|NP_877887. 11 Hypothetical protein PF0356 [Pyrococcus furiosus DSM 3638] MKTIAVDETTWKKIKMLKDKMEARSYDEVLQRLIETWHLVELDKKVDRIILNDEEAETLI SMLKKKKGS >gi|33359473|ref|NP_578084. 2| Hypothetical protein PF0354 [Pyrococcus furiosus DSM 3638] 3638] KPPDITFDSLALIRKGHSQSMKKILEITTAKFTVNLSIVTVYRYLTVRAYLKLDTIELEL DVLKDIYNIVPLNEEIAI KAAQIEADLMRKGMMPDIEDVLTAATAIYTKSLLITDDSKRYEPMRRFGLDTMPLDKFVK EVELMVEKELI >gi|18977146|ref|NP_578503. 1| Hypothetical protein PF0774 [Pyrococcus furiosus DSM 3638] MFGEIVPRPTMLKYDARIQCIGEVMVKTITVSDDVYNELLRIKGKKSFSELLRELLREKK GNSVALKHIYGILNGEEYRE TRKRLKELEKEFEKWKQFLTQV >gi|18977145|ref|NP_578502. 1| Hypothetical protein PF0774 [Pyrococcus furiosus DSM 3638] MEAVLDTSVIIEIARGNREILEKALGLDNTL

------------------------------------------------------------ ------- >vapB18976372 : 768291-768446, length 52, Pyrococcus_furiosus, VapB MKGDEWVIEEEGKVEILPRDVDLSKYVDSVEVDVDNFGDYHELRKELREKK >gi1189771531refINP-578510-11 Hypothetical protein PF0781 [Pyrococcus furiosus DSM 3638] 3638] IVEEVSDRDYMESVLLAEEKGVSINDALAYILMKRKGIEEIYTFDRHFENLDVRIVNS IVEEVSDRDYMESVLLAEEKGVSINDALAYII, MKRIZGIEEIYTFDRHFENLDVRIVNS >gi|18977147|ref|NP_578504. ll Hypothetical protein PF0775 [Pyrococcus furiosus DSM 3638] MIYLFLQNSVALNVGIGYIKIVLQIYLQVNYVGDGISIRVPPEIKHEMEKLKGEVNWSEE IREFIKRKIKEYKMRKALQE VIAYIQALPEAPRGTAQKLVGKDRDNH >gi|18977147|ref|NP_578504. 1| Hypothetical protein PF0775 [Pyrococcus furiosus DSM 3638] MIYLFLQNSVALNVGIGYIKIVLQIYLQVNYVGDGISIRVPPEIKHEMEKLKGEVNWSEE IREFIKRKIKEYKMRKALQE VIAYIQALPEAPRGTAQKLVGKDRDNH VIAYIQALPEAPRGTAQKLVGKDRDNH >vapBl18976372 : 1146253-1146840, length 196, Pyrococcus_furiosus, VapB MHANEILDGKDLPLLYVAFSPCFRKEAGTAGKDTKGIFRVHQFHKVEQFVYSRPEESWEW HERLVRNAEELFQELEIPYRWNICTGDLGYVAAKKYDIEAWMPGQGRFREWSASNCTD WQARRLNIRFRDRTDEKPRYVHTLNSTAIATSRAIVAILENHQQEDGTVKIPRALWKYTG FKEIVPVEKKEGCCKA >gi|18977577|ref|NP_578934. 1| Hypothetical protein PF1204 [Pyrococcus furiosus DSM 3638] 3638] MKLVLDSSVFIQGVEVEGYTTPSWEEIKDRESKLFLESLISAGKVRVIEPSKEAIEKIIQ AARETGELEELSKADIEVL AI., AYELKATIFTDDYNVQNIASLLGLKFRTLKKGITRVMKWRYVCIGCGRKFSTLPPGGICP DCGSRVKLIPRRR >gi|18977725|ref|NP_579082. 1| Hypothetical protein PF1352 [Pyrococcus furiosus DSM 3638] MEWSFRIPRELKKEMKKIDINWSEEVRKFIEEKVKEYKRKKALEEIDAMLANLPKAEKGT ARKYVREDRDSN >giII89777241ref] NE-579081. 11 Hypothetical protein PF1352 [Pyrococcus furiosus DSM 3638] MIVIDASSIAKYILREENWEKVRKYLLDKPYSLTLALAEVSNAIWKHYVLYKAISIEEAK LMYEALKRLEEDVITFEPLE NYLWDAMNIAISWGIPIYDALYLAQAKKYGKLLTSDKEQWKIAKKLGIKVEYVE >vapB|18976372 : cl596552-1596223, length 110, Pyrococcus_furiosus, VapB MTKGDLMAGNWGKPGKLPPVWTDLRLEVHLLERWGTEQELNVEPIKRKEVLLLNVGTA RTMGLVTALGKDEIELKLQIPVCAEPGERVAISRQIGSRWRLIGYGIIKE >gi|18978088|ref|NP_579445. 1| Hypothetical protein PF1716 [Pyrococcus furiosus DSM 3638] 3638] GDFMSKTTDELIYEFAISNDNVIVCTNDKQLRKRLREAGVPWFLRQKKKLELEGMLG . GDFMSICTTDELTYEFAISNDNVIVCTNDKQLRKRLREAGVPWFLRQKKICLELEGMLG >vapB|18976372 : cl897570-1897358, length 71, Pyrococcus_furiosus, VapB MIRSLRRLTMNHFELFVDSSVLVGLNLGDEKAKALVKSLIERGLTLVQSFSLKRLIRLCL PGPSRWIEGCL >gi|18978429|ref|NP_579786. 11 Hypothetical protein PF2057 [Pyrococcus furiosus DSM 3638] 3638] MKGVYDLKKHLNRYSNVYGKVKESIEQLMKNELLRIVEVNWEILKLSAEIGKNTLF >gi|33359257|ref|NP_877735. 1) hypothetical protein PH0098 [Pyrococcus horikoshii OT3] MGKIKTSIYIDADLWWELKKEAAEENRDISRLLEEIISENLLLDLEKNIEEMLKKFEKKI EFEPLPSRGSVSELVRRIRD EREGNILR >gi|33359258|ref|NP_142113. 2| hypothetical protein PH0098 [Pyrococcus horikoshii OT3] MSEKVIYLDSSAIIKRYIREENSDRMVELYTQAYQGDIKLAFSLWNIGEVLGAFDRAKRI KRIDVETYELARLRFLSEIL RMKRLGILKIIPLYSSILIGSWELLEKYHIYQADAIQIESARRVNASEFYTADKRLHQVA LSEDLNSFLI >vapB|14589963 : c351629-351390, length 20, Pyrococcus_horikoshii, VapB MVIKWCMEVISFRIPSELKKEMKKIDINWSEEIRKFIEAKVREYKRKKALEEIDAMLEN

LPRTEKGTARKYVREDRDSN >gi|14590297|ref|NP_142363. 1| hypothetical protein PH0389 [Pyrococcus horikoshii OT3] MIVIDASSIAKYILREENWEEVRKYLLDDPHSLTLALAEVSNAIWKHYVLYKWSAEEVGI MLKALKRLEEDVINFEPFE HYLKDAMSIAINWSIPVYDALYLAQAKRYGKLLTSDKEQWRIAKKLKIKAEYVE ------------------------------------------------------------ ------- >vapB|14589963 : c372554-372781, length 76, Pyrococcus-horikoshii, vapB MFGVGCLSKWTIRVPEWVDEEKLREIINMALAEISPRIMSINKLREILGVEEVEEEISD DVYVREKEKERVKWLY >gi|33359290|ref|NP_877761. 1| hypothetical protein PHS014. 5n [Pyrococcus horikoshii OT3] MTFVKYPAIVRYKKFYGNVLFPTVEDFLLAHKIQEELLKMGKPKTFADLLIASICINNGE ELITKDKDFSDIAEVSNLKV KIVEE KIVEE >vapB|14589963 : c452910-452704, length 69, Pyrococcus_horikoshii, VapB MKTIAVDETTWKKIKMLKDKMEARSYDEVLQKLIETWHLVELDKKVDKVMVNDEEMKILM SILKKKKGS >gi|14590406|ref|NP_142472. 1| hypothetical protein PH0499 [Pyrococcus horikoshii OT3] MPLPPDITFDSLALIKMHSQNMKRILEVTLAKFTVNLSIVTVYRYLTARAYLKKNIEAEF EILKDIYNIVPLLDDIAIKA AQIEANLIKKEITLDMEDIITATTAIYTNSLLVTDDPKRYEPIRRFGLDTMPLDKFIKEV ELMVEKELI ------------------------------------------------------------ ------- >vapB|14589963 : 631040-631294, length 85, Pyrococcus_horikoshii, VapB MKTIAVDEETWEAIKKLKARLDAKSYDEVLKKLIQAWHTLELETKAESISLDDEEAELVL SVIKERGRFVQEGNKNDSNASKNLL >gi|14590586|ref|NP_142654. 11 hypothetical protein PH0709 [Pyrococcus horikoshii OT3] MTPMLRKICFDPSSFIQLTRKQNKELLEFVLAEFEIYLPITTVHAYLLAKSFKGKDPKKE VQKLRGIVRIVDLTDDLLGE IAEIDASLIKDGYFLSLEDLITAVSAIASKSLLWSGNAEKYSPLRKYGLDCVNYDKFLEE VEVLAREEAKREKLI ------------------------------------------------------------ ------- >vapB|14589963 : c632499-632206, length 98, Pyrococcus_horikoshii, VapB MEAWMPGQGKFREWSASNCTDWQARRLNIRFRDRTDEKPRYVHTLNSTAIATSRAIVAI LENHQEEDGTVRIPKVLWKYTGFKEIVPVEKKERCCAT >gi|14590587|ref|NP_142655. 11 hypothetical protein PH0710 [Pyrococcus horikoshii OT3] MLRNLKKTLVLDSSVFIQGIDIEGYTTPSWEEIKDRESKIFLESLISAGKVKIAEPSKES IDRIIQVAKETGEVNELSK ADIEVLALAYELKGEIFSDDYNVQNIASLLGLRFRTLKRGIKKVIKWRYVCIGCGRKFST LPPGGVCPDCGSKVKLIPRK R R >gi|14590763|ref|NP_142833. 1] hypothetical protein PHS027. 1n [Pyrococcus horikoshii OT3] MPITKVTRNYRITIPAEIRKALGIKEGELLEVKLEDGKIIIERLKKERKTLKLGKKLTPE EIEKAIVEGMKECI >gi] 3335934l) ref) NP877801. 1 hypothetical protein PHS027. 1n [Pyrococcus horikoshii OT3] MHIVLIYDTFIDSEFHKKARSLLDSLDRWYIPPTVLQEYVWFFRSQGFSSRDAKIMLSEY IRSKLTFSKGKTSLCHSLMI >vapB|14589963 : c821653-821345, length 103, Pyrococcus_horikoshii, VapB MAGLGVAVALKMSSMEGFQIIVMMLMLPMMFLSGAFYPVRTMPNWMQWLAKINPLTYAVD GARYYLAGVTPTFGIMQDWIVLILLALVFAGFAGLEFRKAYLS >gi|14590765|ref|NP_142835. 1| hypothetical protein PH0911 [Pyrococcus horikoshii OT3] MIFVYFSLRDEKAKALVKSLIERSFTLVINPWF'SETAYKVMFTLALRDGLKGVYDLRKH LDRYAWVYGKVKKSIELLIK NELLRIVEVNAEIGEKYALLTNDAIIVATCKYYEIQKIATFDEDFKKVDFIEIIDSSL ------------------------------------------------------------ ------- >vapB|14589963 : c1168172-1168014, length 53, Pyrococcus_horikoshii, VapB MRVQKTLAPGLIWNIHPLINKPTHITPDFSGLSLPRKPILHHSTPLYNKRRGK >gi|14591108|ref|NP_143183. 11 hypothetical protein PH1298 [Pyrococcus horikoshii OT3] MSKYRGFLQRKKDLEKSLRELRLEWEGFLINTNILIYYLADAIPEDEIPRIEKILKEDFN ISIITKIEFLGRKGHTSEGF EKSREFISFARVIPLTDDIAELAIELRRRKSIKLPML >vapB|14589963 : 1501435-1501986, length 184, Pyrococcus_horikoshii, VapB MYPWDIGWSGIFSPMGGEERFVGVEFEYRGKKFTVINPTPYKKGLFPYINGNSEWMKELN

DDLNNLYMGWAAMVNLALWSAWSDKNVLVPQQGTWSDGTHSWEWETRPDGEITFSGVTFR VINAEWKYSGEPEGIKLSGNGKFAPEIFIPLSVEGWFSSKDPKTGENIEIYGAYELQDIK LEEI >gi|14591473|ref|NP_143553. 1| hypothetical protein PH1710 [Pyrococcus horikoshii OT3] MRKVNLVIPDTNFLFIPGQFGVDIISELSRILDVKYQIAIPNVVIDEINTIIREGKVKGR DLLAARIALKIAERFPKIYI GEFLSKSTDELLYEYAITHDNVIICTNDRTLRKRLREAGVPVIFLRQKKKLEIEGMLD ------------------------------------------------------------ ------- >vapB|14589963 : 965798-965962, length 55, Pyrococcus_horikoshii, VapB MYFVHTCTYEVTSMSKTITIADDVYYELVKMKGKRSFSEVLRELIGKKKEGISTY >gi|14591761|ref|NP_142973. 11 Predicted nucleic acid-binding protein, contains PIN domain [Pyrococcus horikoshii OT3] MDTSIVIEIFKGNRKILDQLSPTEEYSLPSIVLFELLCGNLKPRQRLALEKLPIVDFDRV SAEVASEIFKDLASKGQRPP TRDLLIAATAIAYNMHLLTCDKDFERFKDYV TRDLLIAATAIAYNMHLLTCDKDFERFKDYV >gi|15964819|ref|NP_385172. 1| HYPOTHETICAL PROTEIN SMc02658 [Sinorhizobium meliloti 1021] MATTVTIKGQVAIPKAVRELLGIKPGSKVDFRRTGSGIVEIRRADSKPVRSRFQNLRGHA GEGLSTDDIMALTRGDA >gi|15964820|ref|NP_385173. 1| HYPOTHETICAL PROTEIN SMc02657 [Sinorhizobium meliloti 1021] MTLVDTNVLLDLVTDDASWAGWSIDQLKAASLQGPLLINDVIYAELGVRYERIETLDSFI AEAGLELLALPRAALFLAGK VFVPFRARIQAHCL VFVPFRARIQAHCL >vapB|15896971 : 360012-360608, length 199, Sulfolobus_solfataricus, VapB MIRSFDVNKPGTQFNELKGGVIGGSIIQGLFKVDQEIKVLPGLRVEKQGKVSYEPIFTKI SSIRFGDEEFKEAKPGGLVAIGTYLDPSLTKADNLLGSIITLADAEVPVLWNIRIKYNLL ERWGAKEMLKVDPIRAKETLMLSVGSSTTLGIVTSVKKDEIEVELRRPVAVWSNNIRTV ISRQIAGRWRMIGWGLVEI >gi|15897346|ref|NP_341951. 1| hypothetical protein SS00412 [Sulfolobus solfataricus P2] MENDRMGFSRDLKVLVDTNILLYVYDGLDPFNKVLEFLDYKPSFFIHSTVLRELDILFEK NKKGFIISSRIKIARKYLEV MENDRMGFSRDLKVLVDTNILLYVYDr. LDPFNKVLEFLDYKPSFFIHSTVLRELDILFEKNKKGFIISSRIKIARKYLEV YKNLWNLINDYDDLPTDEALIRTALKHNMFIFTNDKELKNDAIKKGIGVLFLQNRSKIIK SLYPI >vapB|15896971 : c683385-683083, length 101, Sulfolobus_solfataricus, VapB MKEVKTHYFVTLNPPRSITALQPITVSVGALSAIGILAYLLSRLDKGEDNIREWEKALD EAIKEKEKERLRETALKIKELMKDVNEEEWATVIRENRNER >gi|15897701|ref|NP_342306. 1| hypothetical protein SS00799 [Sulfolobus solfataricus P2] P2] MKSALYPKGLDYIDKIDVKKIYSLTLTFYEVGNNKEYYIHKKVKDPITLSMLFNDLLRRF NVKGV MKVAIDKGLTYYDASYVYVAESLGLTLVSNNRELIRKANAITLEELIKGV >vapB|15896971 : c725687-725481, length 69, Sulfolobus_solfataricus, VapB MSERIKEKIYDTNALIKIHKNKSLLSTTNYVTTSILNVIEYPPIIDLKEKLIIIYPTRSD YELAIKDNG >gi] 15897743refNP342348. 1 hypothetical protein SS06663 [Sulfolobus solfataricus P2] P2] MVKLRRIGEPVNAVDIILSSIALNRDMIIVTNDNDFESIKKVEERLIZIEKMR >vapB|15896971 : 1073660-1073923, length 88, Sulfolobus_solfataricus, VapB MYENFIYVYLVYIYMSDVISVRVKKELKKKAEELGINVREWEKALEEAIREKEKEELKD MTMKIKELMRDVSEYDWVSTVRESRDER >gi|15898090|ref|NP_342695. 11 hypothetical protein SS01243 [Sulfolobus solfataricus P2] MKDKEFLLDASALYSLLDYVDKVDVKKIHVLTLTFYEVGNVIWKEYYIHKKVKDPITLSR LFYKLMRKFNVIEDSPLEGV MRIAIERGLTYYNASYAYVAESLGLILVSNDKELIRKANAISLKDLIKSM MRIAIERGLTYYNASYAYVAESLGLILVSNDKELIRKANAISLKDLIKSM >vapB|15896971 : 1340360-1340617, length 86, Sulfolobus_solfataricus, VapB MYYLHLKFTMERMISKVTRNFQVTIPYEIRKVLGIKEGDYIEFAIENGKVMIKPVRKVWS TIRLGREVTVEEIEEIASKAFKDDSS

>gi15898313refNP_342918. 1 hypothetical protein SS01483 [Sulfolobus solfataricus P2] MEEKLQWRRLRKSQVRPLKMIWDTNVLIYATLEDSEFHTQSLEIIEGSDIIVPQIWFEYI KVLSEIVQNLDFIKTKIS ELNNFVVVCEDLNTIALALRLLAELKLSLKDINDMIILTAAIKTNSSIATFDQKLRKIAD KKGVKVLP >gi|15898324|ref|NP_342929. 11 hypothetical protein SS01494 [Sulfolobus solfataricus P2] MVIKNATILIYVPEIETFIFPVYVYYNMKTVYSLRLDKELREEMEKYNVKWNEEIESFIR KRIEELKKEEILKKINEILQ TMPETKSNSADLVREDRDNN >gi15898323) refJNP342928. lj hypothetical protein SS01493 [Sulfolobus solfataricus P2] MKDAETLDFALVEVSNWWKKAVLTGELTGKDVIKAITIVKEYLPQLLTVNKSIDLIERAI EISVNEKITVYDSLYIALA ECKGSKLVTGDKKQYDVAKKYVISELI >vapBI15896971 : cl503996-1503685, length 104, Sulfolobus-solfataricus, VapB MNFRSDPQSSIQSKLYIHTHLFTFVSKIIRVSEDVKEKLVKISAELELSEGKRVSLNDTI KYLITLYEEKKSNKNSELLLSLLGSAKGIREEFERSRIEDESSD >gill58984691refINP_343074. 11 hypothetical protein SS01651 [Sulfolobus solfataricus P2] MKWTDTGVLVEVLEGSKLGEKFIQLVDSGKIEPIITNLTLIELSYIICRKYGIDKARELV KKLLDSNYFEWNAFDFAE NIVEIKCNNSLSIIDASVIATAKALGISALFKMEKELKDKKFNNLIFIENL >vapBI15896971 : cl577585-1577400, length 62, Sulfolobus-solfataricus, VapB MKEGDILILRVEDGKIVLEPERKVSFDDLKKKMEEHSAKISYANKAKLGDLINVSLEEEF DN >gi15898541refNP_343146. 1 hypothetical protein SS08813 [Sulfolobus solfataricus P2] MRLFTLSKKKYNVKFEDTIDFLDKIILPYTIILPINSHDYEKAKGIMISKTLKPSDAFHV AVMINNSIKKIVSEDSDFDK INGIERIWVK >vapB) l5896971 : 1582391-1582642, length 84, Sulfolobus_solfataricus, VapB MGIQNQLMGYIVTVDERGRIVIPKDIRERLNLKEGSKVEISVDEKGRIIIIVRRISVDNI YGIAGRERVSIEEIEEALGFEDND >gi15898547refNP343152. lj hypothetical protein SS01746 [Sulfolobus solfataricus P2] MKIMIDSNVFIYVLFSDPSYGERAKELLNKAENEDAYSSTLIISQVLAHLERRRKSEIIP VFINYIQQSGIKILETRWED VIEAIKLLRNMNLSYNLWDDAIISAQIKREKIDIIFSNDKDFDILQVKREF >VaPBI15896971 : 1620321-1620638, length 106, Sulfolobus_solfataricus, VapB MIHLLRIRKFYNIRMSYFLHMPIISIRIDEKLKKKMDELSYINWSEIIRRKIEEVIEEEE EKRKGKRKDYKKIAEASVRSYEFFLNYGGKSSEEIIREWRDKNWQL >gi|15898585|ref|NP_343190. 11 hypothetical protein SS01786 [Sulfolobus solfataricus P2] MERQELAWDASWIKWFVNENYSKEALILKEAYVKGLEDLLAPCILPFEVLNGLKYTYSLG EKELEEVGKILSDFQITL YGFENILDEMVSLSLRYGITIYDAAYIALGKVLNEKVYTADERLIRKVKELPFVIHIKDY KQK >gil5898659refNP_343264. 1 hypothetical protein SS01867 [Sulfolobus solfataricus P2] MIKLKRVYDPIERDDGIRILVDRLWPRGIGKDKVDLWLKDIAPSDELRKWFSHDTSKWDE FKKKYFEELDANPKISVLLQ LIKKGENITLLYASKSPYNNAVALKEYLEKKILKQ >gill58986601refINP-343265. 11 hypothetical protein SS01868 [Sulfolobus solfataricus P2] MLKSPFEATILIEEHPCEVMKIISSTGLKGWDNVKLGDNTTDHIVLFEKEVQKDDLIKLK SHSTKVLRLNDNKIWVRTY GCAVCKILYTSNVWEKIKWRERTLLYTLLIPNTMALKEFLASLISQDIEFTVLSTSEISS NELTDRQMEILKLAYKMG YFDDDRRVTLTELAKQLGISTPTLEEILRRALRKWKFYLDKVR >VaPBI15896971 : cl734033-1733776, length 86, Sulfolobus-solfataricus, VapB MFTIKENTMTSTVISIRVDERLKKELEELGIDYPELVRRYLEEWRKEKMRRELREANGI REELLKSHGYYSPSAELVREDRDGYH

>gi|15898712|ref|NP_343317. 11 hypothetical protein SS01914 [Sulfolobus solfataricus P2] P2] MAIIDTSALFAIYFPEKYVEECYFLDLIFYEFPNVIRKRDVRNELSREKADEILLRALSY IDLCKYVSGK ELTMTAYEISI. KYSLTTYDASLIALAKKVGDVILTADEKLLRGIRNFPEISKYFIFP >vapBI15896971 : 1742082-1742303, length 74, Sulfolobus_solfataricus, VapB MSTVISVRIKKEIKEELEKHGVDIDQEVRKFLEELYLKVKAKEYINKWIEDLKDVKPSEE GFSSNSVREDRESH >gi|15898722|ref|NP_343327. 1| hypothetical protein SS01922 [Sulfolobus solfataricus P2] P2] IEAFKIANRNKITVYDSLFIALAKSNNLELVTSDKKQYEVAIKEGVNTRLI IEAFKIANRNKITVYDSLFTALAKSNNLELVTSDKKQYEVATKEGVNTRLI >vapB|15896971 : 1783470-1783712, length 81, Sulfolobus_solfataricus, VapB MYLMEVKVHKKGIIVIPAEVRRRLNIKEGSVIELEVEGDKIILKRKLTLLDAYGIDKEMG DSAVKELEKLRKEEVEKENSV >gi|15898766|ref|NP_343371. 1| hypothetical protein SS01969 [Sulfolobus solfataricus P2] MRRKILFDTGFFHVYFSGLNEEAKKAVEEVYTGKSVGYTLDLNLAEFLYTYGKLNGVEEA NVRLSLILNSPIKIVSTNKE LALRAGELKVKYQNLSIVDCFLVAFAEKENTVIYTTDSEIKRVYMTIILHS LALRAGELKVKYQNLSIVDCFLVAFAEKENTVIYTTDSEIIZRVYKNTTTLHS >vapB|15896971 : 1784438-1784701, length 88, Sulfolobus-solfataricus, VapB MYESFIYVYFVYIYMSDVISVRVKKELKKRAEELGINIREWEKALEEAIREKEKEELKD IVMRIKELMRDVSEDDWVRAVRESRDER >gi|15898767|ref|NP_343372. 1| hypothetical protein SS01970 [Sulfolobus solfataricus P2] MKDKEFLFDASALYSLLDYVDKIDLKKIHILTLTFYEVGNVIWKEYYIHKKVKDPITLSM LFHKLMRKLNIVEDPPLEGV MRIAVERGLTYYDASYAYVAESLGLILVSNDKELIRKANAISLKDLIKSM MRIAVERGLTYYDASYAYVAESLGLILVSNDKELIRKANAISLKDLIKSM >vapB|15896971 : cl788331-1788080, length 84, Sulfolobus_solfataricus, VapB MYTSYMKTIMIRDDVYKKLVEIKGDKSFSEIIEELIEESLTLRRRKLEKYFGILNEEEAE EIMKEIKEVRKITDESINRKLSNY >gi|15898771|ref|NP_343376. 1| hypothetical protein SS01975 [Sulfolobus solfataricus P2] MKVLIESSAIIEYLKGNAKVKEIISNSEDFYVSTLTIFEVLLGKVEENKILDFLSAFNVI GLNKKDSIIASRIYKRLRDK GKLIGYFDILISAQAINRDLTLVTKDTDFLKVADEFNELKVALIT GKLIGYFDILISAQAINRDLTLVTKDTDFLKVADEFNELKVALIT >vapB|15896971 : 1914151-1914375, length 75, Sulfolobus_solfataricus, VapB MKSTITVSKKVKEVLERKKKEMEIKLNKPLSWDEFFQNIFREEEERIPKLTEEEAEILKD LTKEDRKNWRIREFV >gi|15898880|ref|NP_343485. 1| hypothetical protein SS02096 [Sulfolobus solfataricus P2] P2] KMGEIIEDPDLLIASICIANDFSLMTHNKKHFKRLEKYGLKLI KMGEIIEDPDLLIASICIANDFSLMTHNKKHFKRLEKYGLKLI >vapB|15896971 : c2041164-2040874, length 97, Sulfolobus_solfataricus, VapB MSATNSLLYKDLNAIEIIFVNPIFYYLRSWIPPKSLILRLEDKGYPQTARVWDGEWT LIKTNQEITVRVSQHKAKILRFFKLDLIGEVLHAYHI >gi|15898992|ref|NP_343597. 1| hypothetical protein SS02219 [Sulfolobus solfataricus P2] P2] MHIIFDTSGFLSGLQLSLDRVYTTQEVINEIKDKYSRFNLEIAISSGKVIIMKPSTRSVE KVTKVLNLTKERKLSNTDIS VIALALDLQPSIVFTDDLSVQNILKQLGIQFSSVKINKKVEKSFKFKYVCVNCKREFNID HGECPYCGGKWKRRIME >gi|15899834|ref|NP_344439. 1| hypothetical protein SS03128 [Sulfolobus solfataricus P2] MERRRVKVYKKGIIVIPKEIREKLGIKEGDIIELIVNGDRISIEKPLTLLDLFGIDGDEA LEIAKEIIKERRKEVEKEIR S >gi|15899833|ref|NP_344438. 1| hypothetical protein SS03128 [Sulfolobus solfataricus P2]

MRKKYVLDAGPLSLLFAGRKEIKKYFEEIYTGDAIIYMSEVNLAELLYIYILKKGKDVAI ARHRYIRNSPIKVISPNERI TENAALLKSKYSYLSLADAFLIATAKEVKGKVITTDEDIEKTKEVETIKIPLD >vapB|24473558 : c2516-2271, length 82, Sulfolobus-tokodaii, VapB MFSVYVYYNMKTVYSLRIDKELREEMEKYNIKWNEEIENFIRRRIEELKKEEILKKINEI LQTMPETNSSSAELVREDRDNN >gi|15920165|ref|Ns_375834. 1| 96aa long conserved hypothetical protein [Sulfolobus tokodaii str. 7] MEVSNWWKKWVLTRELTEQDAIKAVTIIKEYLPQLLTLNKSVNLIERAMEISVKEKIPIY DSLYIALAERKGSKLVTGD KKQHEIAKKYVISELI >gi|15920187|ref|NP_375856. 1| 77aa long conserved hypothetical protein [Sulfolobus tokodaii str. 7] METITKVNKKGIIVIPKGIRDEIGLKEGDAVKITVEGNKIVIEKIDLWDKVWNCCKGSAE EAEKELDEEEGEFWKRK >gi|15920188|ref|NP_375857. 1| 129aa long hypothetical protein [Sulfolobus tokodaii str. 7] MAFGELTERGKEIMLRIKDRKIEGIITSTVAYEFTVHWFRGRIPALKSLDEVKSFLNSYF KIVELSVDDFLESARIKSEG DKIVSLKGRKLSIVDSTLIQTAKKLGLKILSGDKDLTLVATKMGIEVIW >vapB|24473558 : c397414-397157, length 86, Sulfolobus tokodaii, VapB MENYQLLERWGAKELVKVENIKKGEVLMLTLGSATTLGVAKNIKNDELEVELKRPLWW DKDLRWISRQVSGRWRLVGWGIIKI >gi|15920583|ref|NP 376252. 1| 143aa long conserved hypothetical protein [Sulfolobus tokodaii str. 7] METSRLGNNKNLGVLVDTNILLYIYHGFDPFEKIIQFLDYKPVFYIPNIVLKELNKFLNS KSIIMNKKANLALQYLNTYK NYWKSIEGYENMRVDDALIQICKDYDLFLFTNDTRLRHKAKLKGVRVIYLRQKSKNIKVD III >vapB24473558 : c673537-673358, length 60, Sulfolobus tokodaii, VapB MLERKKKEMEIKLDKPLTWDEFFQEVFKEENIPKLTEEEAETLKKLVLEDRKNWKVREFA >vapB24473558 : c673537-673358, length 60, Sulfolobus_tokodaii, VapB MLERKKKEMEIKLDKPLTWDEFFQEVFKEENIPKLTEEEAETLKKLVLEDRKNWKVREFA >vapsl24473558 : 761620-761892, length 91, Sulfolobus_tokodaii, VapB MLLQSDNVMSETIRVSKEVKRELLKIMGELQIERGEKVDFNDVIEYLLSLYRRKNPEILR RMVGLVPNISYEDLRKERKKELEYEKEKYGI >gi|15921016|ref|NP_376685. 1| 131aa long hypothetical protein [Sulfolobus tokodaii str. 7] MVFDSGWIDILLGSNEGKKIEKFIEENLDEIVINELNLEEIKYIICRKNNVEKAEEVEIF LKSSGYFNVFPFTNVRGEI YRLKCKYPISLADASSIATAKILGIPAMFKREKEIEPFKNELNVIFTDELI >gi|15921133|ref|NP_376802. 1| 68aa long conserved hypothetical protein [Sulfolobus tokodaii str. 7] MRLPKELKEKMEKYEVDWDQLIKDFIEKKVEELERENHAKKAKELLSSIDLSTNGFAIKE VRRHREGN >gi|15921134|ref|NP_376803. 1| 125aa long conserved hypothetical protein [Sulfolobus tokodaii str. 7] MKGENWDRIIEYIPNGITLDISYYEVLNVISSAKKKKIVDKEKSKVLYDAVNELMKSMKV YSAYNYLKEGFEISNEYNIS LYDGLFLALALSHNAELLTFSRNQIKVATKLGITYNKDLLMNHEY >gi|15921355|ref|NP_377024. 1| 78aa long conserved hypothetical protein [Sulfolobus tokodaii str. 7] MKVKVHKKGIIVIPADVRRRLNISEGSYMELEVEGDKIILKRKMTLLDAYGIDKGMGDLA LKELEKLRKEEVEKENNI >gi|15921356|ref|NP _377025. 1| 107aa long hypothetical protein [Sulfolobus tokodaii str. 7] MEEVYMGKSQGYTIDLNLAEFLYTYGKLKGLEEARVRLSLILNSPIKIVSTNRELALRAG ELKVKYQNLSIVDCFIVALA EKENAWYTTDSGIERVYKNTKVILHS >vapB|24473558 : cl303456-1303313, length 48, Sulfolobus_tokodaii, VapB MENVSTGSEIIERLKKLGVEEKDLIVEPPQGEEEFQKELKRKSMIQMF

>VaPBI24473558 : cl303456-1303313, length 48, Sulfolobus-tokodaii, VapB MENVSTGSEIIERLKKLGVEEKDLIVEPPQGEEEFQKELKRKSMIQMF >gi|15921894|ref|NP_377563. 1| 125aa long conserved hypothetical protein [Sulfolobus tokodaii str. 7] MFLDKKEMRDMLKIKRIYDPVEKDDGIRILVDRLWPRGVRKDKVDVWLKDIAPSDELRTW FNHDPNKWEEFKKKYFEELS KNPKLDILLQLIKKGENVTLLYTSKSPYNNAVALKEFLDKIFKAS >gi|15921893|ref|NP_377562. 1| 204aa long conserved hypothetical protein [Sulfolobus tokodaii str. 7] MPKSPFEVTLLIEDHPCEVMKLISTMGLKASVENVKLGDNVTDHIVLFDNKVKNEDVLKL KSGNSKVLRLSDNRIWVRTN GCSVCKVLYTSDVVEKIKWKERTLLYTLLIPNTSSLKEFLSKLTSQGVKVTVISTNEITG NELTERQMEILKLAYRLG YFDDDRGITLTELANRLNVSAPTLEEILRRALRKWKYYLDKVG >gi|15921930|ref|NP_377599. 1| 88aa long conserved hypothetical protein [Sulfolobus tokodaii str. 7] MFTKEENIMTTTVISIRVDEKLKKELEELGIDYPSLVRSYLEEWRKEKMRRELKEADRIR EELLKSHGYYSSSAELVRE DRDNNDYY >gi|15921931|ref|NP_377600. 11 155aa long hypothetical protein [Sulfolobus tokodaii str. 7] MDIILLLQNSLEKIGIIMTIIDTSALFALYIPEKMSAFIRKEIENVDECYVLDLIFYEFP NVIRKRIVRNELSKEKGDEI LARGLSYIDLCKWSGKELAKTAYEISLKYSLTTYDASLIALAEKVNDIILTADEKLIRGI RNVQEISKYFIFPD >gi15921943refNP_377612. 1 100aa long hypothetical protein [Sulfolobus tokodaii str. 7] MGVNLIIYEFDSLHMPVISIRIDEKLKKKMDELSYINWSEIIRRKIEEVIEEEEKKKKGK RKDYKRIAEASVKSYEFFLN YGGKSSEEIIREWRDKNWQL >gi|15921942|ref|NP_377611. 1| 109aa long hypothetical protein [Sulfolobus tokodaii str. 7] MKGLEDLSAPCILPFEVLNGLKYTYSLGEKELEEVGKILSDFQITLYGFEDMLDEMVSLS LRYGITIYDAAYIALGKVLN DKVYTADENLIRKVKELPFWHIKDYKQQ >gi15921944refNP_377613. 1 110aa long hypothetical protein [Sulfolobus tokodaii str. 7] MMSLTSDEKTLCKIVYKVNFIYISSDFFHVTEVIRVSKDVKDKLVKIAAELQLSKGKKVS LNEAIGYLITFYEENKRSKK DSQLLISLLGSAKGIREEFERSRIEDESSS >gi|15921945|ref|NP_377614. 1| 134aa long conserved hypothetical protein [Sulfolobus tokodaii str. 7] MRVVVDTGVLVEVLEGSELGEKFIQLVSRGKLEPIITNLTLIELTYVICRRYGTDKAREL IMKLLDSGYFKLVNALDFAD EIVKVKCNNSLSIIDASVIATAKGLGITALFKMEKELKDKKIDNLIFIENLINI >vapC24473558 : 1818807-1819082, length 92, Sulfolobus-tokodaii, VapB MLFYVYENFIYTKIVYLIMSTVISVRVRKELKEKAEELGINIREWEKALEEAIREKEKE EIKETARKIKELMKDISEDEWITSIREDRYER >gi|15922115|ref|NP_377784. 11 130aa long conserved hypothetical protein [Sulfolobus tokodaii str. 7] MRDEFLLDASALYPILNYIDKIDVAKIYIIPLAFYEVGNTIWKEYYLHKKIKDPIILSAL FQKFMSKLKLLNSPPAEEVM KFAIEKELTFYDAAYVYSAASHGLILVSEDKELIKKANALSLKDFISKLS >gi|15922247|ref|NP_377916. 1| 127aa long hypothetical protein [Sulfolobus tokodaii str. 7] MVDYIARYVLRDREIIVKYTAENDDESIKLANSVCEKLGERDIEEVIIGKIVGTITGAIM WHSISEDNSITTAIFSAITN ALIGHIVDNLIVKEIYSKKYPCIRPRQLSDLHKYIDIRKLEDAVNAR >gi|15922248|ref|NP_377917. 1| 185aa long hypothetical protein [Sulfolobus tokodaii str. 7] MHVDEVLQKCDQTYVIFDTSIILDYIRLSSRDKNHRLEVLSYIINNCRNKVITLLNLEEI LVGNIGNKEEIENFIFYSFK ILNITEKEAEVTAELEVKVREEGLGFKGENWRIDLFIASFAYTRSYYILTKDSDFKKILD CKLHLLHIIHYLELHAQGIQ RPTTPNYSKLTNMFCIWKSDYQTDG >gi|15922315|ref|NP_377984. 11 75aa long conserved hypothetical protein [Sulfolobus tokodaii str. 7] MERIIRIGKRNAIYIPKEIADSLNLKEGDRLVLWKDDKIELIPVRKPSKYWAEISPDEVE EVGEEINKSLGVNS

>gi|15922315|ref|NP_377984-1l 75aa long conserved hypothetical protein [Sulfolobus tokodaii str. 7] MERIIRIGKRNAIYIPKEIADSLNLKEGDRLVLWKDDKIELIPVRKPSKYWAEISPDEVE EVGEEINKSLGVNS >gi|15922329|ref|NP_377998. 1| 70aa long conserved hypothetical protein [Sulfolobus tokodaii str. 7] MSTVYSIRIPKKLRELMNLVNVDWQKEISKYIEDRVREELIRKYIEEGRKNLAKMKNISN ADLIREDREA >gi15922330refNP_377999. 1 117aa long conserved hypothetical protein [Sulfolobus tokodaii str. 7] MIKIIEGSDEDFLTLDLAFAEVSNVAWKRIVIFNDDYNITLEQLKNALDFIEKLCKIVYV KDITMEAINLAVQEKLPFYD SAFLYLAIKEGTKLLTTDLKLFNKLNDKLKNYVIVPE >vapB|24473558 : 2138189-2138767, length 193, Sulfolobus_tokodaii, VapB MPILGVKFGRRSALLDIRPENIKEALELLQKNKYTIEEYPMLEAKSKNINTIAFNEIAIL FNNPETVYGSVNIKERKILFEGDGVLIATPQGSWAWSYSATRVLLHKDINGIEITFINPI IPNIKALIIPQTETILVKLEDKGRTQNVRVISDGEIVGNLISKEDEELTITLSKRKAKIL RFFNLIEFDGLFT >gi|15922464|ref|NP_378133. 1| 162aa long conserved hypothetical protein [Sulfolobus tokodaii str. 7] MDYSHKIVFDTGAFLAGLQNYYEKIYTNSLVINEIKDKKSRELLDLAIMAGKIIIMEPEE NTLKKTKKIAEKISAYNLSK TDLSIAALAYELRPSIVFTDDLTLQNLLLNLGIEFKSVKLNIRIRNRKKYKFTCKACGKT FSRSYSSCPYCGNTIIWSY NE >gi|15922519|ref|NP_378188. 1| 81aa long conserved hypothetical protein [Sulfolobus tokodaii str. 7] MEKYRVKVYKKGIIVIPKEIREKIGIKEGDILELTVNGNKIDIEKPMTLLDLFGVDGEVA VEVAKEVIKERRKEVEREIR s >gi|15922520|ref|NP_378189. 11 105aa long hypothetical protein [Sulfolobus tokodaii str. 7] MYTGSIEIYMSEVNLAEFLYLYILKMGKEIAIARHRYIRNSPIKILAPNENITQSAAILK SKYHYLSLADVFLIATAKEI GGKVITTDEDIEKTKEVEVIMIPLD >gi|16330048|ref |NP_ 440776. 1| unknown protein [Synechocystis sp. PCC 6803] MLRELRTNRASWKIFTGKKLRKQYLLSLISTQRSSLDNTKEGQAILKKVHSFYKMMLQEL EAVFDGTALQLEVPLNLAAG TRVRIWESVLPNEVKAPKTFLQTAQSLKLQGEPDWSEKIDQYLYGETLSDND >gi|16330047|ref|NP _440775. 1| unknown protein [Synechocystis sp. PCC 6803] MNLIGQRKLINICMGKLFLTMTEVFLDTSFAIALSSITDQNHVRAIQLANQIEANKIRLV TTQGILLEIGNALSKQRYRK AAIQLLESLETDPSVEWLLTNSLYKSAFNLFKQREDKEWGLVDCISFIVMQDRGITDVLT ADIHFQQAGFRALLRD >gi|16330685|ref|NP 441413. 1| unknown protein [Synechocystis sp. PCC 6803] MNTQLVESLVQIIQSLSPEEQKLLETHLAEKNSNWQEVLGKIETNRQEIYASRQGKPFDL SIDEIIEEMREERTQDVLQA CFGK >gi|16330684|ref|NP_441412. 1| unknown protein [Synechocystis sp. PCC 6803] MTNQTSFTICIDSNFIVRLLVGYYEETIYLEMWNKWCNANTKIVAPDLINYEVTNVLWRL NKTNQINYTQAQIALTESFN LGIELYSNSELHQDALAIAEKFQLSAAYDVHYLALAEKMQIDFYTCDKKLFNSVQQNFPR IKLVIANSS >gi|16330930|ref|NP_441658. 1| unknown protein [Synechocystis sp. PCC 6803] MTTEAALLNIAENLPDDLKIELLHYAEYLMNKSLNAPQKPLAGSMKGTFILPLPEDFDAP LEEFEEYM >gi|16330929|ref|NP_441657. 11 unknown protein [Synechocystis sp. PCC 6803] MNSVLIDTHVFIWLAEDDSNLPVTTKDTLENMDNVFVSIASFWEISIKLKIGKLSLCGDF NSIEASFQRTRFKLLPITLK DTIKLYNLPLHHKDPFDRILVSQSINHSLILVSRDQALDDYPIQRLWL >vapB|16329170 : c2516782-2516531, length 74, Synechocystis_PCC6803, VapB MDTKSKLRSNPMTDTALLEKINALPDAMKIEVEHFVEFLLTKQPPVSPVTNDGQKKYRQA GVLKGKIWMADDFDAPLEEMQEYM >gi|16331422|ref|NP_442150. 1| unknown protein [Synechocystis sp. PCC 6803] MLLDTHTLLWFLDNDIKLPSHLKSLIEAKPKVYVSIVSLWEIAIKLNINKLRLNYAFTDL ENLLADLNISVLNITWQHLE ACRNLPLHHRDPFDRMIIAQAQQHNFSVISKDENFKKYNVNLIWE

>vapB|16329170 : c3044422-3044670, length 83, Synechocystis-PCC6803, vapB MEQNRMKQITPTELRGNLYNLLDEVLATGIPLEINRGGKRLRILPVEEPDKFKNLVHRPG VIIGDPEELVTIDWEGEIELDLP >vapB|16329170 : c3044422-3044670, length 83, SynechocystisPCC6803, vapB MEQNRMKQITPTELRGNLYNLLDEVLATGIPLEINRGGKRLRILPVEEPDKFKNLVHRPG VIIGDPEELVTIDWEGEIELDLP VIIGDPEELVTIDWEGEIELDLP >gi|16332080|ref|NP_442808. 1| hypothetical protein [Synechocystis sp. PCC 6803] MIGVSVNPEKLGSTMETVNVDQIEINLPELLYSIKPGEEVIVADQGIPIAKLVPLQRQKS VDRCSSLGVDRGLFWPDDF NDPLPNDIWPLS >gi|16332079|ref|NP_442807. 11 unknown protein [Synechocystis sp. PCC 6803] MKLLLDTQCWLWWFTEPEKLNEDAISQIIDETNEIWLSVASIWEMSIKTSIGKLPLPENI DDYILSRMVKLGAEFLDIKT RHALQVATLPLHHRDPFDRIIIAQAQTENMLLISADSMFKNYGVSLLWAGV ------------------------------------------------------------ ------- >gi|20807534iref|NP_622705. 1| Hypothetical protein TTE1060 [Thermoanaerobacter teng- congensis] MMQVSSTEFKNNVGKFLKLSEKEDILILKNGKPVAKLTAVSKNEKEIAYDRLLEMIKKSK PVTEEIDLKAAREERLNKYD SAT >gi|20807535|ref|NP_622706. 11 Hypothetical protein TTE1060 [Thermoanaerobacter teng- congensis] MIVLLDTNISLDFLLKREPFFEPASRILEMVKDDKIKACITASSVTDIYYIMRRYKSQEE RVLMLSEYLKLVEIISTTKT DIIKALKMKNTDFEDAAMFQSGKRRKVDYIVTRDKIEFTDKIVKIVTPEEFLRIVRK >vapB|16081186 : 38670-38828, length 54, Thermoplasma_acidophilum, VapB MTHVHFAGYRRWWGIYGKDLIAICWFEPVNILLVPVPDPLFFHLIYVYIHSDL >gi|16081221|ref|NP 393520. 1| hypothetical protein Ta0042 [Thermoplasma acidophilum DSM 1728] MPWVGSQFHKGDAQTIMALSNVLYQVLIALGMIYVIDTSAIISRNLNLLEGDLMFPSSVI GEIKKGKLRYMIDVLLPMIR VASPDHEYLKIVEETAAKTGDLMNLSQTDKDVLALALQYDATIVTDDYSIQNVASYLNLG FLNANIKRIDKQIAWIYRCT GCKKVFPGPVKVCDICGHEVKRHYDKRKSMIRKV >vapB|16081186 : 804192-804743,. length 184, Thermoplasma_acidophilum, VapB MSGYIARNTDIDIVLSSDYLREFLRPFAPQESHLETSVYDAWKFYGDMSDDNIIRGYLDQ ARPIMGGINRVIARALANGEDLIIESLYFVPDMMDEMVLKNAFLAYVYIDDPDLHRSRLE DRINYTHRNSPGSRLAAHLKEYRTIMDYSMDMARGRGIGLYSTDDYALARQRLLDDFRKF VDRR >gi|16081834|ref|NP_394227. 1| hypothetical protein Ta0762 [Thermoplasma acidophilum DSM 1728] MKSNFAIVDTNVIIYAMKSRVRLDELVLSLSGIARIAIPECVIYELRKLSAADINARIGL QYAMQHQVLKSEGHGDECIL KAAIKYGCPVITNDREFIEVLKRNHVWATLSGRKLVEMN >vapB|13540831 : c886266-885913, length 118, Thermoplasma_volcanium, VapB MDRILIRAIENGENLILETLYFLPEMLSEKARNNVHMFYLYIGDEKLHRDRLVDRINYTH KNSPGTRLAEHLYEYRNIMEYSMMRSSEYNVKIIDTSNYEEARRTILEMIVKGESRYA >gi|13541682|ref|NP_111370. 11 Predicted nucleic acid-binding protein, contains PIN domain [Thermoplasma volcanium GSS1] MKADTPNFILLDTNAIIYAIEKKIRLEDAVIEIPGVSRPAVPYCVIRELYGLAKKNVTAR IAYQYAKKLEIIETDKYGDD GVIEAAMKTGAMVLTNDERLSRRLRETGIKVAMISGRKILF GVIEAAMFCTGAMVLTNDERLSRRLRETGIKVAMISGRKILF >gi|21242627|ref|NP_642209. 1| Hypothetical protein XAC1884 [Xanthomonas axonopodis pv. citri str. 306] MEATVAERGQITLPKAVRDALGLTKGTTLKIELDGGRIILRKDVSEALRKVRGKFKLVDG LTSTDAAMRVIRGRAPGDPF DP >gi|21242628|ref|NP_642210. 1| Hypothetical protein XAC1884 [Xanthomonas axonopodis pv. citri str. 306] MIALDSSVLLDILIGDPVYGEVSEICIGDALARDEVVVCDAVVAEVLAMLDTQVDLMETL ASIGVRYEATQEAAAVRAGH MNKRFRARGGKRERWADFLIGAHAMLQCDGLITRDEGFFRDYFKGLKIWPKPAP ------------------------------------------------------------ -------

>gi|21231309|ref|NP_637226. 1| Hypothetical protein XCC1862 [Xanthomonas campestris pv. campestris str. ATCC 33913] MEATVAERGQITLPKAVRDALGLTKGTTLKVELEGGRIILRKSVDDAISRARGRFKLDGF ASTDDAMRAIRGRAPGDPLD PEAGA >gi|21231310|ref|NP_637227. 11 Hypothetical protein XCC1862 [Xanthomonas campestris pv. campestris str. ATCC 33913] MIAIDSSVLVDLLADSAQADAAEACLRQCLSTGPWVCDWLAEVCSALRDGAEALSVLEDM SIRFNALEAKSALRAGEM QRRFRARGGKRERWADFLIGAHAMLQCDGLITRDDSFFRDYFKGLKIIVPKPAA ------------------------------------------------------------ ------- >vapB|15836605 : 304978-305193, length 72, Xylellafastid. iosachr, VapB MDATVAERGQITLPKRVRDALGLTKGTVLKVELEGGRIILRKSVDDAIARARGRFILDDF GCSAIATKTDKQ >gi|15836896lref|NP_297584. 1| hypothetical protein XF0292 [Xylella fastidiosa 9a5c] MPSRRRRTSNETVIAVDFPVLVELLTDRPQADAVEAALRQCLVSGRVWCDWVLAEMSAVL RGGAEVLGVLEEMGVHFDP LEAKSALRAGEMYRRYRQRNATESDMKYFLVGAHALLQCDGLMTWNDAFYRDYFKGMKLI VPGA ------------------------------------------------------------ ------- >vapB|28197945 : 303404-303628, length 75, Xylella_fastidiosa_Temeculal, vapB MDATVAERGQITLPKRVRDALGLTKGTVLKVELEGGRIILRKSVDDAIARARGRFILDDL DDFGCSATATKTDKQ >gi|28198163|ref|NP_778477. 1| Hypothetical protein PD0235 [Xylella fastidiosa Temecu- lal] MIAVDFPVLVELLTDRPQADAVEAALRQCLVSGRVWCDWLAEMSAVLRGGAEVLGVLEEM GVHFDPLEAKSALRAGEM YRRYRQRNATESDMKYFLVGAHALLQCDGLMTWNDAFYRDYFKGMKLIVPGA Homoloques of relBE toxin-antitoxin system polypeptides >gi|14600379 : 984865-985164, length 100, RelB MLISVFLMRRVSECVRWKLLFNLHVTYYILADGGLIVSSKKSKVKVEVEVEVPEGDDEGV YREEFRRELAKRILNVMLDKDVEPAKRAVAKTLREKGGEG >gi14602207IrefNP 148022. 1I uncharacterized conserved protein [Aeropyrum pernix] MTEVYIESSAKRDLKRLPKHIVQWVLNTVEELEENPFIGERLHLPASLHGLYCFKLRRGD YRLVYCYVPNRDTVYIIAVG HRGEIYEKFRRRIK HRGEIYEKFRRRIK >gi15668172 : 840765-840947, length 61, RelB MSIVQSYITDEKGNIKGVILDYKTFKKIEELLLDYGLLKAMEEVENEEEIDLETAKKLLE Q >gi|15669099|ref|NP_247904. 1| conserved [Methanococcus jannaschii] MKQWKYLLKKSFIKDLKELPKNIQEKIKKLVFEEIPNKNNPPEIPNVKKLKGADSYYRIR VGDYRIGFKYENGKIVFYRV LHRKQIYKRFP LHRKQIYKRFP >gi|15668172 : c1043988-1044146, length 53, RelB MRLKKRFKKFFISRKEYEKIEEILDIGLAKAMEETKDDELLTYDEIKELLGDK >gi|15669291|ref|NP_248096. 1| conserved [Methanococcus jannaschii] MKVLFAKTFVKDLKHVPGHIRKRIKLIIEECQNSNSLNDLKLDIKKIKGYHNYYRIRVGN YRIGIEVNGDTIIFRRVLHR KSIYDYFP KSIYDYFP 20088899 : 1172771-1172992, length 74, RelB MNAIIAIVTIMSETTTIQISKDTRDELKAIGKMGDDYNTVIRKLIHEHNCNKLIEEGDRL IREHRDEFVSIDEL >gi|20089858|ref|NP_615933. 1| conserved [Methanosarcina acetivorans str. C2A] MSFKVLIHPKVFEKVPVDRRDQIKDALQELKDPLPGGNKKEVKGSHKTVYRLRIGDFRIL YEIDFERSEVLVFNIITAEQ AHKKYNRFK >gi|20088899 : 5035578-5035697, length 40, strand negative, RelB MQPTNLSLSCSKRFRNLQNTENEDPSERDLNIRIPFHIYY >gi|20092909|ref|NP_618984. 11 conserved [Methanosarcina acetivorans str. C2A] MIAMSNMDDELEEIRKRRLAEIQRQQAQQQPSDVQAAYQQEQARAEMEAQKQAILRQILT PEARERLTTLKMSRPALGEQ LEMQLISLAQSGRLKAQIDDEQLKTLLMRMQPKKRKTSITRV

>gi|18976372 : 841569-841447, length 41, RelB MWLIFAQNYCHNNKSLRKRYIWNLTFLHVKSHGALQEISC >gi|18977239|ref|NP_578596. 11 [Pyrococcus furiosus DSM 3638] MSKVMELYKKYLVERDPQQKLKFAKEILDNLLTLQLNPPIWETIRKSTGLKEHEMKEILN YLEEKGEIEIKRAKDGKKLY ASTIRSMKRKSKEIPLDMWISRH ASTIRSMKRKSKEIPLDMMISRH >gi23464628 : 1638836-1638570, minus strand 83, RelB MPRMQTRSDGREGRGAAPVQVRQSHQRAGAARAEPRQGRGNTPDQDTGRHEPMAQGKLRV RGQPQADQQLAQPGQTPQLETRR >gi|23464628 : 1638535-1638230, length 102, minus strand, RelE MEIKQSAEYRKWFKKLRDHKAKAAIQARLDACKLAGRPFGDIKPVGGPVSEMRFHTGAGY RVYFAMQGNVLMLLLAGGDKSTQQTDIRQAHDILNDYKEQRQ >gi|16124256 : 3371212-3371388, length 59, RelB MAEPDPDIFDEDDEAILAADAEADADFEAGRTVPHERVGEWLKTLGTPHQTPPPYSWRK >gi|16127361|ref|NP_421925. 1| conserved [Caulobacter crescentus CB15] MAQDVGHAAPDTATIFVAQWWTQRAMADVYAIVGHISEQSRPLAAQRLAKRLFDTGASLA TYPERGRVSTQGRREIVAI SPYVLRYRIVGDRWIGSVRHGARRPI >giI17934719refNP_531509. 11 [Agrobacterium tumefaciens str. C58 (U. Washington)] MANVEKISVSMTPQHAEILRDAVESGAYASSSEVIREAMRDWSAKWVQRRNDITKLRALW SEGKASGNSTEVDFDETLNE ARAELASLKNRDH >gi|17933925 : c809884-809573, length 104, RelE (starts at ATG or GTG codon) M VTTKLVWTPRARSDVKKIYVDIGKSQPLAAERYFARFRAKAESLIDHPHLGERHPEIFP SARMLVEAPYVILYETVPDTDDDEIRCVEIVRVNDGRRDLRTLF SARMLVEAPYVILYETVPDTDDDEIRCVEIVRVNDGRRDLRTLF >gi|15963753 : 1588987-1588739, length 83, RelB MRHPRNGLRPPGRQPRDLHGPGPDRRTELAGRVLRQSSARADQAVPQPDPALIRNNSKRR RPAFMAGRFVLYSKPKPRRNSPF >gi|15965227|ref|NP_385580. 1| CONSERVED [Sinorhizobium meliloti] MRFGYRRGLEFLPSARKEWDKLGATIRQQLVKKLRERLERPRIPSAALHGMPDHYKIKLR QLGYRLVYRVDDGSVTVLW AVGKRERVTSTT AVGKRERVTSTT >gi|30248031 : 1479043-1478798, length 82, RelB MYMAILNATEARARLYALIDEAAETHQPIVIKGKRSSAVLLSEEDWNAINETLYLVSIPG MRESIMEGMKTDVDECSRELDW >gi|30249331|ref|NP_841401. 1| conserved [Nitrosomonas europaea ATCC 19718] MWELRYTHQAQKDAKKLASSGLKDKAEELLAWRNNPYQTPPPYEKLVGDLAGACSRRINI QHRLVYQVLERERIVKVLR MWTHYV >gi|16129958|ref|NP_416521. 11 orf, [Escherichia coli K12] MNCTKEEIDMRTISYSEARQNLSATMMKAVEDHAPILITRQNGEACVLMSLEEYNSLEET AYLLRSPANARRLMDSIDSL KSGKGTEKDIIE >gi|16127994 : 2087233-2087487, length 84, RelE/YoeB minus strand MKLIWSEESWDDYLYWQETDKRIVKKINELIKDTRRTPFEGKGKPEPLKHNLSGFWSRRI TEEHRLVYAVTDDSLLIAACRYHY >gi|15799931|ref|NP_285943. 1| damage-inducible protein J [Escherichia coli 0157 : H7 EDL933] MAANAFVRARIDEDLKNQAADVLAGMGLTISDLVRITLTKVAREKALPFDLREPNQLTIQ SIKNSEAGVDVHKAKDADDL FDKLGV >gi|16445223 : c283932-284192, length 88, RelE/YafQ, minus strand MLNSGQFSKDVKLAQKRHKDMNKLKYLMTLLINNTLPLPAVYKDHPLQGSWKGYRDAHVE PDWILIYKLTDKLLRFERTGTHAALFG PDWILIYKLTDICLLRFERTGTHAALFG >gi|30063468|ref|NP_837639. 11 [Shigella flexneri 2a str. 2457T] MRTISYSEARQNLSAT MMKAVEDHAPILITRQNGEACVLMSLEEYNSLEETAYLLRSPANARRLMDSIDSLKSGKG TEKD

IIEWVMLPTY >gi|30061571 : c2077698-2077949, length 84, RelE/YoeB, minus strand MKLIWSEESWDDYLYWQETDKRIVKKINELIKDTRRTPFEGKGKPEPLKHNLSGFWSRRI TEEHRLVYAV TDDSLLIAACRYHY TDDSLLIAACRYHY >gi|15920437|ref|NP_376106. 1| 97aa long [Sulfolobus tokodaii] MTDKKPFALSEVAQRVLIVLGRENRGLTVRELVEKTDTNSGSIKRALEELAKLNLIKEEK ENVFPYRRLISLTEVGREVA KRVIEIEELVKKVQSNG >gi|15920438|ref|NP_376107. 1| 95aa long [Sulfolobus tokodaii] MAEEWKLVFHIKIKRLPREFQSDELERIEEALDKLSKMELNELDIKKLEGWNDNENRDIF RIRVGRDIRILVSFDNEKKQ IHIWRIARRESVYDE THIWRIARRESVYDE >gi|11498680|ref|NP 069908. 1| protein [Archaeoglobus fulgidus DSM 4304] MEVIQISKDELEEIIERKFKEVLIKALMEITPYVSDEEQEEIDKIAGKPDEYEGEFEEWH GK >gi|11498679|ref|NP_069907. 1| [Archaeoglobus fulgidus DSM 4304] MAWKVRYHKKAIKFLEKLDEGKRSILLSKIQELVNSLESGVLPIQRMDIKRLKGVWDGFL RLRVGEVRIIFKINVEDETI FIYSIHFREKVY FIYSIHFREKVY >gi|11498685|ref|NP_069913. 1| protein [Archaeoglobus fulgidus DSM 4304] MDIQVIKQAVREVLREELPSILKEVILSTIPPDEPEADEKQFVDEEINEDDYVKFDE >gi|11498684|ref|NP_069912. 1| protein [Archaeoglobus fulgidus DSM 4304] MNEVLIHKKFLDGLDSGRRSKVLDAIRMLKDFPIIRADIKKIGPKTYRLRKGEIRIIFDF DIGTNRVFVKFAASEGVFTK TEEKFF ------------------------------------------------------------ ------------- >gi|11498694|ref |NP_ 069923. 1| protein [Archaeoglobus fulgidus DSM 4304] MKVLLDIIEDIENFIRQLEKRRGELEELKDEILIFSDAEFIDSIQRGLSDLEQGRSKVCS NLEEVKKLFEDI >gi|11498693|ref|NP_069922. 11 [Archaeoglobus fulgidus DSM 4304] MNYKAQFSEEFLKIAKKLKEKDPELLKRLQSKVEEIIKQPEHYKPLRGQMKGLRRAHVGK FVIIFKVEEDTVKFVTFKHH NHAYK NHAYK >gi|11499924|ref|NP 071168. 1| protein [Archaeoglobus fulgidus DSM 4304] MNEALLREIYSEVKKIREKIEQLEELIIPAEKVSEEELLEIRKLKEESLKGEHVDWDELK RELGV >gi|11499923|ref|NP_071167. 1| [Archaeoglobus fulgidus DSM 4304] MFRVWHRKATQELKRLKKAHLKKFGVLLETLKTDPIPWKRFDVKKIEGEENTYRIRIGDF RVIYFLDKPTKTVHILKVE RRGKVYD RRGKVYD >gi|15789403|ref|NP_279227. 1| VngO069h [Halobacterium sp. NRC-1] MSNASKRIPVTEDRWEELNDLKGAGQTYDELLKELIQERNRSQLAERVRSVREADEDELT ALDDL >gi|15789404|ref|NP_279228. 11 Vng0070h [Halobacterium sp. NRC-1] MTYNVLLSEEAQEYYQQLDDKSQRIVKDNLTKLKDEPHPKPGSGAGDREKIPVDGETVYR LHIGRTHTALYDILEAEEQV RVIELLPIDEAHDRYGF RVIELLPIDEAHDRYGF >giI15668241refINP_247034. 1 M. jannaschii predicted coding region MJ0070 [Methano- coccus jannaschii] MLNINKEIAQIETELNELKKLRDEISERIEKLEIKLLKLKALAIPEEEFEEDYEEIIEDV KKSLDKKETVPAEEALKELG LL >gi15668242ref) NP247035. l) [Methanococcus jannaschii] MKFNVEIHKRVLKDLKDLPPSNLKKFKELIETLKTNPIPKEKFDIKRLKGSDEVYRVRIG KFRVQYVVLWDDRIIIIRKI SRREGAYKNP SRREGAYKNP >gi|15669361|ref|NP_248166. 11 M. jannaschii predicted coding region MJ1172 [Methano- coccus jannaschii] MILMVKAIVDITDENNRIINIVKAKYNLRDKSQAINKIIEEYAEFLLEDELKPEYIEKIR NIMKNEKPIYIGSIENLKKR YLGE >gi|15669362|ref|NP_248167. 1| [Methanococcus jannaschii] MYEIEIMPSLDKILQKLSKRDKKKLKAILKKMEEITQNPHHYKNLRHPLNDFKRVHIDKS FVLVFTVDENNKTVIFVDFD HHDNIYKKKKLFKD HHDNIYKKKKLFKD >gi|20088947|ref|NP_615022. 11 predicted protein [Methanosarcina acetivorans str. C2A]

MAETTTIQIKQSTKEALERMKIYKRETYNDVLERLIEDVQELNEETEKEIELARKAVEKD RYITHEKLKEELGF >gi|20088948|ref|NP_615023. 1| [Methanosarcina acetivorans str. C2A] MRFQIVWSKPAAEQLRKLDRPLAKRIFRKVSELQEDPFRYVTKLVGSPNYRLRIGDYGVI LEIQGSLLVILVLKVGHRRD IYK >gi|20089272|ref|NP_615347. 1| predicted protein [Methanosarcina acetivorans str. C2A] MAATTTICLEPEVKELLNGLKIHPQESYNSWKRLATNAYDWEPLSEESIKQIEEGLRDYR EGKFFTHEEVWGEIEKERR GRTGKTKVEECTE >gi|20089273|ref|NP_615348. 1| [Methanosarcina acetivorans str. C2A] MYRIIYSPAAKRDLKRLPADVQDRVHDALEEIADDPYAHVKKLKTPYNSPIFAYRVGKYR VIMSIHDFELIILVLEVGDR KNIYRKF KNIYRKF >gi20090545IrefINP_616620. 11 predicted protein [Methanosarcina acetivorans str. C2A] MKSVHVLRKFSGKKYGTKKTHLGTKKAYPPEECLNPEFIKEVECSRQKVLNGKGIKFNTV DDFFSNLEK >gi|20090546|ref|NP_616621. 1| [Methanosarcina acetivorans str. C2A] MTYQWLSPDFEKETKIFFKKDPVLYGRFKKTVNSILENPECGKPLRNVLKGLRRVHIGHF VLIYEIDNTNETITFLKFS PHDKAYK PHDKAYK >gi|20091001|ref|NP_617076. 1| [Methanosarcina acetivorans str. C2A] MILFFYYMVNMAQAIINIDDHTKKILDIIKTRYDLKDESAAIELMATQYEEEILEPELRP EFVEKMQNIMKEEPIDIGTI EDLRARYGH >gi|20091002|ref|NP_617077. 1| [Methanosarcina acetivorans str. C2A] MYRIKISPKLDEIIQKLDKKNKKQVDIILKKAGEIAENPHRYKNLRAPLNNLKRVHIDKH FGYC ------------------------------------------------------------ ------------- >gi|20092309|ref|NP_618384. 1| predicted protein [Methanosarcina acetivorans str. C2A] MTLNRVLGALYKRIELMGMTFTEIFYHLKELEKRFNEIKYPPEATFQPSFSSKIRKAERY CSKYNLPEFEIEEFFEKVEQ >gi20092310refNP-618385. 1I predicted protein [Methanosarcina acetivorans str. C2A] MTYRVAVHSSVRKNLKKLYKLDRPAYDYVKARLRLLAYKPEMGYPLEAEFGGKWRIHIGP FVLIYTFDKVNSTLTLLVFE HYTRAYDMDTAYA ------------------------------------------------------------ ------------- >gi|20093070|ref|NP_619145. 11 predicted protein [Methanosarcina acetivorans str. C2A] MMATITLPVPDELYMRMEHFSWVKWSEVARNSIRKREIFEKYLRSGELSDEDAEFCDKTD WHPADELPLREDYVQRLEDL KKETPLKVRDVSDIFE >gi|20093069|ref|NP_619144. 11 [Methanosarcina acetivorans str. C2A] MVRMPYDLFILPSCKKEIDKACKNNTLLKESLSKKIQEICESPFHYKPLRNELHGMRRVH ILKSFVLIFNVDENKKSVTL VSFSHYDTAYSR VSFSHYDTAYSR >gi|21227970|ref|NP_633892. 1| conserved protein [Methanosarcina mazei Goel] MHMIQARVKMSDRTNQVLNIVKAKYNLKDKSAALDLWAQYEEKILEPQYSPEFIKEMLDS ESDEVIGPFKNADELKAYI KSLPDEDE >gi|21227969|ref|NP_633891. 1| conserved protein [Methanosarcina mazei Goel] MIKGKLLKELRKLNKKNHVLFEAVFKKADEMCINPQHYKNLNYPLNKYKRVHIDSNFVLC FSVDEKE ------------------------------------------------------------ ------------- >gi|21228652|ref|NP_634574. 11 protein [Methanosarcina mazei Goel] MVQAIINIDERTNRILNIIKAKYGLKDKSAAINKMAEEYEEEILEPELKPEYIEKLKKIE KQEAIEVGTVENLRKRYGL >gi|21228651|ref|NP_634573. 11 [Methanosarcina mazei Goel] MYFLKIRSELDSKFEKLAKKNKKQLEIILAKADEILENPHRYKNLKAPMNHLKRVHIDKH FVLVFSIDEESRSVTLEDYD HHDKIY HHDKIY >gi|21228701|ref|NP_634623. 1| protein [Methanosarcina mazei Goel] MYMTFAEIFNQLKELETKFNEVSYPPENAFLPSFSFKIRKAEKDCLQHDLPAIDVDDFLE KVEQ >gi|21228702|ref|NP_634624. 11 conserved protein [Methanosarcina mazei Goel] MTYKVAVHPSVRRNLKKLYTLDRPVYDYVKRRLTLLVYKPEIGSPLGEEFQGKWRIHIGP FVLVYTFDSASNILTLLVFE HYTRAYDMNTAYT HYTRAYDMNTAYT >gi|21228706|ref|NP_634628. 11 conserved protein [Methanosarcina mazei Goel]

MSEATTIPVTKDIRDRLKKYGMKGETYNDILKRLMDEVDYETFMERQYKKLEEKDKFVSL DEL >gi|21228707|ref|NP_634629. 11 conserved protein [Methanosarcina mazei Goel] MSFDVKLHPDAVKFLVSLNPETKERLKSGIKNLEMDPFKSRPHADIKKLKGTKKRNDLYR LRIGDYRMIYSVEENTIFIL EIIPRERGYDWL ------------------------------------------------------------ ------------- >gi|21228783|ref|NP_634705. 1| protein [Methanosarcina mazei Goel] MIYMVQVDISDDTNQILGIVKTKFNLKDESAAIDFIVAQCEIDMLEPELKPEFIEEMQNI IAGKHIGPFKTVDDLKAYIE SLPDEEEDELCMK >gi|21228782|ref|NP_634704. 1| conserved protein [Methanosarcina mazei Goel] MYEIIISEKLSKKLIKLRKKNILQFNAIFKKAEEIQIDPQRYKNLRYPLNNLKRVHIDSH FVLLYSVDEETKTIILEDFI HHDFAY HHDFAY >gi|14590323|ref|NP_142389. 1| protein [Pyrococcus horikoshii] MRMEKVGDVLKELERLKVEIQRLEAMLMPEERDEDITEEEIAELLELARDEDPENWIDAE ELPEPED >gi|14590322|ref|NP_142388. 11 protein [Pyrococcus horikoshii] MTYRVKIHKQWKALQSLPKAHYRRFLEFRDILEYEPVPREKFDVIKLEGTGDLDLYRARL GDYRVIYSVNWKDKVIKIL KLKPRGRAYK KLKPRGRAYK >gi|15608387|ref|NP_215763. 1| protein Rv1247c [Mycobacterium tuberculosis H37Rv] MAWPLGEVRNRLSEYVAEVELTHERITITRHGHPAAVLISADDLASIEETLEVLRTPGAS EAIREGLADVAAGRFVSND EIRNRYTAR >gi|15608386|ref|NP_215762. 1| protein Rv1246c [Mycobacterium tuberculosis H37Rv] MSDDHPYHVAITATAARDLQRLPEKIAAACVEFVFGPLLNNPHRLGKPLRNDLEGLHSAR RGDYRWYAIDDGHHRVEII HIARRSASYRMNPCRPR HIARRSASYRMNPCRPR >gi|15610002|ref|NP_217381. 11 protein Rv2865 [Mycobacterium tuberculosis H37Rv] MRILPISTIKGKLNEFVDAVSSTQDQITITKNGAPAAVLVGADEWESLQETLYWLAQPGI RESIAEADADIASGRTYGED EIRAEFGVPRRPH >gi|15610003|ref|NP_217382. 1| protein Rv2866 [Mycobacterium tuberculosis H37Rv] RADIYRR RADIYRR >gi|15610493|ref|NP_217874. 11 protein Rv3357 [Mycobacterium tuberculosis H37Rv] MSISASEARQRLFPLIEQVNTDHQPVRITSRAGDAVLMSADDYDAWQETVYLLRSPENAR RLMEAVARDKAGHSAFTKSV DELREMAGGEE >gi|15610494|ref|NP_217875. 1| protein Rv3358 [Mycobacterium tuberculosis H37Rv] MRSVNFDPDAWEDFLFWLAADRKTARRITRLIGEIQRDPFSGIGKPEPLQGELSGYWSRR IDDEHRLVYRAGDDEVTMLK ARYHY ARYHY >gi|15842953|ref|NP_337990. 11 [Mycobacterium tuberculosis CDC1551] MSISASEARQRLFPLIEQVNTDHQPVRITSRAGDAVLMSADDYDAWQETVYLLRSPENAR RLMEAVARDKAGHSAFTKSV DELREMAGGEE >gi|15842954|ref|NP_337991. 11 [Mycobacterium tuberculosis CDC1551] MRSVNFDPDAWEDFLFWLAADRKTARRITRLIGEIQRDPFSGIGKPEPLQGELSGYWSRR IDDEHRLVYRAGDDEVTMLK ARYHY ARYHY >gi|29829748|ref|NP_824382. 1| protein [Streptomyces avermitilis MA-4680] MSITASEARKALFPLIKKVNDDHEAIEIVSKHGNAVLVSAEDYAALREGSYLLRSPVNAR RLLKAYENALGNINVSEREL IDPDATDPAEGAA >gi|29829747|ref|NP_824381. 1| protein [Streptomyces avermitilis MA-4680] MRLVFEDQGWEDYTSWLKNDRKMLARINRLIEDVKRDPFTGIGKPEPLKYHLPGVWSRRI DDEHRLVYLVTDKEWILAA RYHY RYHY >gi|21220706|ref|NP_626485. 1| [Streptomyces coelicolor A3 (2)] MSITASEARQNLFPLIEQVNEDHAPVHITSRKGNAVLMSEEDFTAWTETVHLLRSPRNAR RLLDSIAEAEAGDATEHDLI DPDAERA >gi|21220707|ref|NP_626486. 11 [Streptomyces coelicolor A3 (2)] MRITFTSHGWEDYVHWAESDRKVTKRINRLIADIARDPFKGVGKPEPLKGDLSGYWSRRI DDTHRLVYKPTDDQLVIVQA

RYHY RYHY >gi|17227668|ref|NP_484216. 1| protein [Nostoc sp. PCC 7120] MYWIKFESTQRELLILMLSNTYTYTQARDRLSELCDKVTSERDFWITRRNAENVALIPVD ELSSLLETAHLLRSPRNAE RLLRALDRAKSGWESQSLDDIRKELGFDQKEESQKPIKRRSSSNSKAKKNSVST >gi|17227667|ref|NP_484215. 1| protein [Nostoc sp. PCC 7120] MFQPEFLEDLEFWVETNQRVALKALDLVKETCRDPFKGKGKPEPLKYLDPDTWSRRLTQE HRIVYLVKDDEINFLQARYH y Y >gi|17229593|ref|NP_486141. 11 protein [Nostoc sp. PCC 7120] MIDPVSATEARAKFQEIINRVEYGKERILIERHGKPWAVIGLDDLKRLETLEDAIDSAQL REAIAQNAGFTTLEAVIAQ HTHE >gi|17229592|ref|NP_486140. 1| protein [Nostoc sp. PCC 7120] MSDRYTLRIARTAEKDLLDLQPKQFKQWSKILSLQGTPRPQDCKALKGYEGGYRVDQGEY RILYTIDDETQLVDVFRVG KRNDDEVYQNL KRNDDEVYQNL >gi|17231900|ref|NP_488448. 1| protein [Nostoc sp. PCC 7120] MRGLYLGVLGSPTKSGRAKMKAIEVTGKIDAQGNLILDQPIQGTTYPDQVRVIVLIPEQE ETEEFDPDDTPVEEIKASLR RALQQAKMGQTRPISELWDRIDAE >gi|17231899|ref|NP_488447. 1| protein [Nostoc sp. PCC 7120] MSYGTELMQSDNTVSIRFSDEFEAELYRLSKRFRKIRSDVQPIIEQLQQGDFVGDRISGF GEEYFVYKVRVRNSNIQKGK SAGYRLIYQVDSPTNIVLLTIYSKSDREDIGANEIRDILADFYGDSG >gi|17231962|ref|NP_488510. 1| protein [Nostoc sp. PCC 7120] MMTLQEIINSIESLPTEDQEYLFEFLRQQRIENRRVEILANSQEVMQALKDGTAKRGSVD DLIADLLGDDDGSCLE >gi|17231963|ref|NP_488511. 1| protein [Nostoc sp. PCC 7120] MMEWWSSGFKRSFKKIIKKKPQLKDQIVKVLRLLADDPFTTSLKSHKLTGDLAGLWSCSV TYDCRIIFTFSEDENLLEM VILLVDIGSHDEVY VILLVDIGSHDEVY >gill72320541refINP-488602. 11 unknown protein [Nostoc sp. PCC 7120] MRYIMQPTETRQALLKAIYEELEQAYDDTLEDVLELLKIRKSEDEEDIQDIYAAKNDTTI SWEQYKQESA >gil7232053) refJNP488601. 1 protein [Nostoc sp. PCC 7120] MIYQIEITTRAAKQLKKLSEDIKLKIEEKIQELSNNPRSNDWKLEGEEDTYRIRVGNYRI LYEIKDDLLIVKWKISHR RDVYRRK RDVYRRK >gil6332147ref NP442875. l) unknown protein [Synechocystis sp. PCC 6803] MMRAFEVMATVKDSKQLLLDSDLHWNTSRVKVIILESDELASKGSEFDPDDTPVEEIKVS LRKALEEYKQGKRIPVENMW EGIDVE >gi|16332148|ref|NP 442876. 1| unknown protein [Synechocystis sp. PCC 6803] MSNNLHLVNIDFTPEYRRSLKYLAKKYRNIRSDVQPIIEALQKGVISGDRLAGFGSDIYV YKLRIKNSNIQKGKSSGYRL IYLLESENSILLLTIYSKAEQEDIAASDINSILGEYSIED IYLLESENSILLLTIYSKAEQEDIAASDINSILGEYSIED >gi|29375140|ref|NP_814293. 11 DNA-damage-inducible protein J, [Enterococcus faecalis V583] MATTKKKPIHVNVDENLKEEAEQLFDDLGLNMTSAITIFLKQSINEQAIPFMINKGNKET LQALKDIKEGNVHGGFSSVE DLMEDLNA >gi|29375141|ref|NP_814294. 1| TIGR00053 [Enterococcus faecalis V583] MLEIFYTNQFKKDFKKAKKQGKNLEKLKEVLVLLQEQQTLPPKYKDHALTGNYIGTRECH IEPDWLLIYKIDGDKLILTL ARIGSHSELFR ARIGSHSELFR >gi|20807339|ref|NP_622510. 1| protein [Thermoanaerobacter tengcongensis] MIKVGDAVMSKRKFFNLKDLASYMISVSDLGRGKASKIIEKVAKKKEHYIVVKNNKPQAV IIPIEEYDELIEAQEDLELL QLAIERTKNLKEGETLPFEEILKEDGLTKEELKKYIDIVEIE >gi|20807340|ref|NP_622511. 1| protein [Thermoanaerobacter tengcongensis] MPLPQSEGGYGKPLGNKQGNNLTGFFKIKYKNIGIRWYTLVRDKKLMNIVAVSPRDDDYC YSVAEKRRRKYGNDLFTKG FEKLESE FEKLESE

>gi20808432) ref) NP623603. l) protein [Thermoanaerobacter tengcongensis] MWRIMDNLLKNKVKEIIENLQEEELAEVIDFIEYLRFKEEKEENEILNDVELIESIKRGL KDIENGDVYDFEDVFKNV >gi) 2080843l) refNP623602. lj [Thermoanaerobacter tengcongensis] MRTCSKMYKVKLAKEAVKFTEKCNSNTKEKIKEAIEKIAQSPYVGKNIKKLKDKFPPLYR YRVGNIRIIYQIQKGEKIIF IVTIGYRGDVYK IVTIGYRGDVYK >gi|20808957|ref|NP_624128. 1| protein [Thermoanaerobacter tengcongensis] MSNSYMVKKLNEVIKSLNERELSEVIDFAEYLKEKKKKELLKRFDEWEKTLDLEEIDIDE EKMLEQLHEDEKDYVTLEET KRILGIEDNEV >gi|20808956|ref|NP_624127. 1| [Thermoanaerobacter tengcongensis] MKFEYRIIVNKKVLKELEKHDRKTVERVIKAIEKLPFEGDVKKLKTSKKEKLYRLRVGDY RIIFEVDNENFVIKVKDFDS RGDVYK RGDVYK >gi) 21284059) ref) NP647147. l) [Staphylococcus aureus subsp. aureus MW2] MIIKNYSYARQNLKALMTKVNDDSDMVTVTSTDDKNVVIMSESDYNSMMETLYLQQNPNN AEHLAQSIADLERGKTITKD IDV >gi21284058jref) NP647146. 1 [Staphylococcus aureus subsp. aureus MW2] MARLNITFSPQAFEDYKYFQQNDKKMVKKINELLKSIDRNGALEGIGKPEKLKSNLTGYY SRRINHEHRLVYTVDDNHIK IASCKYHY IASCKYHY >gi|21284110|ref|NP647198. 11 protein [Staphylococcus aureus subsp. aureus MW2] MIITSPTEARKDFYQLLKNVNNNHEPIYISGNNAENNAVIIGLEDWKSIQETIYLESTGT MDKVREREKDNSGTTNIDDI DWDNL >giJ21284109) ref) NP647197. l) [Staphylococcus aureus subsp. aureus MW2] MSNYTVKIKNSAKSDLKKIKHSYLKKSFLEIVETLKNDPYKITQSFEKLEPKYLERYSRR INHQHRWYTVDDRNKEVLI LSAWSHYD LSAWSHYD >gi) l5927986) ref) NP375519. l) [Staphylococcus aureus subsp. aureus N315] MIIKNYSYARQNLKALMTKVNDDSDMVTVTSTDDKNWIMSESDYNSMMETLYLQQNPNNA EHLAQSIADLERGKTITKD IDV >gi15927985jrefNP375518. lj [Staphylococcus aureus subsp. aureus N315] MARLNITFSPQAFEDYKYFQQNNKKMVKKINELLKSIDRNGALEGIGKPEKLKSNLTGYY SRRINHEHRLVYTVDDNHIK IASCKYHY IASCKYHY >gi|15928036|ref|NP_375569. 1| protein [Staphylococcus aureus subsp. aureus N315] MIITSPTEARKDFYQLLKNVNNNHEPIYISGNNAENNAVIIGLEDWKSIQETIYLESTGT MDKVREREKDNSGTTNIDDI DWDNL >gi|15928035|ref|NP_375568. 1| [Staphylococcus aureus subsp. aureus N315] MSNYTVKIKNSAKSDLRKIKHSYLKKSFLEIVETLKNDPYKITQSFEKLEPKYLERYSRR INHQHRWYTVDDRNKEVLI LSAWSHYD LSAWSHYD >gi|15925398|ref|NP_372932. 1| [Staphylococcus aureus subsp. aureus Mu50] MIIKNYSYARQNLKALMTKVNDDSDMVTVTSTDDKNVVIMSESDYNSMMETLYLQQNPNN AEHLAQSIADLERGKTITKD IDV >gi|15925397|ref|NP_372931. 1| [Staphylococcus aureus subsp. aureus Mu50] MARLNITFSPQAFEDYKYFQQNNKKMVKKINELLKSIDRNGALEGIGKPEKLKSNLTGYY SRRINHEHRLVYTVDDNHIK IASCKYHY IASCKYHY >gi|15925447|ref|NP_372981. 1| protein [Staphylococcus aureus subsp. aureus Mu50] MIITSPTEARKDFYQLLKNVNNNHEPIYISGNNAENNAVIIGLEDWKSIQETIYLESTGT MDKVREREKDNSGTTNIDDI DWDNL >gi) l5925446) ref) NP372980. l) [Staphylococcus aureus subsp. aureus Mu50] MSNYTVKIKNSAKSDLRKIKHSYLKKSFLEIVETLKNDPYKITQSFEKLEPKYLERYSRR INHQHRWYTVDDRNKEVLI LSAWSHYD LSAWSHYD >gi|22538144|ref|NP_688995. 1| [Streptococcus agalactiae 2603V/R] MEAIVYSHFRNNLKDYMKKVNDEFEPLIWNKNPDENIWLSQDSWESLQETIRLMENDYLS HKVINGISQVKEKQVTKH

GLIEVEDV >gi|22538143|ref|NP_688994. 11 [Streptococcus agalactiae 2603V/R] MFNFTEEAWKDYVSWQQEDKKILKRINRLIEDIKRDPFEGIGKPEPLKYHYSGAWSRRIT EEHRLIYMIEDGEIYFLSFR DHYK >gi|22536617|ref|NP_687468. 1| DNA-damage-inducible protein J, [Streptococcus agalac- tiae 2603V/R] MSTVAVRVDDQLKDDATELFQSLGLDMSTAVKMFLIQSVKTQSIPFEIKNKSSVSDEEFQ NLVETKLKGIRVKASDPESV NAFFGDEDFSEYEEYFK >gì|22536618|ref|NP_687469. 1| protein [Streptococcus agalactiae 2603V/R] MSDIEVYSVLVSRIEYSDGTGSKVRPAWVKFNDEVIKTLRFTTKYENKSDNIRSQYLEVI D ------------------------------------------------------------ ------------- >gi|25010542|ref|NP 734937. 11 Unknown [Streptococcus agalactiae NEM316] MSTVAVRVDDQLKDDATELFQSLGLDMSTAVKMFLIQSVKTQSIPFEIKNKSSVSDEEFQ NLVETKLKGIRVKASDSESV NAFFGDEDFSEYEEYFK >gi|25010543|ref|NP_734938. 1| Unknown [Streptococcus agalactiae NEM316] MIDIEVYSVLVSRIEYSDGTGSKVRPAVVVKFNDEVIKTLRLTTKYENKSDNIKSQYLEV IDWAKANLKRRSWIDTIQYY DLEDKGFNIKIIGRLSDRDIERLKDFLRAKEV DLEDKGFNIKIIGRLSDRDIERLKDFLRAKEV >gi|24379347|ref|NP_721302. 1| possible DNA-damage-inducible protein [Streptococcus mutans UA159] MWKNKANINIKIDLEDKAAADAIFAHMGLTTSAAVNMFIKRVIDDQALPFTPRVKNTLDI ALEQAKNDDVETFDSFDDW KSEMSAYAKD >gi|24379348|ref|NP_721303. 1| [Streptococcus mutans UA159] MLKIKQTRQFKKSLKKWKQGKDINKLFAIVELLCQKSELPLALRNHELKGRWRGIRELHI ESDWLLAYQVLDDELVLLL IDTGSHAQMLGM IDTGSHAQMLGM >gi|15900209|ref|NP_344813. 11 [Streptococcus pneumoniae TIGR4] MSKMSISIRLDSEVKEQAQQVFSNLGMDMTTAINIFLRQAIQYQGLPFDVRLDENRKLLQ ALTDLDQNRNMSQSFESVSD LMEDLRA >gi|15900210|ref|NP_344814. 11 [Streptococcus pneumoniae TIGR4] MLKIRYHKQFKKDFKLAMKRGLKAELLEEVLNFLVQEKEHPARNRDHSLTASKHFQGVRE CHTQPDWLLVYKVDKSELIL NLLRTGSHSDLF NLLRTGSHSDLF >giI15901086refNP_345690. 1 conserved domain protein [Streptococcus pneumoniae TIGR4] MTEHLKSNTMVLPLKKGAQKMTTITLKVSEADKTFMKAMAKFEGVSLSELIRTKTLEALE DEYDARVADLAYQEYLEDLE KGVEPITWEEMMHDLGLKDE >gi|15901085|ref|NP_345689. 1| [Streptococcus pneumoniae TIGR4] MYKLVPTRRFIKQLKKLDRYTQKLITNYLQTNVLEDPRRHGKALVGNRVGQWRYRIGNYR VIVQIVDDELWATLEVGHR RDIY RDIY >gi|15901573|ref|NP_346177. 1| [Streptococcus pneumoniae TIGR4] MEAVLYSTFRNHLKDYMKKVNDEFEPLTVVNKNPDEDIVVLSKSEWDSIQETLRIAQNKE LSDKVLRGMAQVRAGSTQVH VIEE >gi|15901572|ref|NP_346176. 1| [Streptococcus pneumoniae TIGR4] MLLKFTEDAWADYCYWQNQDKKTLKRINKLIKDIQRDPFTGIGKPEPLKYDYQGAWSRRI DAENRLIYMMDGDSVAFLSF KDHY KDHY >gi|15902296|ref|NP_357846. 1| protein [Streptococcus pneumoniae R6] MSKMSMSIRLDSEVKEQAQQVFSNLGMDMTTAINIFLRQAIQYQGLPFDVRLDENRKLLQ VLTDLDQNRNMSQSFESVSD LMEDLRA >gi|15902297|ref|NP_357847. 1| [Streptococcus pneumoniae R6] MLKIRYHKQFKKDFKLAMKRGLKAELLEEVLNFLVQEKEHPARYRDHSLTASKHFQGVRE CHTQPDWLLVYKVDKSELIL NLLRTGSHSDLF NLLRTGSHSDLF >gi|15903147|ref|NP_358697. 1| protein [Streptococcus pneumoniae R6] MTEHLKSNTMVLPLKKGAQKMTTITLKVSEADKTFMKAMAKFEGVSLSELIRTKTLEALE DEYDARVADLAYQEYLEDLE

KGVEPITWEEMMHDLGLKDE >gi|15903146|ref|NP_358696. 1| protein [Streptococcus pneumoniae R6] MNNLYKLVPTRRFIKQLKKLDRYTQKLITNYLQTNVLEDPRRHGKALVGNRVGQWRYRIG NYRVIVQIVDDELVVATLEV GHRRDIY GHRRDIY >gi|15903628|ref|NP_359178. 1| [Streptococcus pneumoniae R6] MYNSGKELKRGMVMEAVLYSTFRNHLKDYMKKVNDEFEPLTWNKNPDEDIWLSKSEWDSI QETLRIAQNKELSDKVLR GMAQVRAGSTQVHVIEE >gi|15903627|ref|NP_359177. 11 [Streptococcus pneumoniae R6] MLLKFTEDAWADYCYWQNQDKKTLKRINKLIKDIQRDPFTGIGKPEPLKYDYQGAWSRRI DAENRLIYMMDGDSVAFLSF KDHY >gi|19703555|ref|NP 603117. 1| Transcriptional regulator, COPG family [Fusobacterium nucleatum subsp. nucleatum ATCC 25586] MGTTATLRLDETEKAIIQDYASSKGMTMSEFVKRWLDYIEDEYDLKIYKEYLKEKENGTL KTYSHKEVWGE >gi|19703556|ref|NP_603118. 1| Plasmid addiction system poison protein [Fusobacterium nucleatum subsp. nucleatum ATCC 25586] MKYDVEYSKTAMNTIKKMDSSTSKLIRTWIEKNLINTENPRIKGKALTGDLKGLWRYRIG DYRILAEIQDDKIVILILDI GHRSKIYL GHRSKIYL >gi|19703831|ref|NP 603393. 1| unknown [Fusobacterium nucleatum subsp. nucleatum ATCC 25586] MSALSIRLNDDEKKIINAYAKFYNKTITQVVKEAILEKIENEFDLNELNKAIEEYEKNPV SYSSDEVWKMLGI >gi|19703832|ref|NP_603394. 1| Plasmid addiction system poison protein [Fusobacterium nucleatum subsp. nucleatum ATCC 25586] MKKYEVKFSEAAIKELKKLDKPTATMIKLWVIQNLENTINPRQHGKSLTANYSGKWRYRV GNYRLLAEIYDDEILILIFK VAHRSIVYKK >gi|19704434|ref|NP 603996. 1| unknown [Fusobacterium nucleatum subsp. nucleatum ATCC 25586] MSWSIRFNDDEEEILKNYVKSKGLNLSQYIKNIIFEKIEEEYDLKSVQEYLKAKSEGTLN LIPFEEAIKEWDIE >gi|19704435|ref|NP_603997. 1| Plasmid addiction system poison protein [Fusobacterium nucleatum subsp. nucleatum ATCC 25586] MGYRVMIPDKVNKKILKFDRNTRKLLYDYINKNLKDTDDPRLHGKALTGNLKGLWRYRIM DYRLIVDIQDEQLIIVAVDF NHRRKIYL NHRRKIYL >gi|32472872|ref|NP_865866. 1| protein [Pirellula sp.] MRRESDRRPDCSDDGASFHRRTSFPKKVLPVPKAFLIGKTLAKHANSAQNGVSFKLPLAT IAILLREFPYWGIHKWSETA NMGGQRRLQ >gi|32472873|ref|NP_865867. 1| [Pirellula sp.] MRLATPLTVCPMAQAGMRSSTACTFAKRSNPVWPPQNHLGWSALTPYANNGTRLAMQVSW TEYAVSDLLAIRDYIGRDSD KFADLIFERIVEQTERLLEYPDAGSIVPEFGREDVSEIQVNSYRWHQIFDDEVRVLTVSH ATAPSAVLVGDGP ------------------------------------------------------------ ------------- >gi|16125056|ref|NP_419620. 1| protein [Caulobacter crescentus CB15] MADGFDIHIDQEQAARLKWADRLGMSVSEYAVALIDAGLTGAAPKAIDPDPAIDEAIADA IERGDEPAISRDEFRAHIR RVTAGLG >gi|16125055|ref|NP_419619. 1| [Caulobacter crescentus CB15] MTFTVLVSVRAKRDFNRLIVWLVERDPRAAARLGPLLEAALDSLTEAPSRGRSVGPTTRE ISIPFGQSAYVIRYRLLGSS VHVTRIWHGLEQR >gi|16126753|ref|NP_421317. 1| protein [Caulobacter crescentus CB15] MAICYARFMVPEPSIFEIDAEAEEAADAEGMADIAAGRWPHEEVSAWLDTWGTPEEKPAP ETWRK >gi|16126752|ref|NP_421316. 1| [Caulobacter crescentus CB15] MAQWWTWRALADLTAIRDYIGQFSPLAAQRMALRLKTAADSLAEYPERGRLATATLRELW VPPYVIRYYVADGLVHIV RIRHAARL >gi|16127111|ref|NP_421675. 11 protein [Caulobacter crescentus CB15] MSGVIAPDRVDDKRRMEHSQNMALTITIPAELASRLRASAEAEGKDVDAYAIDALHVMSD EDWGYTDDDAYWRELRAHSD

EVRRDGGIPLEDVKRWVASWDTENELPPPEPRIKARG >gi16127112refNP_421676. 1I protein [Caulobacter crescentus CB15] MKSVELGPRARRDLTKLRRWLLNRAPSAADRAIDLILSRAEQLAQHSDLGRRKSQNMREL YVSFGAHGYVLQYRVYPDAV VIARIRHSLERR >gi|15888018|ref|NP_353699. 1| AGR_C_1208p [Agrobacterium tumefaciens] MSKQTAIRLPDETYERLKALSERTGRTSAYYIREAIEKHIEDMEDLYLAEEATRRIQRGE SKIISAEEFWRDLDN >gi|15888017|ref|NP_353698. 1| AGR_C_1206p [Agrobacterium tumefaciens] MIWTIEYHTLVQKEMRKINPEVRRRIRSFLHERLAALDDPRQIGATLQGSELGNFWRYRV GDYRIICDIQDQKLWLWE IGHRREIYR IGHRREIYR >gi 15888153ref NP353834. 1 AGRC1484p [Agrobacterium tumefaciens] MANVEKISVSMTPQHAEILRDAVESGAYASSSEVIREAMRDWSAKWVQRRNDITKLRALW SEGKASGNSTEVDFDETLNE ARAELASLKNRDH >gil15888152|ref|NP_353833. 1| AGR_C_1483p [Agrobacterium tumefaciens] MTTKLVWTPRARSDVKKIYVDIGKSQPLAAERYFARFRAKAESLIDHPHLGERHPEIFPS ARMLVEAPYVILYETVPDTD DDEIRCVEIVRVNDGRRDLRTLF >gi|15888172|ref|NP_353853. 11 AGR_C_1520p [Agrobacterium tumefaciens] MIWCSADVKPVYLPQGPRLQGFAFDLSLPMTDLMHRNCNAGRRSMKTATIPSLRVTADFR EAAESVLKDGETLSAFMEEA VRKQVEIRKSQAEFIKQGLAAREESKRTGVYHKAEDVLAELKAMLDEKLAEDNDK >gi|15888171|ref|NP_353852. 11 AGR_C_1518p [Agrobacterium tumefaciens] MTFQVFLADRARDNITRLYAHLLRQDKYAAKRAYRAIEKGIAALADFPLSCRKVDAENPF LREFLIPFGSSGYVVLFEIE SAEKVTILAIRHQREDDYH SAEKVTILAIRHQREDDYH >gi|15888274|ref|NP_353955. 1| AGR_C_1704p [Agrobacterium tumefaciens] MTANAYVRARIDQTLKDDATAVLDRLGLTVSDVMRMMLTRIAREKALPIELTQPNAETLA AIEEARAIAAAGRNRFGTSE ALFEALDAGKR >gi|15888273|ref|NP_353954. 1| AGR_C_1701p [Agrobacterium tumefaciens] MTNKKDHGKDAALKRATLPRRSDFTKQFIKDWQRLNNSGRYDMVRLKEIMLLLIANGAPL PTQFRDHELTGDWRDHRECH VGGDFLLIYTVDEKQNLLIFTRAGTHAELFR VGGDFLLIYTVDEKQNLLIFTRAGTHAELFR >gi|15889087|ref|NP_354768. 1| AGR_C_3279p [Agrobacterium tumefaciens] MKGLSKALDSFLHSHVRMKCHKLDEPIWFTNNHSEPGKVAIMTAFTVRLPDEVAEKLDQL AEKLDRSRSYMAVQAIEDFV AREEWQLAEIEAGLAEADRGEFGTPEDLANIVGRYVKTARPL >gi|15889086|ref|NP_354767. 1| AGR_C_3278p [Agrobacterium tumefaciens] MSDRRIRWTLRALRRLDEIGAHIEQDNPAAAARVISRIVSAADMLVEQPAIGRVGRIKGT REAVLSDISYIIAYRVGRDI EILTIIHTSRRWPSAL >gi) l5889306refNP354987. 1 AGRC3659p [Agrobacterium tumefaciens] MLGGRHGGRGESSGLSCYRSHRCILTFGVWSVHKSVHICGRAILMANVRFTEFRQNFATH FDRVLETRAPLLVTRQGKEA VWLAEGEYESMQETLHLLSNPANASRLRASMGELERGDTIERDPTEE >gi|15889305|ref|NP_354986. 11 AGR_C_3658p [Agrobacterium tumefaciens] MKLVWTLSSWDDYEFWQRTDARMVEKINDLIRNAKRTPFAGLGKPEPLKGDMAGYWSRRI TAEHRFVYRVSGSGSEQRLE VIQCRFHYQ >gi15890524ref) NP356196. 1 AGRL816p [Agrobacterium tumefaciens] MKSTIELSDDIKRRLDILAERSNSTPSRITEDALSHGRSLAWQEKWTSGVRAGLAEADAG EFVTEEEINDVLNKYAKA >gi|15890523|ref|NP_356195. 11 AGR_L_815p [Agrobacterium tumefaciens] MRLIWTRRYLRELDAIGVYIAERNPRAAAKWRAIHQTTARLLSDNPHLGRSGEIEGTREL WPGLPYIVAYRVTEEQVD IVFVQHAAREWPDDA >gi|17934585|ref|NP_531375. 1| [Agrobacterium tumefaciens str. C58 (U. Washington)] MSKQTAIRLPDETYERLKALSERTGRTSAYYIREAIEKHIEDMEDLYLAEEATRRIQRGE SKIISAEEFWRDLDN >gi|17934584|ref|NP_531374. 1| [Agrobacterium tumefaciens str. C58 (U. Washington)] MIWTIEYHTLVQKEMRKINPEVRRRIRSFLHERLAALDDPRQIGATLQGSELGNFWRYRV GDYRIICDIQDQKLWLWE IGHRREIYR

------------------------------------------------------------ ------------- >gi|17934843|ref|NP_531633. 1| [Agrobacterium tumefaciens str. C58 (U. Washington)] MTANAYVRARIDQTLKDDATAVLDRLGLTVSDVMRMMLTRIAREKALPIELTQPNAETLA AIEEARAIAAAGRNRFGTSE ALFEALDAGKR >gi|17934842|ref|NP_531632. 11 [Agrobacterium tumefaciens str. C58 (U. Washington)] MKRATLPRRSDFTKQFIKDWQRLNNSGRYDMVRLKEIMLLLIANGAPLPTQFRDHELTGD WRDHRECHVGGDFLLIYTVD EKQNLLIFTRAGTHAELFR >gi|17934986|ref|NP_531776. 11 protein [Agrobacterium tumefaciens str. C58 (U. Wash- ington)] MPEIHLSEQDEKFIEEQVAAGIYSDADAVIHASLQLLSSDEGKRAALKLLIQEGIDDAEA GRVHRYASQNDFLSDIKRVS AQQKTGTDH >gi17934985IrefNP_531775. 1 protein [Agrobacterium tumefaciens str. C58 (U. Wash- ington)] MKIRTPIWTTRARRDLAEDHAYIETENPVAADRLVLDIYNKIESIAAIGLTGVSRHGYGT GLRSIAYRDRVIFFRVNNGE LTVMRVLHGHQDISADDFKQEEN LTVMRVLHGHQDISADDFKQEEN >gi|17935676|ref|NP_532466. 1| [Agrobacterium tumefaciens str. C58 (U. Washington)] MTAFTVRLPDEVAEKLDQLAEKLDRSRSYMAVQAIEDFVAREEWQLAEIEAGLAEADRGE FGTPEDLANIVGRYVKTARP L >gi|17935675|ref|NP_532465. 1| [Agrobacterium tumefaciens str. C58 (U. Washington)] MSDRRIRWTLRALRRLDEIGAHIEQDNPAAAARVISRIVSAADMLVEQPAIGRVGRIKGT REAVLSDISYIIAYRVGRDI EILTIIHTSRRWPSAL >gi|17935904|ref {NP_532694. 1| [Agrobacterium tumefaciens str. C58 (U. Washington)] MANVRFTEFRQNFATHFDRVLETRAPLLVTRQGKEAWVLAEGEYESMQETLHLLSNPANA SRLRASMGELERGDTIERD PTEE >gi|17935903|ref|NP_532693. 1| [Agrobacterium tumefaciens str. C58 (U. Washington)] MKLVWTLSSWDDYEFWQRTDARMVEKINDLIRNAKRTPFAGLGKPEPLKGDMAGYWSRRI TAEHRFVYRVSGSGSEQRLE VIQCRFHYQ VIQCRFHYQ >gi|17938149|ref|NP 534938. 1| [Agrobacterium tumefaciens str. C58 (U. Washington)] MELSDDIKRRLDILAERSNSTPSRIIEDALSHGRSLAWQEKWTSGVRAGLAEADAGEFVT EEEINDVLNKYAKA >gi17938150IrefINP_534939. 1 [Agrobacterium tumefaciens str. C58 (U. Washington)] MRLIWTRRYLRELDAIGVYIAERNPRAAAKWRAIHQTTARLLSDNPHLGRSGEIEGTREL WPGLPYIVAYRVTEEQVD IVFVQHAAREWPDDA IVFVQHAAREWPDDA >gi|17987808|ref|NP_540442. 11 Helix-turn-helix protein, copG family [Brucella melit- ensis] MKNQHLSDPITMRIPRDLLAEIEEIASLTERSRSWVIVRAMKAYLAAEGREIRDIAKARC AIENGEGIDLDTVIEEAEAI IKGAAA >gi|17987809|ref|NP_540443. 11 Cytosolic Protein [Brucella melitensis] MKVIVSPAARDYIKSEIAYLKLRSPSAAVQLSEDLKRLKRDLGRFSQMGHFTEELPVPGI RRFVMGAYLIDYEIRADAIL IFAIRHGRERPPILPPDEDFDFEQL IFAIRHGRERPPILPPDEDFDFEQIj >gi|23501312|ref|NP_697439. 11 [Brucella suis 1330] MKNQHLSDPITMRIPRDLLAEIEEIASLTERSRSWVIVRAMKAYLAAEGREIRDIAKARC AIENGEGIDLDTVIEEAEAI IKGAAA >gi|23501311|ref|NP_697438. 1| [Brucella suis 1330] MKVIVSPAARDYIKSEIAYLKLRSPSAAVQLSEDLKRLKRDLGRFSQMGHFTEELPVPGI RRFVMGAYLIDYEIRADAIL IFAIRHGRERPPILPPDEDFDFEQS >gi|15966432|ref|NP_386785. 1| [Sinorhizobium meliloti] MQTEKLSISLPVDMARMVRRRVEDGAYASNSEVIREALRLWQQREQERGHRLDAIRASLD AAANDPARHGSAEVSAHFDR LLTEAEKTAKS >gi|15966431|ref|NP_386784. 11 [Sinorhizobium meliloti] MSRELVFTPAALADLEETFWFVAADNPRRARSYVAEIEQACRNLCETPLMGRGRPDLRPN LFIFPLWRRVLIAYELPDNR VDILRVFSGGQDYEAIMSGE

--------------------------------------------------------- 7--------------- >gi|15892213|ref|NP_359927. 1| unknown [Rickettsia conorii] MTKRTVYSTLLILSLTNYKEKIMEIYNTSEARSKLYKLIDYVSDVHKPVYIKGKRNNVVI ISEEDYRNMEETLYLLSIPN MRKSIIEGRAEPIAKCSDKLNW >gi|15892214|refXNP_359928. 1| unknown [Rickettsia conorii] MYIIRYTIQVQKDAKKIVQAGLKNKVEVLLNIVSTDPWKIYPPYEKLVGDFSGCYSRRIN IQHRLVYEVYKQEKVVKILR MYTYYE >gi|17547944|ref|NP_521346. 1| [Ralstonia solanacearum] MPTSVALGNHFETFIRDQVQSGRFNNVSEVVRAGLRLLEESEQRRQLELQALRAEIAAGK ASGPAKPADEVFSRLEAKYS AQARRKQN >gi|17547943|ref|NP_521345. 11 [Ralstonia solanacearum] MRLAITPLAEQDLESIADYIAQDNPARAVTFVRDLREQCQRLVMNPPGYRLRPELGDDIR SCAYGRYVIFFVAAPDEVIV IRILHGARDLPAVFHADEP IRILHGARDLPAVFHADEP >gi|17547995|ref|NP_521397. 1| [Ralstonia solanacearum] MNAPTGTNVQLIHGPDGAPAFWIPYAEYIAGRMQDRSLIPHAVIERTVEGATPVRAWREH LGLTQAEVAGRLGISQPAY AQQESSDRLRKASRDRIAAALGILPAQLDF >gi|17547996|ref|NP_521398. 11 [Ralstonia solanacearum] MNAIHWTAWAARQLRKLDRQHQRVLVEAVGQLEAMPHCRQVRALREHRYGYRLRVGDYRV LSDWDDGIRIVDIQEVSKRD ERTYRH ERTYRH >gi|30248490|ref|NP 840560. 1| Helix-turn-helix protein, CopG family [Nitrosomonas europaea ATCC 19718] MAQITARLPDDLVSSLDAAAARLRRSRAEWRQAVEYYLEDFEDISQAIDILRDPADPILD WEEVKRDLLHLD >gi|30248491|ref|NP_840561. 1| Protein of unknown function DUF79 [Nitrosomonas eu- ropaea ATCC 19718] MIYSISIRQSAVKSLEKIPGPDRLRIIKAIDLLKEHPGAGSILKGEFSGLRRIRVGMYRW YEIQDNLLTILWRINHRR DIYR >gi|30248712|ref|NP_840782. 1| [Nitrosomonas europaea ATCC 19718] MRYSTQIRPISYLKANAAEVLAYLTENREPLIITQNGEAKAVIQDIASFEETQETLALLK ILALGNAEIEAGEVQPVHEV IAGLRTRQTIK >gi|30248711|ref|NP_840781. 1| [Nitrosomonas europaea ATCC 19718] MAIRQYEVLFTRGAEQDLELIYDYIVESDCKANADSVLDRLLEWENLATFPSRGTWPKEL VAVGIREYRQAIFKPYRVI YRVIEQKVYIYLIADGRRDMQSLLMHRLLGK YRVIEQKVYIYLIADGRRDMQSLLMHRLLGK >gi|30248721|ref|NP_840791. 1| DUF172 [Nitrosomonas europaea ATCC 19718] MAECNVQINVQLENLMDAITYSTARAKLADTMNRVCDNHEPIIITRNGEQSWMMSLDDFK ALEETSYLLRSPKNAKRLL ESIAALESGRGETRSLAE >gi|30248722|ref|NP_840792. 1| [Nitrosomonas europaea ATCC 19718] MKLVFSEQAWEDYLYWQKTDRKTVQRIDTLVKEITRTPHEGTGKPEPLKHALSGYWSRRI NNEHRIVYKIADDSLFIAQL RYHY RYHY >gì|30249325|ref|NP_841395. 1| DUF172 [Nitrosomonas europaea ATCC 19718] MYLFYTCTIYCANEVAMKVVTYSHARNALKSILDDVIQDADVIVISRRDAEGDAWMSLDS YNSIMETLHLTSNPANAAA LAKAIAQDKAGQAQDHPLLSAD >gi|30249324|ref|NP_841394. 1| [Nitrosomonas europaea ATCC 19718] MRAIRFVPDAWEAYLYWQDQDKKTLRRLNSLITAASRDPFVGIGKPEPLRGELSGYWSRR IDETNRLVYRVTDVELVIIA CRFHYE CRFHYE >gi|30249531|ref|NP_841601. 11 [Nitrosomonas europaea ATCC 19718] MHQILASFSASISELKKNPTALLRKAEGETIAILNHNLPTAYLVPAEVYELLMEKLEDYE LGEIVKARQAEKHLAIEVSL DDL >gi|30249532|ref|NP_841602. 1| Protein of unknown function DUF79 [Nitrosomonas eu- ropaea ATCC 19718] MTYKLKFLPSAKKEWDKLDSSIKTQFKNKLKKCLENPHIQPNKLRGFDNAYKIKLRSAGY RLVYEINNQEWVFVIAVGK RENNKIYDKAINRTKT

------------------------------------------------------------ ------------- >gi|30249547|ref|NP_841617. 1| [Nitrosomonas europaea ATCC 19718] MEAVMTIKFSEDVIPLADLKVNPGRWSRVKETRRPVLLTSRGRGVAWQDLDEYEKSQEEL AFVKAVAQGLMDIKEGNT MSLSEAKKRLGIE >gi|30249546|ref|NP_841616. 1| [Nitrosomonas europaea ATCC 19718] MKVSISNSAFNDLETMISYYTAEGVPDVGFKFAQEIIEHIQILADHPDMGRIVPEFQLPH IREIIFAPFRVVYLREKGAI KVIRVWRSERPLVLPTET KVIRVWRSERPLVLPTET >gi|30249552|ref|NP_841622. 11 [Nitrosomonas europaea ATCC 19718] MPNKILTEIAASISELKANPMKWASGKGMPIAVLNHNEPAFYCVPAAAYEAMMELLDDIE LLKIVKERMDEPSVKVSLD DL >gi|30249553|ref|NP_841623. 1| protein [Nitrosomonas europaea ATCC 19718] MTYKLEFKKSALKEWEKLGHTIKEQFKKKLKERLENPHVHSAALPGAKNIYKIKLRQPGY RLVYSVEDQTITVTVIAIGK RDRNEIYDIALSRLHDKS RDRNEIYDIALSRLHDKS >gi30249567ref] NP841637. 1 protein [Nitrosomonas europaea ATCC 19718] MNTINANDLKTRGIAAIEAQLEEQPEAIIAVRGKDRYVVMQLEHYYYLRECELTAALAET RADLAAGRCEQESPEAHLAR LDTLK >gi|30249568|ref|NP_841638. 1| [Nitrosomonas europaea ATCC 19718] MGYSLIFTDAYNQRAARWLRRHPDLRTQYLRTLQILQTNPYHPSLRLHVLSGKLQGIYAI SINLSYRITLEFLIEDKQII PINIGSHDWY >gi|15645511|ref|NP_207686. 1| protein [Helicobacter pylori 26695] MPNTTNKDYTKYSQRQLFSFLNSIKTKQKRALEKLKEIQAQKQRIKKALQFKALNLTENG YTIEEEREILARAKDTKNRL CFKSIEDFKKHCENL >gi|15645510|ref|NP_207685. 1| [Helicobacter pylori 26695] MLTIETSKKFDKDLKILVKNGFDLKLLYKVVGNLATEQPLAPKYKDHPLKGGLKDFRECH LKPDLLLVYQIKKQENTLFL VRLGSHSELF VRLGSHSELF >gi|15645513|ref|NP_207688. 1| protein [Helicobacter pylori 26695] MPNTTAKKDYTKYSKKQLFNLIHQLERKIKKMQNDRISFKEKMAKELEKRDQNFKDKIDA LNELLQKISQAFDDKRDCCL GHEIPNIETQQAMRDVGNKETDLIVEDFSSYSNERKRALGVEAQS >gi|15645512|ref|NP_207687. 11 [Helicobacter pylori 26695] MLKLNLKKSFQKDFDKLLLNGFDDSVLNEVILTLRKKEPLDPQFQDHALKGKWKPFRECH IKPDVLLVYLVKDDELILLR LGSHSELF LGSHSELF >gi|15611899|ref|NP_223550. 11 [Helicobacter pylori J99] MPNTTNKDYTKYSQKQLFNFLNSIKAKQKRALEKLKEIQTQKQRIKKALQFKALHLTENG YTIEEEREILARAKDTKNRL CFKSIEDFKKHCENL >gi|15611898|ref|NP_223549. 1| [Helicobacter pylori J99] MLTIETSKKFDKDLKILVKNGFDLKLLYKVWGNLATEQPLEPKYKDHPLKGALKDFRECH LKPDLLLVYQIKKQENTLFL VRLGSHSELF VRLGSHSELF >gi|26248392|ref|NP_754432. 11 protein yefM [Escherichia coli CFT073] MNCTKEEIYMRTISYSEARQNLSATMMKAVEDHAPILITRQNGEACVLMSLEEYNSLEET AYLLRSPANARRLMDSIDSL KSGKGTEKDIIE >gi|26248391|ref|NP_754431. 1| protein [Escherichia coli CFT073] MKLIWSEESWDDYLYWQETDKRIVKKINEIIKDTRRTPFEGKGKPEPLKHNLSGFWSRRI TEEHRLVYAVTDDSLLIAAC RYHY >gi|16129523|ref|NP_416082. 1| negative regulator of translation [Escherichia coli K12] MGSINLRIDDELKARSYAALEKMGVTPSEALRLMLEYIADNERLPFKQTLLSDEDAELVE IVKERLRNPKPVRVTLDEL >gi|16129522|ref|NP_416081. 11 orf, protein [Escherichia coli K12] MAYFLDFDERALKEWRKLGSTVREQLKKKLVEVLESPRIEANKLRGMPDCYKIKLRSSGY RLVYQVIDEKVVFVISVGK RERSEVYSEAVKRIL RERSEVYSEAVKRIL

>gi|16128212|ref|NP_414761. 11 damage-inducible protein J [Escherichia coli K12] MAANAFVRARIDEDLKNQAADVLAGMGLTISDLVRITLTKVAREKALPFDLREPNQLTIQ SIKNSEAGIDVHKAKDADDL FDKLGI >gi|16128211|ref|NP_414760. 1| orf, protein [Escherichia coli K12] MIQRDIEYSGQYSKDVKLAQKRHKDMNKLKYLMTLLINNTLPLPAVYKDHPLQGSWKGYR DAHVEPDWILIYKLTDKLLR FERTGTHAALFG >gi|15829507|ref|NP_308280. 1| damage-inducible protein DinT [Escherichia coli 0157 : H7] MAANAFVRARIDEDLKNQAADVLAGMGLTISDLVRITLTKVAREKALPFDLREPNQLTIQ SIKNSEAGVDVHKAKDADDL FDKLGV >gi|15829506|ref|NP_308279. 11 protein [Escherichia coli 0157 : H7] MNSGQFSKDVKLAQKRHKDMNKLKYLMTLLINNTLPLPAVYKDHPLQGSWKGYRDAHVEP DWILIYKLTDKLLRFERTGT HAALFG HAALFG >gi|24112921|ref|NP_707431. 1| negative regulator of translation [Shigella flexneri 2a str. 301] MGSINLRIDDELKARSYAALEKMGVTPSEALRLMLEYIADNERLPFKQTLLSDEDAELVE IVKERLRNPKPVRVTLDEL >giI24112920refNP_707430. 1 orf, [Shigella flexneri 2a str. 301] MAYFLDFDERALKEWRKLGSTVREQLKKKLVEVLESPRIEANKLRGMPDCYKIKLRSSGY RLVYQVIDEKVVVFVISVGK RERSEVYSEAVKRIL RERSEVYSEAVKRIL >gi|24113402|ref|NP_707912. 11 orf, [Shigella flexneri 2a str. 301] MRTISYSEARQNLSATMMKAVEDHAPILITRQNGEACVLMSLEEYNSLEETAYLLRSPAN ARRLMDSIDSLKSGKGTEKD IIEWVMLPTY >gi24113399Jref) NP707909. lj orf, [Shigella flexneri 2a str. 301] MKLIWSEESWDDYLYWQETDKRIVKKINELIKDTRRTPFEGKGKPEPLKHNLSGFWSRRI TEEHRLVYAVTDDSLLIAAC RYHY RYHY >gi|30063051|ref|NP_837222. 11 negative regulator of translation [Shigella flexneri 2a str. 2457T] MGSINLRIDDELKARSYAALEKMGVTPSEALRLMLEYIADNERLPFKQTLLSDEDAELVE IVKERLRNPKPVRVTLDEL >gi|30063050|reftNP_837221. 11 protein [Shigella flexneri 2a str. 2457T] MAYFLDFDERALKEWRKLGSTVREQLKKKLVEVLESPRIEANKLRGMPDCYKIKLRSSGY RLVYQVIDEKVVVFVISVGK RERSEVYSEAVKRIL >gi|29653635|ref|NP_819327. 1| protein [Coxiella burnetii RSA 493] MIVYSFFKEIRVGKKEPEKSRWEIKYWCNDKDDGTVEKWLDSLTQEQLKSVASEWHY >gi|29653636|ref|NP_819328. 1| conserved domain protein [Coxiella burnetii RSA 493] MALLELCGNRLRLPHSSSLKKGLFELRERKFGYRIYYAFLPNKTVILLHAGDKKSQKRDI KTARQRLPEFTDAEE ------------------------------------------------------------ ------------- >gi|29655274|ref|NP_820966. 11 [Coxiella burnetii RSA 493] MNVWTFSELRAQLKKILDLSADQHEPWVKRPNKETMVILSLRDFEALKETAYLLSNEANA ARLRQSIRSLKQGKAQKKK LMED >gi|29655275|ref|NP_820967. 1| [Coxiella burnetii RSA 493] MQISFTPEAWEDYLYWQKFDKKMLRRINELIKDAMHEPFSGKGKPEPLKFELQGYWSRRL DQEHRLVYKVLDDSLMIIAA RFHYNRLNSKN >gi|24376115|ref|NP_720158. 1| [Shewanella oneidensis MR-1] MKVELVTSLKRQATKILADLHETKEPVLITEHGKPSAYLIDVEDYEFMQNRLAILEGIAR GERALADGKVVSHQDAKDRM SKWLK >gi|24376114|ref|NP_720157. 11 [Shewanella oneidensis MR-1] MAEIIWTEPALADLNDIAEYIALENIVAAKQLVQMVFAKVERLVDFPDSGRIPPELERLN YREVWNPCRVFYKYGDEKV RILFVMRAERDLRRFMLTRAC RILFVMRAERDLRRFMLTRAC >gi|15601089|ref|NP_232720. 11 DNA-damage-inducible protein J [Vibrio cholerae] MRTEMLSTRIDHDTKIAFTNVCDEMGLSTSQAIKLFAKAVINHGGIPFELRVPQPNEVTA SAIQELVEGKGHKAESVEAM LNELTEGKVKHV

>gi|15601088|reflNP_232719. 1| [Vibrio cholerae] MSLLKAKLSMYKLEYSTQFKKDFKKITKMPISDIIEVGNVISKLQRGEKLEPKNVDHPLT GNWVGFRDCHIKPDLVLIYR VFNDQLQLARIGSHSDLF VFNDQLQLARIGSHSDLF >gi|15601114|ref|NP_232745. 11 relB protein [Vibrio cholerae] MTVPLEAFVSCPTPTPVLTFVHTTKELTMDTRIQFRVDEETKRLAQQMAESQGRTLSDAC RELTEQLAEQQRKALSHDAW LTEQVNQAFEKFDSGKAVFIEHDIAKARMAERKAKIRNRGHA >gi|15601113|ref|NP_232744. 1| [Vibrio cholerae] MIFWEEASLNDREKIFEFLYDFNPAAAKKTDELIEAKVENLLEQPLIGVQRDGIRGRLLI IPEISMIVSYWVDGSKIRIM RVLHQKQKFPND >gi|15601185|ref|NP_232816. 1| [Vibrio cholerae] MEFVMSRIHLDQDIQPLSEFRAGVASFIKQINETRRPLVITQRGKGVAWLDVAEYEAMQE KIELLEEMRTAEAQLAAGL GISNEDARSQVLGRIIK >gi|15601186|ref|NP_232817. 11 [Vibrio cholerae] MKVVWSPLALQKLGDAAEFIALDNPSAAEKWVNEVFDKTELLGSMPEMGRMVPEMPHTNY REIIFGHYRIIYSLSHEIRV LTLRQEQTVNPPHNKRLKRDCQRVAFPVPLSRGGCSCCV LTLRQEQTVNPPHNKRLKRDCQRVAFPVPLSRGGCSCCV >gi|15601208|ref|NP_232839. 1| [Vibrio cholerae] MTTRILADVAASITEFKANPMKVATSAFGAPVAVLNRNEPAFYCVPASTYEIMMDKLEDL ELLAIAKERLSEDSVSVNID DL >gi|15601207|ref|NP_232838. 11 relE protein [Vibrio cholerae] MTYKLEFKKSALKEWKKLAVPLQQQFKKKLIERLENPHVPSAKLSGAENIYKIKLRQSGY RLVYQVENDIIWTVLAVGK RERSEVYTKALQRLDD RERSEVYTKALQRLDD >gi|15601238|ref|NP_232869. 1| [Vibrio cholerae] MMLIWCFMRQVLANCSASISELKKNPTALLNEADGSAIAILNHNKPAAYLVPAETYEYLI DMLDDYELSQIVDSRRADLA QAVEVNIDDL >gi|15601239|ref|NP_232870. 1| [Vibrio cholerae] MMTYKLKFLPAAQKEWSKLAPTIQSQFKKKLKERLENPHVPSAKLRGYDAVYKIKLRTAG YRLAYEVIDDEIWYVLAVG KRDKDAVYKKLASRFG KRDKDAVYKKLASRFG >gi|15601249|ref|NP_232880. 11 [Vibrio cholerae] MKVELVTSLKRQATKILADLHDTKEPVLITEHGKPSAYLIDVDDYEFMQNRLAILEGIAR GERALADGKWSHQDAKDRM SKWLK >gi|15601250|ref|NP 232881. 1| [Vibrio cholerae] MVEIIWTELALSDLNDIAEYIALENWAAKQLVQTVFTKVERLADFPESGRVPPELEHLNY REWWSPCRVFYKYDDAKV RILFVMRAERDLRRLMLTKQ >gi|15601264|ref|NP_232895. 11 relB protein [Vibrio cholerae] MTVPLEAFVSCPTPTPVLTFVHTTKELTMDTRIQFRVDEETKRLAQQMAESQGRTLSDAC RELTEQLAEQQRKALSHDAW LTEQVNQAFEKFDSGKAVFIEHDIAKARMAERKAKIRNRGHA >gi|15601263|ref|NP_232894. 1| [Vibrio cholerae] MIFWEEASLNDREKIFEFLYDFNPAAAKKTDELIEAKVENLLEQPLIGVQRDGIRGRLLI IPEISMIVSYWVDGSKIRIM RVLHQKQKFPND >gi|28898595|ref|NP_798200. 1| YefM protein [Vibrio parahaemolyticus RIMD 2210633] MKTILVPLNVHVEVLMRIVSFTEARNGLKAVLDGWNDADTTVITRRDSEDAWMSLDYYNS LMETVHLLRSPQNVEHLN RSIAQYRAGKTTARELIDE >gi|28898594|ref|NP_798199. 1| protein [Vibrio parahaemolyticus RIMD 2210633] MMSSSQRLLSWTDDAWDDYLYWQTQDKKTLKRINKLINDVKRSPFEGIGKPEPLKENLSG FWSRRIDDTNRLVYAVDDQA ITIISCRYHY ITIISCRYHY >gi|28898603|ref|NP_798208. 1| RelB protein/Vco27A protein [Vibrio parahaemolyticus RIMD 2210633] MDTRIQFRVDEETKRLAQQMAESQGRTLSDACRELTEQLAEQQRKSLSHDAWLTEQVNLA FEKFDSGKSVFVEHQTAKSQ MEERKARIRNRGKQ >gi|28898604|ref|NP_798209. 11 [Vibrio parahaemolyticus RIMD 2210633]

MILWEEESLNDREKIFEFLYDFNPDAAEKTDNLIEANVENLLEQLLMGVQRDGVRGRLLI IPEISMIVSYWIEGDIIRIM RVLHQKQKFPMD >gi|28898616|ref|NP_798221. 1| RelB protein [Vibrio parahaemolyticus RIMD 2210633] MFVSCPSQSLVLTFVHTPTKEYIMDTRIQFRVDEETKRLAQQMAESQGRTLSDACRELTE QLAEQQRKTLSHDAWLTEQV NLAFEKFDSGKSVFLEHQTAKSRMEERKARIRNRGKQ >gi|28898617|ref|NP_798222. 11 [Vibrio parahaemolyticus RIMD 2210633] MILWEEESLNDREEIFEFLYDFNPDAAEKTDNLIEAKVENLLKQPLMGVQRDGIRGRLLI IPEISMIVSYWVEGDIIRVM RVQHQKQKFPTD RVQHQKQKFPTD >gi|27365728|ref|NP_761256. 1| Antitoxin of toxin-antitoxin stability system [Vibrio vulnificus CMCP6] MKVELVTSLKRQATKILADLHDTKEPVLITEHGKPSAYLVDVDDYEFMQNRLAILEGIAR GERALADGKWSHDEAKDKM SKWLK >gi|27365729|ref|NP_761257. 1| Plasmid stabilization system protein [Vibrio vulnificus CMCP6] MAEIIWTEPALSDLNDIAEYIALENIVAAKQLVQAIFSKVERLEAFPESGRIPPELEHLS YREVWNPCRIFYKQDGDKV FILFVMRAERDLRKFLLSKQ FILFVMRAERDLRKFLLSKQ >gi|27365748|ref|NP_761276. 1| Antitoxin of toxin-antitoxin stability system [Vibrio vulnificus CMCP6] MKVELVTSLKRQATKILADLHDTKEPVLITEHGKPSAYLVDVDDYEFMQNRLAILEGIAR GERALADGKWSHDEAKDKM SKWLK >gi|27365749|ref|NP_761277. 11 Plasmid stabilization system protein [Vibrio vulnificus CMCP6] MAEIIWTEPALSDLNDIAEYIALENIVAAKQLVQAIFSKVERLEAFPESGRIPPELEHLS YREVVVNPCRIFYKQDGDKV FILFVMRAERDLRKFLLSKQ FILFVMRAERDLRKFLLSKQ >gi27365845IrefINP_761373. 11 Antitoxin of toxin-antitoxin stability system [Vibrio vulnificus CMCP6] MSRIHFDQDIQPLSEFRAGVTSFIKQINETRRPLVITQRGKGVAVVLDVAEYEAMQEKIE LLEEMRTAEAQLASGLGVSN EDARAQVLGRIKK >gi|27365846|ref|NP 761374. 1| Plasmid stabilization system protein [vibrio vulnificus CMCP6] MKVVWSPLALQKLGDAAEFISLDNPVAAESWVNEVFDKTELLSNMPEMGRMVPELPHTNY REILFGHYRIIYSLSHEIRV LTVRNCRQMLTESDV >giI27367843IrefINP_763370. 1I DNA-damage-inducible protein J [Vibrio vulnificus CMCP6] MDTRIQFRVDEETKRLAQQMAESQGRTLSDACRELTEQLAEQQRKTLSHDAWLTEQVNLA FEKFDSGKSVFIEHQTAKSR MEERKARIRNRGKQ >gi|27367844|ref|NP_763371. 1| Plasmid stabilization system protein [Vibrio vulnificus CMCP6] MILWEEESLNDREKIFEFLYDFNPDVPEKTDNLIEAKVENLLEQPLMGVQRDSILGRLLI IPEISMVISYWVEGDIIRVM RVLHQKQKFPTD RVLHQKQKFPTD >gi|21229536|ref|NP_635453. 11 [Xanthomonas campestris pv. campestris str. ATCC 33913] MQLQTHNQTRVLATKANAPRRFGSFESALKVLREMGMPLDVLHVDAARWDAEGGKTKRRP ERSEAMNVKELDARYAVSLR TQTEHALADPRPALSSAQAKQQMETLKTQQRAALEAALAAKGTRA >gi|21229535|ref|NP_635452. 1| protein [Xanthomonas campestris pv. campestris str. ATCC 33913] MSVAWKQSALDARTALLTSALARAIEIPDPQMYSAACEQDDRIETEGDALDGAAIYHSGP LPGTRLTTCQDGRYLLIYTR DGDDVLILVLVPARSDGKPTSSGDQ DGDDVLILVLVPARSDGKPTSSGDQ >gi|21230523|ref|NP_636440. 1| [Xanthomonas campestris pv. campestris str. ATCC 33913] MKSASLPSLRVDPALREAAEAVLQEGETLSSFVEHSVRAQVQQRQQQEAFIARGLASRDS AKASNRYIEAKDVLAGLQSQ LDKARKG

>gi|21230524|ref|NP_636441. 1| [Xanthomonas campestris pv. campestris str. ATCC 33913] MGYSVRFTQYARNDLARLYDWLLQRAESGFTWERALQAIRDGVTVLALAPLSCRKAVPAD PFLRELVIGFGASGYVLLF EVESNQWTVLAVRHQREDDYH EVESNQWTVLAVRHQREDDYH >gi|21230492|ref|NP_636409. 1| [Xanthomonas campestris pv. campestris str. ATCC 33913] MPLPGGTLWQSLPSGRCMATMNISLPDELKEFVDQQVLEHAYGSSSEYLRELIRMQRDAQ SLRALLLDGAESGPAVAMEA DFFDSMRARARQRAAGK >gi|21230493|ref|NP_636410. 1| [Xanthomonas campestris pv. campestris str. ATCC 33913] MKPARWRPLALRDVDEAAAWYGAEGGLALELAFTKALESAVTTLMRNPAAGSSRHAWLKL PQIRVWPLKRFPYLLFYNE RATDIVIWRVLHMQRDIPAWMSAHP RATDIVIMRVLHMQRDIPANMSAHP >gi|21241894|ref|NP_641476. 1| [xanthomonas axonopodis pv. citri str. 306] MPSGGGMATMNISLPDELKQFVDQQVAEHAYGSSSEYLRELIRKQRDIEQLRGVLLGGAN SGPAVAAEAGFFNAMQARAN ARAGEQ >gi|21241895|ref|NP_641477. 1| [Xanthomonas axonopodis pv. citri str. 306] MKPAHWRPLALRDVEAAAAWYGEQAGLEVELAFVDALVSAVDMLVQHPSAGASRYAVM ------------------------------------------------------------ ------------- >gi|15838658|ref|NP_299346. 1| protein [Xylella fastidiosa 9a5c] MKEQPHQSEGIPSAFTGESRRVADFLLAWWNVDSCGSFDLTALWGLGDAITVDMTTVFTC IARVSKYPDSLGYEADFKAI LRQWRPESAY >gi|15838657|ref|NP_299345. 11 conserved plasmid protein [Xylella fastidiosa 9a5c] MAKAKTPYRIKWRPKASEDLRDIVRYIGKNNPTRARSFGQELRDKTLPLAQHPEIGRTGR PGLPDYVRELVTHRNYIVFY RVLDETRTVEILRVKHVAQQMP >gi|15838666|ref|NP_299354. 1| protein [Xylella fastidiosa 9a5c] MGMATSIKLDDELKGRVQHLADVRRRTSHWIMREAIAQYVEREEKRETFRQDTLKAWEEF QATGLHVTTEEVEKWLSSWG TENELSAPVCHG >gi|15838665|ref|NP_299353. 11 protein [Xylella fastidiosa 9a5c] MPRVIFAPEAILNIQRLRNFLHPKNTDAARRAGEAIMRGARMLGAQPHIGRPVDDMPDEY REWLIDFGDSGYVARYHIDG DTVTILAVRHHKEVGYTS DTVTILAVRHHKEVGYTS >gi|15838672|ref|NP_299360. 1| DNA-damage-inducible protein [Xylella fastidiosa 9a5c] MAANQLVQARIDGAIKAEATWLAAMGLTISDAVRLLLTKVAQDKALPFEPLIPNATTIKA MREARAGKGETVTLGELRA TIRAGN >gi|15838671|ref|NP_299359. 1| [Xylella fastidiosa 9a5c] MREIKQLGQFKRDLKREAKGQHRATLEDDLLPVIDALAKDMPLEPRHRDHALLGNWKDLR DCHIKLDLVLIYTRVDSKTL TLVRLGSHAELGL TLVRLGSHAELGL >gi|28199073|ref|NP_779387. 1| anti-toxin protein [Xylella fastidiosa Temeculal] MEMPIGRSHLRYNEYMHLSGGFDMATSIRLSPEMEQRLNSLASHTGRTKAYYLREIIEHG IEEMEDYYLAADVLERVRHG QEQVHSAADVRKTLGLDD >gi|28199074|ref|NP_779388. 11 toxin-like protein [Xylella fastidiosa Temeculal] MAWTIDYTDTAKQQLRKLDKHMARRIVDFMDERIAGLENPRSSGKALTGPLGGFWRYRVG DFRWCAIQDSVLRVLWRV GHRGEIYR GHRGEIYR >gi|16272650|ref|NP_438868. 1| protein [Haemophilus influenzae Rd] MALTNSSISFRTVEKTKLEAYQVIEQYGLTPSQVFNMFLAQIAKTRSIPVDLNYLRPNKE TLAAIDELDSGNAESFFIEA SENYSAEEFTKRILNGGQ >gi|16272651|ref|NP_438869. 1| protein [Haemophilus influenzae Rd] MSEEKPLKVSYSKQFVRDLTDLAKRSPNVLIGSKYITAIHCLLNRLPLPENYQDHALVGE WKGYRDCHIQGDLVLIYQYV IQDEFDELKFSRLNIHSQTALK >gi|15595323|ref|NP_248815. 11 protein [Pseudomonas aeruginosa PA01] MSTWSFRADDALVAALDELARATHRDRPYHLRQALAQYLERQQWQVAAIDEGLADANAGR LLEHIEIEKRWGLQ >gi|15595322|ref|NP_248814. 11 protein [Pseudomonas aeruginosa PA01]

MSLKWTRKAAADLDAIYDHYWLIGPEKALKAVQDIVEQVKPLQQVANQGAGRPSEVPGVR TLTLERWPFSAPFRVKGKE IQILRIDRVEITP IQILRIDRVEITP >gi|26989222|ref|NP_744647. 1| [Pseudomonas putida KT2440] MATSIKIDDDLKGRIQHLACLRQRSSHWIMREAITQYVEREEARESFKQEALASWAAYQE TGQHLTGQEARTWLGSWGTD AEAELPKCHD >gi|26989223|ref|NP_744648. li [Pseudomonas putida KT2440] MPRLIVTEGAAKGLERCRRFLSDKDPQVARRAAQAIERQFARLEESPEVGRPFPDLPELR ELIIEFGDSGYVALYRYERA DDTAYVLAFRHQKEAGY >gi|26989659|ref|NP_745084. 11 [Pseudomonas putida KT2440] MHVLTFSQARAELKQTMDDVCRDHEPAVITRQRGEPWMMSLEDYNGMNETIHLLGSSKNA SRLRSSIAQLRDGQALTKE LDLNEQEPEAAEQE >gi|26989658|ref|NP_745083. 1| [Pseudomonas putida KT2440] MKFTKEGWEDYCHWQNADLTILGNINRLIDVCLRTPFTGIGKPEPLKGDLSGLWSRRITR EHRLVYFFEAGMLTVLQCRY HYDD HYDD >gi|28867568|ref|NP_790187. 1| prevent-host-death family protein [Pseudomonas syringae pv. tomato str. DC3000] MQVLSFSQARAGLKQAMDDVCRDHEPALITRLRGDHWMLSLDDYNSMSETMYLLGTEANA KHLRQSIAQHKAGKAFVKE ISLDVTGSETEE >gi28867567ref] NP790186. 1 [Pseudomonas syringae pv. tomato str. DC3000] MHFTLSGWDDYTHWKDADQAISLSIDSLISQCLRTPFKGTGKPRPLTGDLTGYWSRRITK EHRLVYFYEGGVLTVIACRH HY HY >gi|28870831|ref|NP_793450. i| [Pseudomonas syringae pv. tomato str. DC3000] MSVMSLRLPDEMADTLAHLAKATGRSKSFLALNALREYLTREAWQIAEIQRAIEEADAGE FASEEDVKAVMNKWANNAG >gi|28870832|ref|NP_793451. 1| [Pseudomonas syringae pv. tomato str. DC3000] MQVEWLKTALKNLDDEAAYISLENPAAAVAFVEALQISVKQLASFPALGREGRIAGTREW PLPDWPYLIPYRIRNGRLQV LRIFHTRRQPPLVW LRIFHTRRQPPLVW >gi|28872496|ref|NP_795115. 1| stability cassette protein, [Pseudomonas syringae pv. tomato str. DC3000] MASINVRIDDDLKARAYLELEKLGVTPSELLRQTLQYVAERGQLPFKTVLMTEEDEALLA TVRERLAAPQRVKVSLDDL >gi|28872495|ref|NP_795114. 1| stability cassette protein, [Pseudomonas syringae pv. tomato str. DC3000] MTYSLEFDARALKEWRKLGDTVRQQLKKKLATILVAPRVEANRLHALPDCYKIKLRSSGY RLVYQVIDQEVWFWAVDK RERDEVYRKAADRLSG RERDEVYRKAADRLSG >gi|16764896|ref|NP_460511. 11 cytoplasmic protein [Salmonella typhimurium LT2] MAFQILTTTAASITELKRDPMGTFNAGDGAPVAILNRNEPAFYCVPPALYAHLMDILEDE ELGRIIDERANERVIEVNID DL >gi|16764895|ref|NP_460510. 1| cytoplasmic protein [Salmonella typhimurium LT2] MTYKLAFNESALKEWKKLGHTIQEQFKKKLRERLENPRVPASQLHGRKDQYKIKLRGAGY RLVYSVEDEIITVTVIGVGK RENDAVYKMTRHRS RENDAVYKMTRHRS >gi|16766805|ref|NP_462420. 1| DNA-damage-inducibile protein, resembles dinJ [Salmo- nella typhimurium LT2] MAANALVRARIDETLKDQAADVLAEMGLTISDLIRITLTKVAREKALPFDLRIPNELTSR TIENSEAGVDIHKAKDADDL FDQLGI >gi|16766804|reflNP_462419. 11 cytoplasmic protein [Salmonella typhimurium LT2] MGQREIEYSGQFQKDVKRAQKRHKDVGKLKTLMTLLIHHPFPLPAIYKDHPLQGSYSGYR DAHIEPDWILIYKITDECLR FERTGTHADLF >gi) l6767695ref) NP463310. 1 helix-turn-helix protein, copG family [Salmonella ty- phimurium LT2] MATLNVRLDDKLKNEAYAVLEKLNITPTEAVRLLFQYVAETGRMPVKTVTLSDSEDALIQ TVRERLSSPQKGIKVSLDDL >gi|16767696|ref|NP_463311. 1| inner membrane protein [Salmonella typhimurium LT2]

MTYELEFDPRALKEWHKLGDTVKAQLKKKLADVLLNPRIDSARLNGLPDCYKIKLKSSGY RLVYQVRDDWIVFWAVGK REHSAVYHDANKRL REHSAVYHDANKRL >gi|16763249|ref|NP_458866. 1| RelB protein [Salmonella enterica subsp. enterica se- rovar Typhi] MATLNVRLDDKLKNEAYAVLEKLNITPTEAVRLLFQYVAETGRMPVKTVTLSDSEDALIQ TVRERLSSPQKGIKVSLDDL >gi|16763250|ref|NP_458867. 1| [Salmonella enterica subsp. enterica serovar Typhi] MTYELEFDPRALKEWHKLGDTVKAQLKKKLADVLLNPRIDSARLNGLPDCYKIKLKSSGY RLVYQVRDDWIVFWAVGK REHSAVYHDANKRL REHSAVYHDANKRL >gi|29144728|ref|NP_808070. 1| RelB protein [Salmonella enterica subsp. enterica se- rovar Typhi Ty2] MATLNVRLDDKLKNEAYAVLEKLNITPTEAVRLLFQYVAETGRMPVKTVTLSDSEDALIQ TVRERLSSPQKGIKVSLDDL >gi|29144729|ref|NP_808071. 11 [Salmonella enterica subsp. enterica serovar Typhi Ty2] MTYELEFDPRALKEWHKLGDTVKAQLKKKLADVLLNPRIDSARLNGLPDCYKIKLKSSGY RLVYQVRDDWIVFWAVGK REHSAVYHDANKRL The following sequences were found later in a supplementary search : >relB|23464628 : 1284380-1284766, length 129, Bifidobacteriumlongum, relB MRIRQAIWSLRERPALSLPPSSSPAMSIRPRSRAVASSSSSSMGAKEPSSTWRWSVSSAS SMRCSSSAVRSPARPRARAWAREPAMSSSAKRQSNCVDLDSRANSGDGPDVKRPPHRARC SLFSVMKAP >relE|23464628 : 1284736-1284981, length 82, Bifidobacterium_longum, relE MFWLSHEGSLKPWIANKSDCLSDYQRWATYRWIQWRIPWRQCQGYWSRRIDEKNRIVY RITGNDVQNLEIAVCRTHYGEH >gi|15645620|ref|NP_207796. 1| hypothetical protein HP1005 [Helicobacter pylori 26695] MSNIITDYSQYNEKQLHNFLNSIEKQLLKAERDKNKAIKKIQECELQERMIRQVLAQKHS QEKEPTPSLLNTIASKDDPE YDVSFGDFNDFLQIAKQERERHNA >relE|15644634 : 1067530-1067742, length 71, Helicobacterpylori26695, relE MTESDVTSIVDCLKKQKPLQQKYCDHALSGNLKGLRECHVKPNLLLIYEIKKQENELVLL RLDTHSELFKK RLDTHSELFKK >relB|13470324 : 250975-251220, length 81, Mesorhizobium loti, RelB MAMTAFTVRLSDDTTDRLDQLAEKLDRSRSYVAAQAIEDFVTRQEWQLAEIEAGLAEAER GEFANEQELAAVIAKYIKPAG >relE|13470324 : 251223-251513, length 97, Mesorhizobium loti, RelE MSHKTIRWTKRALRRLDEIGAHIEKDSPEAASRVIARILSAAELLTQQPAMGRVGRIKAT RELVLVDIPYIVPYRVSGNTVEILTVIHAAQQWPRTL RELVLVDIPYIVPYRVSGNTVEILTVIHAAQQWPRTL >relBJ20088899 : 3293160-3293339, lenth 60, Methanosarcina_acetivorans, relB MTETELLKKISDDLDFLKTKILEIEESLELIDSELHPIREEYKRLDEIKKQRGNYFRKRI >relE|20088899 : 3293349-3293555, length 69, Methanosarcina_acetivorans, relE MRGKALRYSYEISRHLERDLEKIQKKDRERFEILLDKMSEILDNPHRFKPLMHDMEGLMV NLYLIGIIY NLYLIGITY >relB|15839372 : cl388510-1388731, length 86, M. _tuberculosis_CDC1551, RelB MPTTWRSPRQRHATCNAYPKRSPPHVSSLFSDRCLTTRIGWASRCAMTLKASTQPAAVIT ASSTPSTTATTESRSSTSLVAVPATE >gi|15840691|ref|NP_335728. 1| hypothetical protein MT1284 [Mycobacterium tuberculosis CDC1551] MTWRPSRKRWRCYAPLAPARPFVKASPMLPQALREQRRDPQPLHRAVSDDHPYHVAITAT AARDLQRLPEKIAAACVEFV FGPLLNNPHRLGKPLRNDLEGLHSARRGDYRWYAIDDGHHRVEIIHIARRSASYRMNPCR PR >relB|15839372 : 3171692-3171970, length 93, M. _tuberculosis_CDC1551, RelB MRILPISTIKGKLNEFVDAVSSTQDQITITKNGAPAAVLVGADEWESLQETLYWLAQPGI RESIAEADADIASGRTYGEDEIRAEFGVPRRPH

>relE|15839372 : 3171947-3172237, length 87, M. tuberculosis-CDC1551, RelE MRRPATPPLSGALHRAVHHNRASRPPQAATANPRGSGRIRVRRSVARAPAGGQAPSARVG RHVQRASRNVPPAVPD RHVQRASRNVPPAVPD >gil15922557|ref|NP_378226. 1| 67aa long conserved hypothetical protein [Sulfolobus tokodaii str. 7] MLIMHWTLSDMFTEAGVYVKKNGKWRMFALAHYKYDNPCKWFSNLCWFHTPINCILYYSP ILFLMKY >gi|15922558|ref|NP_378227. 1| 105aa long hypothetical protein [Sulfolobus tokodaii str. 7] MVCEKWELKFMFRKRINDLEELSEFLASEFPHEEWMLIFDKLYLLREDPKKYAREKLKNQ TDKDGRPLFSIEVTGDIRI IYSFDSKGCTVFIWRIGKHKKAYRF IYSFDSKGCTVFIMRIGKHKKAYRF >gi|16330633|ref|NP_441361. 1| hypothetical protein [Synechocystis sp. PCC 6803] METINYQQFSEKLPTLVEKIGNEQEPLCLELPNYLRAVIISEQDYRSLMETVYLLSNPVN AEKLLTTASRSIDQATSWTK VKNDLGL >relEI16329170 : 1620536-1620793, length 86, Synechocystis_PCC6803, relE/yoeB MKEWLDSQAIEDIKWWIQQDKKLALKIMELIETLPKSPFAGKGKPEKLRFNLSGFWPRR ITQEHRLVYEVTDDFIRWSCRYHYR ITQEHRLVYEVTDDFIRWSCRYHYR >gi|16331058|ref|NP_441786. 1| hypothetical protein [Synechocystis sp. PCC 6803] MKAITTTQAKDHLDELINAVISDLEPTIVSNNQGQQAVLISLDEFNSWQETLYLLSNPTN AEHLMASIKQAETGQIIKQK LPDLLEL >relE|16329170 : 1620536-1620793, length 86, Synechocystis_PCC6803, relE/yoeB MKEWLDSQAIEDIKWWIQQDKKLALKIMELIETLPKSPFAGKGKPEKLRFNLSGFWPRR ITQEHRLVYEVTDDFIRWSCRYHYR ITQEHRLVYEVTDDFIRWSCRYHYR >gi|15838297|ref|NP_298985. 11 hypothetical protein XF1696 [Xylella fastidiosa 9a5c] MEMPIGRSHLRYYEYMHLSEGFDMATSIRLSPEMEQRLNYLASHTGRTKAYYLREIIEHG IEEMEDYYLAADVLERVRHG QEQVHSAADVRKTLGLDD >relE|15836605 : cl620819-1621091, length 91, Xylella_fastidiosa_chr, relE MAWTIDYTDTAKQQLRKLDKHMARRIVDFMDERIAGLENPRSSGKALTGPLGGFWRYRVG DFRWCAIQDSVLRVLWGVGHRGEMYRREC DFRWCAIQDSVLRVLWGVGHRGEMYRREC >relBJ28197945 : 1298015-1298314, length 100, XylellafastidiosaTemeculal, relB MYRLAQWDAIKRLSGVHVHSAHAQQLGGTHWAVSCGGFSEGSMHLAMTQSECLGIIELQ CSSFLTGYRRIALCLQTQLSVPALTRTSKKKHQPCWRRWA >relE|28197945 : 1298354-1298761, length 136, XylellafastidiosaTemeculal, relE MPARRRCRSSRWCRTKLPSQPCVKPVLVTSRALIVLRRSWRTCMRRISQTGQFKRDYKRE AKGQHRATLDEELIHVLEALTCDHPLEPRHHDHALTGDWKDHRDCHIKPDLVLIYRKPDN ETLQLVRIGSHSELGL ETLQLVRIGSHSELGL >gi|22126965|ref|NP_670388. 1| Hypothetical protein y3089 [Yersinia pestis KIM] MIMAKARLHDDAMVQLLMEDPEFAQVYLHQALLDIDEEGGQEAFLMALRHWEARGGMASV AKKAGVSRETLYRTLSPSG NPTLKTLLSWSATGFQFSHLASITA >relB|22123922 : c3399757-3400077, length 107, Yersinia_pestis_KIM_chr, RelB MLMKTIKHYLTPEGRDLYMEYLKSLRDSIAKAKISSRVNRIASGNFGDHKPCREGVWELR IDQGPGYRVYYSLVDGEWLLLLGGDKRSQNADIDQAIVCLKDYLTR Homoloques of phd/doc toxin-antitoxin system Polypeptides >gi|24473558 : 1143830-1143531, length 97, Phd MTDKKPFALSEVAQRVLIVLGRENRGLTVRELVEKTDTNSGSIKRALEELAKLNLIKEEK ENVFPYRRLISLTEVGREVAKRVIEIEELVKKVQSNG >gi|15921403|ref|NP_377072. 1| 152aa long [Sulfolobus tokodaii] MENKLMQILEGLLNEFEKWRSRESDRVPTIIQIHDSITRNDPNTERGIVNLDTIGITIYS AIENLSLYHDISRSLAVLTY RLITSHPFVDANKRTAFVLLLDILYELFDKEIPQDLEEELIKTLAEVADNPPEEDEYAIN KIRETIRQIIEG ------------------------------------------------------------ ------------- >gi|28209834 : 2057179-2057481, length 101, Phd

MILGLIYPKIVYNITIEEVLFMQVNINNLVSISEANQNFSRVARMVDENGAAIILKNNAP RYVLIDYSKFQQDTIADDATVEEAANNILNKHLKAFEELAK >gil28211562lreflNP_782506. 11 death on curing protein [Clostridium tetani E88] MKHLSKEQMMYLHSMAVKKTGGLDGIRDEGLLDSALNSPFQSFAGEELYPSIQAKAARLG FSIIKNHPFLDGNKRIGMLA MMVFLEINGIQLECSDEDIVDIGLGIASGKYEDDYIIDWIISCSNNS MMVFLEINGIQLECSDEDIVDIGLGIASGKYEDDYIIDNIISCSNNS >gil16124256 : 3613915-3613552, length 121, Phd MAFEEGFEFLVGDVGIDGHDAGMRERALAVKGAVRYNVCSNVWSAAMIALKLSQIGNSVG VVLPKEALVKLGVEKGDTLYLTDAPGGGMQIAPYDPDVARQIALGEEIMDEYRDTFRALA K >giil6127593irefiNP422157. 1t death on curing protein [Caulobacter crescentus CB15] MSGVGEPVWVRIEALKVLHERSLALHGGPSGVRDEGLLESALERPKNRFHYEGVDDVVEL AATYAVAVSSNHPFVDGNKR AAFHAMTLFLRLNGLRLVADQADAARTIFKLAAGELDIPALTDWLRTRVA >gi115675948 : 929630-929475, length 52, Phd MPANRQGAAMQNQNTRPVKIELKGEAGKRVLLAAARRIAKTHQKAVKALADK >gi|15676812|ref|NP_273957. 1| death-on-curing protein [Neisseria meningitidis MC58] MIDGELVALIHQTVLADEAGLKGRADMARLDGALSRIANWRQYENLEDIYEIAALYAQAI AKAHAFPDGNKRTALLTMLT YLDLQGISIAADQGLDDLIVSLAAGETDFKQLAETLRRLDKE YLDLQGISIAADQGLDDLIVSLAAGETDFKQLAETLRRLDKE >gil30248031 : 1386749-1386501, length 83, Phd MVITLGYEMIELKVRKFGNSLGIVLPKEVVNHLRTGDGQRLFLTEASDGRYLITPYDPSF GEKMAKVEDICNRYRNTLHVLTK >gil30249247lreflNP_841317. 1| putative death on curing protein [Nitrosomonas europaea ATCC 19718] MTTPVWINEQDVLAIHERLIFLHGGASGIRDRNLLKSALARPLNFSVYDQQSDIFLLAAT YTSGILQNHPFVDGNKRTGF VIGVLFLELNGYKFIANEEDSAQAIISLAEGSLDELGFRLFIEHNSIAT >gil30248031 : 2674530-2674754, length 75, Phd MVELKVRKLGNSLGVVLPKEVINHLRTGDGQRLFLTEASDGGYLITPYDPAFEEKMVKVE NICDRYRNTLRILAK >gil30250372lreflNP_842442. 1l putative death on curing protein [Nitrosomonas europaea ATCC 19718] MIEPIWIDEQVALAIHERLISLHSGASGVRDKELLKSALARPLNLLAYDQQADVIHLAAA YTAGILQNHPFVDRNKRTGF VVGVLFLELNGYRFTAAEEDSAQAVIALAAGSLDEARFKLFLADNSIPV VVGVLFLELNGYRFTAAEEDSAQAVIALAAGSLDEARFKLFLADNSIPV >gil22123922 : 2738880-2738578, length 101, Phd MQLIRYSLSYTLCINKNGYNPFTTAENSMCQRFSIYNSEDNVMSHALKNADRLYIPPRDK GTKAYPRASMDTSSTHADQVKNAFAFGFSRYEKAMEELSKV >gil22126357lreflNP_669780. 1l [Yersinia pestis RIM] MADIVEGIHYLSVEDFIYINRTLIEAQTPSEPIDVINHNNLCSSQARPSVVKYYQQTDDM FELSAALIESLIQNHAFANA NKRTAMMAGYMFLLLNGYELTAPGDEIVVMAEGMARKVYNCEDLENWLCYWSRPYDSRNL CDCEISSLVVTATQVKIE gill5595198 : 69056-69187, length 44, Phd MSQDQQGIRYLSVADLVRLNELLILAQTPDEPIGVLKPNELESA >giU5595251ireftNP248743. 1) [Pseudomonas aeruginosa PA01] MNHCFANGNKRTAAAAATVFLLLNGIELTGPAQDFVDIMVALVTREASVQDLEDWMFYWH RPFDAYNLPDSDAFERMVAR LGIG LGIG >gi|21226652|ref|NP_632574. 1| protein [Methanosarcina mazei Goel] MSTIAIDPDVKESLKELKLAPEESYNSVVKRLIGEVKKKEDYSPMFPKEEKQGHKESHIN DFDAWLEKKLVEDKNILDAL GRK >gil21226651lreflNP_632573. 11 conserved protein [Methanosarcina mazei Goel] MEESDVLISLIEILKIHQKVIDYDKFKDPEDYTPAIRSLATLELMFEYLIKESNTIFENA AVIVYTIVAKHPFFNGNKRT GYEAMNFIIEDGGYGFTSTDEEMIEFIIRVATTENEMSIEEIKEWIIRHTEKIL ------------------------------------------------------------ ------------- >gi|21224247|ref|NP_630026. 1| protein [Streptomyces coelicolor A3 (2)] MAMTLRLPDDLDTKLTERARGEGCSKQELAIGAIRDARDRAELKVDDVLAGLMDSDAEIL DYLK

>gi|21224248|ref|NP_630027. 11 protein [Streptomyces coelicolor A3 (2)] MSGVRYLQIDEILAIVRTVNGAEHSVRDMGLLVSAIERPRTNVFGAELYPTLHEKPRHYC TPSPAITR ------------------------------------------------------------ ------------- >gi|21218953|ref|NP_624732. 1| protein SCF51. 10 [Streptomyces coelicolor A3 (2)] MTFTEEEMEGVRAAAAAEGKSLKQYMHDLGVREMQRKRFVAGAVSWADRLRAEFDEAFPD EIPPSQRGEGVTAA >gi|21218954|ref|NP_624733. 1| protein SCF51. 11 [Streptomyces coelicolor A3 (2)] MSEPLYIDVPWLLDVQDAALDNEDVSVTDYSALVAAVARHKTRMPTLAASNPDSAWRAAA LLHTVVRLEPLPHRNSLFAA FVTGQYMDQSGEGIDPPYGALSDLIRKVRETRLSIYDIADVLRSWRI >gi|21673171|ref|NP_661236. 1| protein [Chlorobium tepidum TLS] MVKQLTKHGNSMAMVIDKPILELIGADADTPFEITTDGQALILTPLKNPKGGEAFGVALE KVNTRYARALKKLAE >gi|21673172|ref|NP_661237. 1| Doc protein [Chlorobium tepidum TLS] MRFLDLHEVLHIHRDQITRYGGTLGVRDMGLLTSAIAMPTAMFKGDFLHTDIYEMAAAYL FHLVRNHPFLDGNKRVGAVS AIVFLALNGYDFEAPENDLVEMVYGVARSEFEKSDVALFMRRWSVKW >gi|17227997|ref|NP_484545. 1| protein [Nostoc sp. PCC 7120] MIVSSSQLYERFIEQVIGLSQKKDFSLTALISNYVRMNYQLKLEQIDKLKAWLDGFRPFD QTMLAELKKLYDVRFTYNSN AIEGNTLTQSETELVLTKGITIGGKTLNEHLEVIGHKEAIDYIESLSQKDTEINEW >gi|17227998|ref|NP_484546. 11 protein [Nostoc sp. PCC 7120] MMAAGTNYIYPPHYLLSQLMADFVIWLNSNAALTLHPVEYATMAHYRFVSIHPFRDGNGR TARLIMNLLLIRAGYPIWVI NNQVRNDYINALAYGQQNQDDLSGLFDLVCDAVISSLVETLRLLVTASSSREKGQVFYQE IIDFIDKNVGK >gi|29375017|ref|NP 814170. 1| [Enterococcus faecalis V583] MEIKERKLRKVGNSVVMTLSKEFLESIGATATDTVYVDEEKLKDIIVKKNMSEHQKKLQQ MMENSKQKHNELYKELVTK >gi|29375016|ref|NP_814169. 1| death-on-curing family protein [Enterococcus faecalis V583] V583] TAVMATDLFLQLNGYDFQLDTQEGVDLLVFIATYRSDFDQLKNDVSKVIRAKLNHTSSH TAVMATDLFLQLNGYDFQLDTQEGVDLLVFIATYRSDFDQLKNDVSKVTRAKLNHTSSH >gi|15900771|ref|NP_345375. 1| protein [Streptococcus pneumoniae TIGR4] MVVKTRKQGNSITITIPSEFNIPSGVKYEAKLLPSGEIIFTPEELGQQVSYVSDDAFDLN LDKIFDEYDDVFKALVEK >gi|15900772|ref|NP_345376. 1| protein [Streptococcus pneumoniae TIGR4] MTIYLTEKQIEKINALAIQRYSPNEKIQTVSPSALNMIVNLPEQFVFGKPLYPTIFDKAT ILFVQLIKKHVFANANKRTA FFVLVKFLQLNGYRFSVTVEEAVKMCVTIAVEALTDEKMTSYSKWISEHSVREKVKK ------------------------------------------------------------ ------------- >gi|17987658|ref|NP_540292. 11 Protein [Brucella melitensis] MNITLRKIGDSYGVIIPKEVLERLNLQTGDTLTLTTDENGLRLARSTEDAEVLEKKMQIA RERMKKYETAYRVLAQ >gi|17987659|ref|NP_540293. 1| DEATH ON CURING PROTEIN [Brucella melitensis] MIDFHSRVFIEALHQEQLRLHGGATGIRDSSLLDSALARAQHKEAYGNPDIFDLAAAYLF GILKNHPFIDGNKRTGLAAA DLFLYFNGYSLEAEQEDVIQLVLMVTTSEIDETGARAFFRDHAWINED DLFLYFNGYSLEAEQEDVIQLVLMVTTSEIDETGAAAFFRDHAWINED >gi|23501447|ref|NP_697574. 11 transcriptional regulator, AbrB family [Brucella suis 1330] MNITLRKIGNSYGVIIPKEVLERLNLQTGDTLTLTTDENGLRLARSTEDAEVLEKKMQIA RERMKKYETAYRVLAQ >gi|23501446|ref|NP_697573. 1| death-on-curing family protein [Brucella suis 1330] MIDFHSRVFIEALHQEQLRLHGGATGIRDSSLLDSALARAQHKEAYGNPDIFDLAAAYLF GILKNHPFIDGNKRTGLAAA DLFLYFNGYSLEAEQEDVIQLVLMVTTSEIDETGAAAFFRDHAWINDD >gi|16122085|ref|NP_405398. 1| protein [Yersinia pestis] MQLIRYSLSYTLCINKNGYNPFTTAENSMCQRFSIYNSEDNVMSHALKNADRLYIPPRDK GTKAYPRASMDTSSTHADQV KNAFAFGFSRYEKAMEELSKV >gi|16122086|ref|NP_405399. 1| [Yersinia pestis] MADIVEGIHYLSVEDFIYINRTLIEAQTPSEPIDVINHNNLCSSQARPSWKYYQQTDDMF ELSAALIESLIQNHAFANA NKRTAMMAGYMFLLLNGYELTAPGDEIWMAEGMARKVYNCEDLENWLCYWSRPYDSRNLC DCEISSLWTATQVKIE >gi|15601235|ref|NP_232866. 11 acetyltransferase, [Vibrio cholerae]

MNLEEFQESDFDLLIKWIDSDELNYLWGCPAYVFPLTYEQIHSHCSKAEVFPYLLKVKGR HAGFVELYKVTDEQYRICRV FISNAYRGQGLSKSMLMLLIDKARLDFSATKLSLGVFEQNTVARKCYESLGFEVVMVVVI EFGGMRCQPLRRALCFLSRF GAIIGLTFIDSRCDMNRKVEAYGVDAVERPKIKAsKKLDLTGDAGRQIVKSETKLALRTH QKTFTKLADM >gi|15601236|ref|NP_232867. 11 doc protein [Vibrio cholerae] MDIICFPFERVIEINAFILKTEPGMKGAVDIPKLQGALGRIDNAIVYEGLDDVFEIAAKY TACIAVSHALPDANKRTGLA VALEYLSLNDFELTQENDLLADAVRDLVIGIINETDFADILYAQYAKEQNSAL ------------------------------------------------------------ ------------- >gi|21241949|ref|NP_641531. 1| protein [Xanthomonas axonopodis pv. citri str. 306] MKLKITAIGNSAGVILPKELLARLRLGKGDELYALETPDGIKLTAFDPTLAAQMDVAEQV MREDRQVLNKLAK >gi|21241948|ref|NP_641530. 1| death-on-curing protein [Xanthomonas axonopodis pv. citri str. 306] MNTRMLVWVTHALALAIHERQLSEHGGASGVRDEALLDSALARPQQLFSYGDPPPDLVGL TASLAYGLARNHPFVDGNKR TAHVCYRVFLLLNGAELIASQEEKYVAMMRLADGAWSEATFAQWLRPRVRLRADTHVHEP QGHYG ------------------------------------------------------------ ------------- >gi|16766845|ref|NP_462460. 1| cytoplasmic protein [Salmonella typhimurium LT2] MFMRTVNYSEARQNLAEVLESAVTGGPVTITRRGHKSAVIISAEEFERYQTARMDDEFAA IMAVHGNELRELADK >gi|16766844|ref|NP_462459. 1| homology to death-on-curing protein of phage P1 [Sal- monella typhimurium LT2] MTLQLISAEEIIQFHDRLLRVTPGVTGMPDPGRAEALMYRVLKQIEYEGVTDVWLLAAMH LLAISRGHIFNDGNKRTALF ITLLFLKRNGISLARNPDFVDMTVDAAAGRLTLEQIAVRLRA ITLLFLKRNGISLAANPDFVDMTVDAAAGRLTLEQIAVRLRA >gi|16759892|ref|NP_455509. 1| bacteriophage protein [Salmonella enterica subsp. en- terica serovar Typhi] MVLNCPQPLKVIINSLDVFTSYNLRKHCQTCMRVIIMGHALKKADRLYIPPRDKSMVAKP RAAISKACSHTGQVKNAFEF GFARYEKAMEELSKV >gi|16759893|ref|NP_455510. 1| bacteriophage protein [Salmonella enterica subsp. en- terica serovar Typhi] MAIEYVEGVNYLSIEDIVYINRSLIEIQTPNEPIGVLNPNNLSSSQSRPSTIRYYEQTDD MFRLSAVLIESLIQNHPFAN ANKRTAMMAGYVFLLLNGYELTAPSDEWTIAEGLARKDYAVDDLENWLCHWSREYDSRTL CETGGNMIQALVATSRYIR IKSNE The following sequences were found later, in a supplementary search : >gi|29142336|ref|NP_805678. 1| putative bacteriophage protein [Salmonella enterica subsp. enterica serovar Typhi Ty2] MVLNCPQPLKVIINSLDVFTSYNLRKHCQTCMRVIIMGHALKKADRLYIPPRDKSMVAKP RAAISKACSHTGQVKNAFEF GFARYEKAMEELSKV >gi|29142335|ref|NP_805677. 1| putative bacteriophage protein [Salmonella enterica subsp. enterica serovar Typhi Ty2] MAIEYVEGVNYLSIEDIVYINRSLIEIQTPNEPIGVLNPNNLSSSQSRPSTIRYYEQTDD MFRLSAVLIESLIQNHPFAN ANKRTAMMAGYVFLLLNGYELTAPSDEWTIAEGLARKDYAVDDLENWLCHWSREYDSRTL CETGGNMIQALVATSRYIR IKSNE IKSNE >gi|29833628|ref|NP_828262. 11 hypothetical protein SAV7086 [Streptomyces avermitilis MA-4680] MAKTQLNVRVDEGTARAARERALERGMSVNRYIEELVRQDTGEAGHTFVEAAADFMKQYE TVFAEEFGADREGTRESRR >gi|29833629|ref|NP_828263. 11 hypothetical protein SAV7087 [Streptomyces avermitilis MA-4680] MA-4680] MENLRIDLAGIAEQKTPGDPQVTDLGALVAAVSRHEAEIFGIPVYDTPHARAAALLQWSA VA YAYLVAGGAKWTSPEQVRELARLVKSGEAGVDDIARELRQWSL >gi|29827371|ref|NP_822005. 11 hypothetical protein SAV829 [Streptomyces avermitilis MA-4680] MSFTDEELEGVRAAAAAEGKSLKQYLHDLGVREMQRKQFVAGATAWADRLRREFDDAFAD EVPPSERRDGAAAA >gi|29827370|ref|NP_822004. 1| hypothetical protein SAV829 [Streptomyces avermitilis MA-4680] MHFYVDVSWLLDVQEAALGREDMSVSDYSALVAAIARHKTKLPTLAAADPDAAWFtAAAL MHTIVRLEPLPHRNSLFAAFI AAQYMDQSGEGIDPPYGALSDLVSKIRDTRLGILAVADQLRTWKV >gi|15921597|ref|NP_377266. 1| 91aa long conserved hypothetical protein [Sulfolobus tokodaii str. 7] MEYLTEMQQRVILALYYSGNEKVTFRKLIELTKSSTSPVKNAIDSLEEKGLVEEIEETES FPKRRYIKLTEKGKKVAEKL KELYTLIESTS

>doc|24473558 : cl328737-1329249, length 171, Sulfolobus_tokodaii, doc MYVDRVYFIRLNILLEEKLLKILNALLKEFEAWIRGESEEKPLIIEIHDKLIANDTYSEG GVINLDDIGIAIYSSIEDLMRNHDVSRSLAVLTYHLWSHPFVDGNKRTTLGFLLNILHT LFEDEIEIPQDWDTLMQTLVEIADNPPEEDEMAINRVRSIIRGLIPVNQD Homoloques of higBA toxin-antitoxin system polypeptides >gi|23308765 : 1085714-1086001, length 96, downstream antitoxin HigA MADLLPLERLGPRKRRDRGLSLRRRRWLRSSTRRFTLVRFSWRTSSRASASHRTRSPYRS GCLRDASTRSCTASDPSRPIRLCVSGGTSVSTRSSG >gi|23308765 : 1085499-1085777, length 93, upstream HigB toxin MIRSFADRDTELVWLREGAKRVDPRIHKVANRKLHLLDAATTLDALRVTPGNRLETLEGD RVGQYSIRVNDQWRICFRWNDSGPENVEIVDYH RVGQYSIRVNDQNRICFRWNDSGPENVEIVDYH >gi|15836605 : 1630197-1629883, length 105, HigA antitoxin MIRCSGTCSVRKTFFSGQIKVPVEALLQRLAGGAASMAPRPARIKMPHEAERWYQKMPQR DVRVLVGTDTRTTSYFDHQSLNLGRDRCRLKSNIITITLSVIWY >gi|15838310|ref|NP_298998. 1| [Xylella fastidiosa 9a5c] MEVKFEDPSLERLEANQKYTAGLVKVFHRRIQFIRASPDERAFYAMKSLHYEKLKDDPDN LYSMHLNDQWHLIMYLKAKE DDTRNLWIVSIVDYH DDTRNLWIVSIVDYH >gi|15599869|ref|NP_253363. 1| conserved [Pseudomonas aeruginosa PA01] MATNGMRPIHPGEILRDEFLMEFDISPAALARALKVSAPTVNDIVREQRGISADMAIRLG RYFDTSAQFWMNLQSEYSLA TAYAANGKQIEHEIEPLLAHG >gil15595198 : c5242573-5242848 MILTFRCDETRQLFETGLSRRWGAILTVATRKLAMLHAATELRDLRSPPGNRLEPLQGKR AGQHSIRINDQWRVCFVWTDAGPEEVEIVDYH AGQHSIRINDQNRVCFWTDAGPEEVEIVDYH >gi|21226647|ref|NP_632569. 11 protein [Methanosarcina mazei Goel] MAEALNSDKIKRSPTLNTIIMVEDAIQNSPNSVITIPELKKALPRQVNHNTLMTILEYLE KSNKIAVGLRGITWIHNTNH NLRNVAIYGREL >gi|21226648|ref|NP_632570. 11 conserved protein [Methanosarcina mazei Goel] MKRVSVRLTPEADEAYEYLISKASDSKQEETILNAFHQKIELIKNDVHYGNPVAKRLIPS EYKTKYGVNNLFRVELPGFW RMLYTLTAGNSGVETLVIVIDIIDHKKYDKAFGYKK KNLYTLTAGNSGVETLVIVIDIIDHKKYDKAFGYKK >gi|17230415|ref|NP_486963. 11 virulence-associated protein [Nostoc sp. PCC 7120] MARPPIHPGEILADEITELAMTASDLARVLHVPKNRITEIINGRRGITADTALRLGQYFG TGGEFWLNLQKNYELRLAEQ TSGKEIQETICPRILVS >gi|17230416|ref|NP_486964. 1| protein [Nostoc sp. PCC 7120] MSPSDEYPKYKDKRTEKFALGERVKEFQSFERQAQKRLDIIDAAPNKEVLMQLPSNRFES LGGDRKGQYSIRINEQWRIC FNWPDDFLKPFNIEITDYH >gi|28377334|ref|NP_784226. 1| plantaricin biosynthesis protein PlnY () [Lactobacillus plantarum WCFS1] MNEIPTPKISEILEEEFMAPLHISAYFLAQQIGVPTSRIQDLLHDRRQVTVDTSLRLGRF FGVSDRYFLELQNDIEIRNL KQIHGAEYAQIKKYQVS >gi|28377333|ref|NP_784225. 1| plantaricin biosynthesis protein PlnX () [Lactobacillus plantarum WCFS1] MPPTIQQLALRKLLMIDHAETINDLSLPPANHLEKLSHDRQGQYSIRINNQYRICFAIRN GNEFYDVEIVDYHHG ------------------------------------------------------------ ------------- >gi|27378122|ref|NP_769651. 11 virulence-associated protein I [Bradyrhizobium japoni- cum] MAKKLKPMHPGEVLREEFLVPLNMSAGALAKTCGLPRTRIERIANEQTGITADTALRLAK ALGTTAELWLNLQNDYDIQI AKRDLGKALDRIETVNRPQAAE >gi|27378123|ref|NP_769652. 1| bsl3012 [Bradyrhizobium japonicum] MIRTFRDKTTEAVFDGESPKGFPADLVKVARRKLRYLHAAGELGDLRAPPGNRLEALSGN RKGQHSIRINDQFRVCFIWT PQGPVEVEIVDYH >gi|13471567lref|NP_103133. 11 protein [Mesorhizobium loti]

MLMTARKPTTVGEILTEEFMQPLGLTQAALAEAMGVQRKHVNELCNDRRNVTAATALILA RVFGNSPDFWLNVQRRSDLW AVMNSPDERARVDRAKPLATAA >gi|13471566|ref|NP_103132. 1| protein [Mesorhizobium loti] MIVGFRDGWLRAFFVDDTRSRNIPSDLESRLFRKLQMIDDATVDQDLRVPPSNHFEKLRG NLEGFHSIRVNQQWRLIFRW DGGRGEASDIYLDDHSYK DGGRGEASDIYLDDHSYK >gi|15964803|ref|NP_385156. 1| [Sinorhizobium meliloti] MLTTKRKPATVGEILTEEFMRPMGLTQGALAEAMGVQRKHVNELCGNRRNVTAATALILA RVFGNSPDFWLNVQRRNDLW LVMNTPKERERIERARPLENAA >gi|15964804|ref|NP_385157. 1| [Sinorhizobium meliloti] MIVGFRDDWLRTFFVDDVRSRNIPYDLEARLFRKLQMIDDAATDQDLRVPPSNHFEKLRG NLAGLHSIRVNQQWRLIFRW DGTRGEADGIYLDDHSYR DGTRGEADGIYLDDHSYR >gi|15966811|ref|NP_387164. 1| [Sinorhizobium meliloti] MPGEILASEFLEPMNISARKLAGHIGVPANRITEIIKGRRSITGDTALRLSKAFGTTPEF WINLQSHYELERARDAAGDL SISPLHAA >gi|15966812|ref|NP_387165. 1| [Sinorhizobium meliloti] MIQSFGNKETEAVFKRQRTRRFGAFQKPALVKLLMLHAATRIEDLRVPPGNRLEALKGDR AGQYSIRINQQWRICFRFEN GDAYDVEISDYH >gi|30248496|ref|NP_840566. 11 Helix-turn-helix motif [Nitrosomonas europaea ATCC 19718] MTRPVNRMRAVHPGEVLREDFLIPAGISVNALAIALSVPATRIHEIVKERRAVTADTAER LAHYFGGDAASWLALQASYD LKTLPTRDEIERRVQRREEHV >gi|30248497|ref|NP_840567. 1| [Nitrosomonas europaea ATCC 19718] MGCMIQSFRCKSTQAMFEGECPQRFSAIQAVAERKLAQLEAAQTLDFLRSPPGNRLEKLA GDREGQWSIRINAQWRICFT WSDLDPADVEIVDYH WSDLDPADVEIVDYH >gi|30248505|ref|NP_840575. 1| Helix-turn-helix motif [Nitrosomonas europaea ATCC 19718] MNNKLTPVSPGEMLAEEFLIPLGMSNYRLAKEIGVSAQRIGEIVTGKRAITVDTDLRLCR FFGLSDGWWLRLQVDYDIEM ARGALEETLAKIRPWANTQEHGTPA >gi|30248506|ref|NP_840576. 1| [Nitrosomonas europaea ATCC 19718] MSFDANIATQYYILMTIKTFRCADPETLFKLGRVARFVNIERPALRKLKQLDLARCIEDI RVPPANRPEILKGDRAGQHS IRINDQWRVCFRWTGTDAEDVEIVDYH >gij30249099ref NP841169. 1j Helix-turn-helix motif [Nitrosomonas europaea ATCC 19718] MTIHIEELENMDFSDVAEGGKLHPIHPGEILREEFLMPLKITPHALSLALQIPATRINDI VRERRAITTDTALRLARYFG NTAEFWMGLQIDYDMTITRDSLRGALNRIQRFEPTHIS >gi|30249098|ref|NP_841168. 1| [Nitrosomonas europaea ATCC 19718] MIKTFATKETAALFANEKIRRLPPEILRVARRKMAQLHRVSSIEELRIPPGNRLEKLSGN RNEQWSIRINDQWRICFRFE AGDVFDVEITDYH AGDVFDVEITDYH >gi30249283) refNP841353. 1 Bacterial regulatory protein, LacI family : Helix-turn- helix motif [Nitrosomonas europaea ATCC 19718] MARMHNPPYPGETLREDVLPALGLTVTQAAKELGINRVTLSRVLNGKAGISVDLALRLEA WLDGPSAESWLKGQLAYDLW QAEQRGCAKVVVRHINREQI >gi|30249284|ref|NP_841354. 1| proteic killer suppression protein [Nitrosomonas eu- ropaea ATCC 19718] MIRHFKHKGLQLFFETGDKSGIRPDHASRLARQLRQLNDAVNPREMNIPGWKLHPLSGDL SGYWSVMVNGNWRMIFVFDG EDVILVDYRDDH >gi|26247766|ref|NP_753806. 11 protein yddM [Escherichia coli CFT073] MKMANHPRPGDIIQESLDELNVSLREFARAMEIAPSTASRLLTGKAALTPEMAIKLSWIG SSPQMWLNLQNAWSLAEAE KTVDVSRLRRLVTQ >gi26247767refNP753807. 1 protein [Escherichia coli CFT073] MNFRHKGLRDLFLLGKTSGVIPTQVKRLRHRLAVIDAACCLADIDMPGYRLHPLSGDRDG IWAISVSGNWRITFEFVNGD AYILDYEDYH

------------------------------------------------------------ ---------- >gi|29654781|ref|NP_820473. 1| proteic killer antidote protein, [Coxiella burnetii RSA 493] MAANRMRPIHPGEILAEELGFLDKMSANQLAKHLAIPTNRVTAILNGARSITADTALRLA KFFGTTPEFWLNLQDAYDIK MALKKSGKKIEKEVTPYDQAA >gi|29654782|ref|NP_820474. 1| proteic killer protein, [Coxiella burnetii RSA 493] MLDVTRKTVILEVIIKSFKDKYTKYLYKGVSVSKWQAIRKQAERRLQILDSVTSLDDLRS LPSNRFESLRGNRKGQFSIR INKQWRICFKWINNEPTEVEIVDYH >gi|15601230|ref|NP_232861. 1| [Vibrio cholerae] MSNRDLFAELSSALVEAKQHSEGKLTLKTHHVNDVGELNISPDEIVSIREQFNMSRGVFA RLLHTSSRTLENWEQGRSVP NGQAVTLLKLVQRHPETLSHIAEL >gi|15601229|ref|NP_232860. 1| protein [Vibrio cholerae] MKSVFVESTIFEKYRDEYLSDEEYRLFQAELMLNPKLGDVIQGTGGLRKIRVASKGKGKR GGSRIIYYFLDEKRRFYLLT IYGKNEMSDLNANQRKQLMAFMEAWRNEQS >gi|15601155|ref|NP_232786. 1| antidote protein, [Vibrio cholerae] MRKTKRRPVSVGEMLKVEFLEPMGITSKALAEAMGVHRNTVSNLINGGVLTAPVAIKLAA ALGNTPEFWLNIQHAVDLWD TRNRYQEEAKFVKPLFVSLEQSART >gi|15601154|ref|NP_232785. 11 killer protein, [Vibrio cholerae] MCTVSLCVSLCLWMHNETVQVAMALEFKDKWLEQFYEDDKRHRLIPSSIENALFRKLEIL DAAQAESDLRIPPGNRFEHL EGNLKGWCSIRVNKQYRLIFQWVDGVALNTYLDPHKY EGNLKGNCSIRVNKQYRLIFQWVDGVALNTYLDPHKY >gi|15837322|ref|NP_298010. 11 proteic killer active protein [Xylella fastidiosa 9a5c] MKRMHNPAHPGEVLREYLGDLTVTNAAAKLGVSRVALSRILNGANGISADMALRLEDALG TSAEMWVAMQFKYDLWVASQ QPRPKITRLHV >gi) l5837323refNP298011. 1 proteic killer suppression protein [Xylella fastidiosa 9a5c] MYTDHLRYTIGFVIKSFRHKGIQQFFLEGSTAGIQTKHAAKLRIQLTALESAKHPKDMNA PGWKLHSLKGADLKGHWSIW VNGNYRLTFAFEGEDAILVDYQDYH VNGNYRLTFAFEGEDAILVDYQDYH >gi|28198286|ref|NP 778600. 1| proteic killer active protein [Xylella fastidiosa Te- meculal] MKRMHNPAHPGEVLREYLGELTVTNAAAKLGVSRVALSRILNGTNGISADMALRLEDALG TSAEMWAAMQFKYDLWVASQ QPRPKITRLHV >giI28198285refNP_778599. 1 proteic killer suppression protein [Xylella fastidiosa Temeculal] MIKSFRHKGIQQFFLKGSTAGIQTKHAAKLRIQLTALESAKRPEDMNAPGWKLHPLKGAD LKGHWSIWVNGNYRLTFAFE GEDAILVDYQDYH >gi|28199225|ref|NP_779539. 1| virulence-associated protein [Xylella fastidiosa Temec- ulal] MRTVPYPTPGDILLHEFLEPMGITQYRLAKSIGVPQRRIGQIVSGDRAVTADTALRLSKF LGTSDGFWLGLQMDYDAAAT KDKLAETLSKITPWHTQAA >gi|28199224|ref|NP_779538. 1| proteic killer suppression protein [Xylella fastidiosa Temeculal] MAIQSLACQHTESLFNGKRIPRFVNIETVAMRKLAMLHRAAHVDDLRIPPANRLEMLKGH RKGQYSIRINDQFRICFTWT VAGPKNVEIVDYH VAGPKNVEIVDYH >gi|16273170|ref|NP_439407. 1| virulence-associated protein A [Haemophilus influenzae Rd] MMTRKPTSVGEILQEEFLEPLSLKISDLAQILDVHRNTASNIVNNSSRITLEMAVKLAKV FDTTPEFWLNLQTRIDLWDL EHNKRFQQSLANVKPALHRHDTSTFAM >gi|16273169|ref|NP_439406. 1| protein [Haemophilus influenzae Rd] MFNLKREHFRDDYLYRFYQYGDTHSKIPSNLYKVLARKLDMISASENINDLRSPPANHLE LLEPKENKIYSIRVNKQYCL IFKYENNEVNNLYLDPHSYNL >gi|26988317|ref|NP_743742. 1| antidote protein, [Pseudomonas putida KT2440] MLKNGMRPIHPGEILREEFQKEMGFSAAALARALGVATPTVNNILRERGGVSADMALRLS ICLDTTPEFWLNLQTAFDLR

TAEQQHGDEIIGSVQRLVA >gi|26988318|ref|NP_743743. 1| killer protein, [Pseudomonas putida KT2440] MIRSFSCADTEALFTTGKTRRGSDIKSVAERKLAMLDAATELRDLRSPPGNRLESLSGNR ADQHSIRVNDQWRLCFTWTE HGPVNVEIVDYH >gi|26987933|ref|NP_743358. 1| transcriptional regulator, Cro/CI family [Pseudomonas putida KT2440] MEIMEKHLFDRLVESMTQMDEIDRGERQPSREFHVDALQVKKIRQATGLSQAAFAKRIDV AVGTLRNWEQGRREPEGPAR ALLRAIHNDPEHVLAALS >gi|26987934|ref|NP_743359. 1} [Pseudomonas putida KT2440] MTHSRDCMIFIETPVFTSDLKEHLDDEEYRALQAYLAEHPEAGSLLEETGGLRKIRWAAK GKGKSGGVRVIYYHVTAAHQ IRMILIYRKGIVDTLTSSQKAQLRALNKGWK TRMILIYRKGIVDTLTSSQKAQLRAI, NKGWK >gi|28867446iref|NP_790065. 11 virulence-associated protein, [Pseudomonas syringae pv. tomato str. DC3000] MNKNGMRPVHPGEVLKEEYLEPMGLTAAALARALKVSTPTVNDIVLQRRGVSADVALRLA VCLETSPEFWLNLQLAYDLR KAETEKGAQIREQVKCLAHCA >gi|28867445|ref|NP_790064. 1| proteic killer protein, [Pseudomonas syringae pv. to- mato str. DC3000] MIVSFKCVHTRYLFLQGKTRLWPSIKSVAERKLAMLDAATSILDLRSPPGNRLEALDGSR SGQYSVRINAPFRICFVWSI NGPEDVEIVDYH NGPEDVEIVDYH >gi|28867652|ref|NP_790271. 1| virulence-associated protein, [Pseudomonas syringae pv. tomato str. DC3000] MEMFNPPHPGEILLEEVIPGLQTTITEFASHLGFARETLSRILHGHAPVSPDLAVRLERA GISSARLWLGIQADYDLWQA EHREQPPIEPYVIANPG >gi|28867653|ref|NP_790272. 1| proteic killer protein, [Pseudomonas syringae pv. to- mato str. DC3000] MIVSWRHKGLKAFFETGSSSGIRADHSKRLAHVLAVLNRARTPANVNMPGWRLHPLKGEL EGFWSITINANWRIIFRFFD TDVELVDYLDYH The following sequences were found later, in a supplementary search: >gi|29349640|ref|NP_813143. 1| Hypothetical protein BT4232 [Bacteroides thetaiotaomi- cron VPI-5482] MNIMQVNPDVGSMDAVLDKLYGKVGTNKSYISRIEKGALEPGVGLFFRIIDALGLKVEIV KPMI >higB|29345410 : 5572334-5572546, length 71, Bacteroides_thetaiotaomicron_VPI_5482, higB MLAGGCGGWLKGLKRLKIKKHSMNIYGAFFIFDEGNIVMLFNGFQKKTQKTPESEIEKAV KLKNEYYASKP >gi|29350141|ref|NP_813644. 11 Hypothetical protein BT4732 [Bacteroides thetaiotaomi- cron VPI-5482] MEAKTNEEFFNVSALIDERFGKEGTASRAEAEEKAYAFYTGQIIEDARKKAKITQAELAR RIGSDRSYISRVESGQTEPK VSTFYRIMNALGCKIEFSMIL >gi 29350140refNP813643. 1 Hypothetical protein BT4732 [Bacteroides thetaiotaomi- cron VPI-5482] MKREIIAYKGYFKEFFENLDAGTQDKILYVLMLLQTQDRIPLKFMRLIEEGLYELRIEYQ SNIYRIFFCFDEGRIVILFN GFQKKTEKTPKKEIDKKILRKEYYGSKNK GFQKKTEKTPKKEIDKAKILRKEYYGSKNK >higA127375111 : 5539812-5540207, length 132, Bradyrhizobium_japonicum, HigA MTTQKPVWWIGSSKDDLRAFPDEVRRVMGFAINDAQNGDEHPRAKALKGFGGRSVLEVID DEDGDTFRAVYTVRFAGVIYVLHAFQKKSKKGIETPKHDILVIQARLKAAEAHYQENYGK GGKK >gi|27380106|ref|NP_771635. 1| blr4995 [Bradyrhizobium japonicum USDA 110] MRWEARVTKTYRPVTPSQLADELNQAFASAEPHTISRAIGQALKDFNISEISKKAELQRT SIYRAFGNEQLPNFSTVLGV LTAMGLQLKVAPKRGGHASF >higB|27375111 : 1797159-1797353, length 65, Bradyrhizobium_japonicum, HigB MLTAARLIRAPSLMKFYSTSGSLRPRLQKRWDSRQHLHDILAEKKPVSPNVAARIGKPVG NGPAI >higA|27375111 : 1796750-1797079, length 110, Bradyrhizobium_japonicum, HigA MTTTRIGRSQRLAISCDLRQYGRATSGEPAASTRECTSASRSHPDCRAIGVRLDTLNEAV NSSELKLTGNDFHKLAGKSVRYTIHINGPWCITFEFEGGDAFKVDFEQYH

------------------------------------------------------------ ------- >gi|27377225|ref|NP_768754. 1| blr2ll4 [Bradyrhizobium japonicum USDA 110] MSKAIKATAGSDNIFADLGFANPEEELLKAKLIRELRAIIKRRKLTQTKAAELLGLKQPD VSALVTGRVGKFSIDRIVRC LDRLNYRVDWIRHKPVRRASSRAAA >higBi27375111 : 2290771-2291367, length 124, Bradyrhizobium_japonicum, corrected start HigB MDRIGEWDGQWRKFAIYRPVRKPLQNYSSSAIREGR MTTQKPWWIGSSKDDLRAFPDEVRRVMGFAINDAQNGDEHPR AKALKGFGGRSVLEVIDDEDGDTFRAVYTVRFAGVIYVLHAFQKKSKKGIETPKHDILVI QARLKAAEAHYQENYGKGGK K K >gi] 16127267ref NP421831. 1 hypothetical protein CC3037 [Caulobacter crescentus CB15] MVTLSRFDPVEMIDNAEAVAVFLADAFDTGDADYIQHMLGLIARSKGMAEVAEKAGLGRE SLYKALKDGASPRFDTILRV VHALNLKLALVSATEANSAEDADDEAAA >gi|16127268|ref|NP_421832. 1| hypothetical protein CC3037 [Caulobacter crescentus CB15] CB15] MRGLPGDLRPVGGGVSELRVHVGPGYRIYVARRADWIVLLCGGDKSSQARDIEKARVIAR SLEW >gi|25029304|ref|NP_739358. 1| hypothetical protein CE2747 [Corynebacterium efficiens YS-314] MNTNTETFAPFDTANHLNTVEDVAAYLEAVIEDSDSDDDSTVIAQALGAIARSRNFSQIA RQAGMSREGLYKALSADGNP SLATVIKVSHALGLRLRFEATA >gi|25029303|ref|NP_739357. 11 hypothetical protein CE2747 [Corynebacterium efficiens YS-314] MVEIVASATFDRWLRKLIQNRRAAARALVRIDRLAANNPGDVKPVGGGISELRIDYGPGC RVYFLRERDRLVLLLTGGDKS TQETDIKAAHAIADIWRRTQGVHE TQETDIKAAHAIADIMRRTQGVHE >gi|29654981|ref|NP_820673. 11 Hypothetical protein CBU1691 [Coxiella burnetii RSA 493] MIISLDGQEGIARFFYCTQVKKEIVILHAFIKKTQETPIKELEIAKKRMKEVKNND >gi|29654980|ref|NP_820672. 1| DNA-binding protein, putative [Coxiella burnetii RSA 493] MTRRSTTWHKTFKQTGLSDPEAKAEYEAFKLQLELADQLKKERQKAHLTQETVAERMETQ KPWARIEAAGGKGRHSPSL KTLVKYANAIGCHLQIKLVSSKKRKGAR KTLVKYANAIGCHLQIKLVSSKKRKGAR >gi26250653refNP_756693. 1 Hypothetical protein c4838 [Escherichia coli CFT073] MDKALFERLTHSMAQMNEIIEGTRQPSRTFEVDAMKIKEIRRASGLSQSKFADLISVSVD TLRNWEQGRRSPTGPAKALL RAIANDPQHVLQALNR >gi|26250652|ref|NP_756692. 1| Hypothetical protein c4837 [Escherichia coli CFT073] MLFIETEIFTEDVQKLLNDDEFSRFQFFLALNPDYGEVIPETGGLRKVRWVSGGKGKRAG VRVIYFHQVKHYEIRLLLIY RKGIKDDLSPQEKAMLRLLNTRW >gi|26251283|ref|NP_757323. 1| Hypothetical protein c5477 [Escherichia coli CFT073] MSFFDELKTSLEEAVEIKQGLKEPARVTRYEIADVKAIREQLNVSQSEMAKALGTSVDTI KSWESKRRNPTGLAAKVLAT IKENPAFFRELASH >gi|26251282|ref|NP_757322. 11 Hypothetical protein c5476 [Escherichia coli CFT073] MLSGITDLKVYLVLHLGVQCTCQGGGMGKAIIFIETPMFTRQIKQIATDDELKELQKELI GTPDKGDLIQQTGGLRKVRM AAGSQGKSGSVRIIYFLATEEIIYLIMAYPINAKDSLTDTEKAQLKKLTKLLKGEI ------------------------------------------------------------ ------- >gi|15802545|ref|NP_288571. 1| Z3231 gene product [Escherichia coli 0157 : H7 EDL933] MKIETFDSVWDAVSDTPEQAENMRIRAELVTIINNWIEQQGFSQAQAASALGVTQPRISE LARGKIQIFSIDKLITMMAH AGLHIQRIEVQYPHAA >gi|15802544|ref|NP_288570. 1| Z3230 gene product [Escherichia coli 0157 : H7 EDL933] MRKKLAFLDTSLDDLRAFPESSRQEIGYQLDRIQQGLNPYDWKPFSTIGPGVREIRTRDA DGIYRVMYVAKFEEAVYVLH CFQKKTQTTSQSDIDLAKRRYKELVQERKNEN CFQKKTQTTSQSDIDLAKRRYKELVQERKNEN >gi|15832124|ref|NP_310897. 11 hypothetical protein ECs2869 [Escherichia coli 0157 : H7] MKIETFDSVWDAVSDTPEQAENMRIRAELVTIINNWIEQQGFSQAQAASALGVTQPRISE LARGKIQIFSIDKLITMMAH

AGLHIQRIEVQYPHAA >gi|15832123|ref|NP_310896. 1| hypothetical protein ECs2869 [Escherichia coli 0157 : H7] MRKKLAFLDTSLDDLRAFPESSRQEIGYQLDRIQQGLNPYDWKPFSTIGPGVREIRTRDA DGIYRVMYVAKFEEAVYVLH CFQKKTQTTSQSDIDLAKRRYKELVQERKNEN >gi|16272602|ref|NP_438819. 11 Hypothetical protein HI0660 [Haemophilus influenzae Rd KW20] MNKISPLGSNWNEFEQQIFNEEEIRESNLRVALIKELITSRQQLGISQKQLETLSGVKQP MIARIEKGQTNPQLETLLKL LAPLGKTLSIVPLRVKNA >gi|16272603|ref|NP_438820. 1| Hypothetical protein HI0660 [Haemophilus influenzae Rd KW20] MYEILFYRDQNDIEPVKEYLLSLAQNESKDSRIKLNKIRDYVKLLSELGTSVGKPYVKHL DGEIWELRPIRDRILFARLM DGRFVLLHQFMKKTQKTPKREIQTAQQRLSELKERLKNE >gi|16273326|ref|NP_439570. 1| Hypothetical protein HI1419 [Haemophilus influenzae Rd KW20] MTEQLKDFDVAEHLTSEEEIQLYLNEILQEDNIELILSALGDIARARNMSQIARDAGISR EGLYKALSGTGNPTFATVMK VMKALNLQFQVQQSRFA >gi|16273325|ref|NP_439569. 11 Hypothetical protein HI1419 [Haemophilus influenzae Rd KW20] MTIQIKTTLTFDSWLSKLKNLRAKAKINARIKRLQFGNFGDIKSVNDGIFELRIDEGQGY RVYLKNQNGVLVILLCGGDK STQDKDIKQAKLLAQELGL STQDKDIKQAKLLAQELGL >higB|13470324 : 4800860-4801012, length 55, Mesorhizobiumloti, higB MTGEMTSGNVFADLGFDNSEEELSKAKLAVRSAPSLCVGASLKRNRLNCLL >higA|13470324 : 4800572-4800853, length 94, Mesorhizobium_loti, higA MSASSWVLQSTMPKMASSILGVKALKRFGGRILAWDDLDRILIARPCRRFAGVICIFAS RRRAGTRPSAKSISLQRLKVAGTHDRENYGKGHD RRRAGTRPSAKSTSLQRLKVAGTHDRENYGKGHD >gi|15841426|ref|NP_336463. 11 DNA-binding protein, putative [Mycobacterium tuberculo- sis CDC1551] MSIDFPLGDDLAGYIAEAIAADPSFKGTLEDAEEARRLVDALIALRKHCQLSQVEVAKRM GVRQPTVSGFEKEPSDPKLS TLQRYARALDARLRLVLEVPTLREVPTWHRLSSYRGSARDHQVRVGADKEILMQTNWARH ISVRQVEVA >higB|15839372 : 2199074-2199424, length 117, corrected start, M. tuberculosis_CDC1551, HigB HigB MGTAKFFRASVDGRPVFKKEFDKLPDQARAATKIVLMQRYLVGDLAAGSIKPIRGDILEL R WHEANNHFRVLFFRNGQHPVALTAFYKNQQKTPKTKIETALDRQKIMKRAFGDTPPI >gi|15609093|ref|NP_216472. 1| hypothetical protein Rv1956 [Mycobacterium tuberculosis H37Rv] MSIDFPLGDDLAGYIAEAIAADPSFKGTLEDAEEARRLVDALIALRKHCQLSQVEVAKRM GVRQPTVSGFEKEPSDPKLS TLQRYARALDARLRLVLEVPTLREVPTWHRLSSYRGSARDHQVRVGADKEILMQTNWARH ISVRQVEVA >higB|15607142 : 2201741-2202091, corrected start, length 117, M. tuberculosis_H37RV, HigB HigB MGTWNNFFRASVDGRPVFKKEFDKLPDQARAALIVLMQRYLVGDLAAGSIKPIRGDILEL R WHEANNHFRVLFFRWGQHPVALTAFYKNQQKTPKTKIETALDRQKINKRAFGDTPPI >gi|30249348|ref|NP_841418. 1| Helix-turn-helix motif [Nitrosomonas europaea ATCC 19718] MEKITDSSGNIFTDLGFNPEQSAIYTLRAELMSNLRKTIRERKWTQEEAAKVLNIGQSRV SDLMRGKWEKFSLDMLITLA IRVGKRIGITW >gi|30249347|ref|NP_841417. 11 phage-related protein [Nitrosomonas europaea ATCC 19718] 19718] MPSDFKPMLAVGPGAYEIRIHIMGEWRVIYVAKMQDTIYVLHTFQKKTQKTSKHDRYRQT TKEITNGKNN >gi|30249334|ref|NP_841404. 11 Cro repressor helix-turn-helix motif : Helix-turn-helix motif [Nitrosomonas europaea ATCC 19718] MSKKTPLNEIAEFDVSDYLRDDEDIAEYLTQVLAEGDSNELLRAIGYIAKARGITQLAKD TGLGRESLYKAFRAGSKPQF ETVFKVLHALNINLKAIPKEWSTRV

>gil30249335lreflNp-84l405. ll Hypothetical protein NE1356 [Nitrosomonas europaea ATCC 19718] MVYSLGYKTMYIVKRLDEFDKWLDGLKDRPTRIRLIRRLDKARQGLLGDVKSVGEGVFEM REFFGSGWRMYYIQQGGTII LMLGGGDKSTQSKDIQKAIQLANDLGENSYE LNLGGGDKSTQSKDIQKAIQLAMDLGENSYE >higA|30248031 : cll56304-1156630, length 109, Nitrosomonas_europaea, higA MRPLTNYQTINDVDGRPAFWIPYADFVHSQVYVPKDGAPHAWSKAINGMSMLQAWREY LMLTQEEMAKRMEITQAGYAQIEAAKRPRKATLEKAAAAMGITLEQLAY >higB|30248031 : cll56617-1156871, length 85, Nitrosomonas_europaea, higB, also hits into relE MNRIIWKTKAIKQVLKLPRQTAQVIRDTVEEKLSVFPDCNSIKKLTNHRYPYRLRAGDYR VFFDFDGEIHIINIQEVKKRDETTY VFFDFDGEIHIINIQEVKKRDETTY >gi|17228528|ref|NP_485076. 1| unknown protein [Nostoc sp. PCC 7120] MTQEPVFEESSGNVFADLGLSNASELFTRGKIGIQVLHLLKQRNLKQREISELLGIPQSE VSHLMKGEFQRFSEGKLLIF LKRLDTEITLHLRPRHAPDQAAEIVISL >gi|17228529|ref|NP_485077. 1| hypothetical protein [Nostoc sp. PCC 7120] MDDEDITEIPLRPLVWMGDSLKNIRSFPEEVRASVGYALQLVQAGETPMDAKPFKGVGSG VYEIVKRYDTDTYRAVYAVK IGEKIYVLHAFQKKSKQGIKTPLADVDLIKQRYKDAVAREKQE >gi) l7229893jrefNP486441. 1 hypothetical protein [Nostoc sp. PCC 7120] MMPRSTSYHEKLIQDLQNPLEAAAYIEVILEEGDPKMLSKALQNVIEAHGGVDQLSTPVK ELYNKLDQMLSDKGEIEFYS LNSLLDALGLHLAVTVKP >gi|17229894|ref|NP_486442. 1| hypothetical protein [Nostoc sp. PCC 7120] MEVQPKEIRNYLRLDGIDIFSDWFDSLRDRKAKAKIRARLDRVENGNLGDCKSVGDGVFE LRIDYGSGYRIYFGQEGLTI IILLCGGDKSTQDKDIAKAKEYWEDYRSRDDA IILLCGGDKSTQDKDIAKAKEYNEDYRSRDDA >higA|26986745 : cl418120-1418494, length 125, Pseudomonas_putida_KT2440, HigA MFAFHNEKAPESFRFQGLDLVWRRDRDLNPRYCCQYNGFRIRPVRPLRHLSNAAHHTSVL LKRKSFFQKNRWSGACVNVPLTAARPGAWQLLRRLRSRRPGPGGSGPCPSSCGFPCPTG GSRPG >gi|26987976|ref|NP_743401. 11 hypothetical protein PP1241 [Pseudomonas putida KT2440] MISKKISPQDMPILDLDLSKTKRFEASRFLDSPETIAAFLAEAMKANDAQTLMHALGEVA KAKGVNQFAQDAGVNRESLY KTLKGEEKTRFTTIQKLMVALGVELTVRPLEKLPGS KTLKGEEKTRFTTIQKLMVALGVELTVRPLEKLPGS >higA|26986745 : 334364-334672, length 103, PseudomonasputidaKT2440, HigA MRSSWHPCRPQYCISPWLRRIQYGQDPERPIKSLTESVGAGAIELIINGSPAFRCVYVAK FADMVVVLHSFVKTTNRSERHAMQVAEQRMKELKQELRKMGYRV >higB|26986745 : 334049-334360, length 104, Pseudomonas_putida_KT2440, HigB MPGVWVITIWIGEPASFEGRVRWRKPSLSSMSIMASKVNFSILPFASSDMRDWVTFSLA AASCCLRPIFLMQSVMKMDKSIFKAILLAVSASWVAWKGLSWN >gi|28872483|ref|NP_795102. 1| hypothetical protein PSPT05375 [Pseudomonas syringae pv. tomato str. DC3000] MTTHTRSHDESVLDMLREDEAFAIEYLSVALEEIDEDGGEDAFLIAIRRLIEARGGMGNL SKNTGLARPNLYRSIAAGGD PKLSTILKVLQALGVGMSKWSHRPDVGGQRTDP >gi|28872482|ref|NP_795101. 1| hypothetical protein PSPT05375 [Pseudomonas syringae pv. tomato str. DC3000] MYEVEHVLSANGVDIYQGWLDTVRDTRSKARITTRVDRAALGHFGITEPVGDGVFEMKLD FGPGFRVYYAIEGQKVLFLL GGGSKDKQQNDIDQAKALWKCHKVKKK GGGSKDICQQNDIDQAKAI, WKCHKVICKK >gi|15893146|ref|NP_360860. 11 hypothetical protein RC1223 [Rickettsia conorii str. Malish 7] MPVFLITGFIKSKMENINHNSCNELKKLTEELENYMSDEAKINNKNTNQTDKSILIGMQE AVLYTKGKLKANKHDIKLSN IDVHEARDKLKLTQQQFATTFGVSVATLRNWEQGRRLPTGAAKLLLKIIEKEPNWVKRVL RG >gi|15893145|ref|NP_360859. 1| hypothetical protein RC1222 [Rickettsia conorii str. Malish 7] MILNKNYLLILLRQWRIIIMSKKLISWELPEFQKFAQNNLNKKECFEIIHYIAANPDQGD IIKGTGGIRRKLRFTYK ------------------------------------------------------------ -------

>gi1167622241reflNP_457841. 11 hypothetical protein STY3651 [Salmonella enterica subsp. enterica serovar Typhi str. CT18] MIAKTDSDFRHVTPSGGNVFADLGFHKQDAEKFYADSLNEIENTLAIKQQLMEEITLWIT QNQMKQAEVATVLHISRPRV SDWNKKCSKFTIDALVNMLSRIGKPVRVMVGP >gi|16762225|ref|NP_457842. 11 hypothetical protein STY3651 [Salmonella enterica subsp. enterica serovar Typhi str. CT18] MLLTRALSNEKEIRWVGSSLEDLLAFPITVRKAVGYQLHKIQYGIEPDDWKPFSEIGAGV NEIRIRNNNGIYRVMYVANF AEALYVLHSFQKQTQQTSQHDKNIARTRYNRWQQRRNSL AEALYVLHSFQKQTQQTSQHDKNIARTRYNRWQQRRNSL >gi16767183IrefINP_462798. 1 putative cytoplasmic protein [Salmonella typhimurium LT2] MIAKTDSDIRHVTPSGGNVFADLGFHKQDAEKFYADSLNEIENTLAIKQQLMEEITLWIT QNQMKQAEVATVLHISRPRV SDWNKKCSKFTIDALVNMLSRIGKPVRVMVGP >gi|16767182|ref|NP_462797. 1| putative cytoplasmic protein [Salmonella typhimurium LT2] MGSSLEDLLAFPITVRKAVGYQLHKIQYGIEPDDWKPFSEIGAGVNEIRIRDNNGIYRVM YVAKFEEALYVLHSFQKQTQ QTSQHDKNIARTRYNRWQQRRNSL QTSQHDKNIARTRYNRWQQRRNSL >higA|16763390 : 4241636-4241944, length 96, Salmonella_typhimurium LT2, HigA MDKVLFERLTQSMSQMNEIIEGTREPSRTFHIDAMKIKEIRQASGLSQSKFAELISVNVD TLRNWEQGRRSPTGPAKALLRAIANDPRNVIQALRY >higB|16763390 : 4241948-4242235, length 103, Salmonellatyphimurium-LT2, HigB MQFIETELFTEDVKKLLDDDEYHKLQVFMAQHPDCGDVIQETGGLRKMRWGARGKGKRSG VRIIYFHRSQRYEIRLLLIYQKGIKDDLTPQEKAVLRMLNERW >gi29143713refNP807055. 1 Hypothetical protein t3392 [Salmonella enterica subsp. enterica serovar Typhi Ty2] MIAKTDSDFRHVTPSGGNVFADLGFHKQDAEKFYADSLNEIENTLAIKQQLMEEITLWIT QNQMKQAEVATVLHISRPRV SDWNKKCSKFTIDALVNMLSRIGKPVRVMVGP >gi|29143714|ref|NP_807056. 1| Hypothetical protein t3392 [Salmonella enterica subsp. enterica serovar Typhi Ty2] MLLTRALSNEKEIRWVGSSLEDLLAFPITVRKAVGYQLHKIQYGIEPDDWKPFSEIGAGV NEIRIRNNNGIYRVMYVANF AEALYVLHSFQKQTQQTSQHDKNIARTRYNRWQQRRNSL AEALYVLHSFQKQTQQTSQHDKNIARTRYNRWQQRRNSL >gi|15965583|ref|NP_385936. 1| HYPOTHETICAL PROTEIN SMc00177 [Sinorhizobium meliloti 1021] MGFPGLVGFRGAAASRSAWLALAAILAGCGSRQAANDTFSLASVPAVERPGATNRQLLVP EPTALKTLGSDQIVVRLSR SELQYLARAQWGDSLPRMVQDRLVQTFDNTGRIRVGKPGQGLAIDYQLITELRAFEISTD GAATAWEIFAKILDDRNGT VRKQQAFRAWPVRGAGNPAFVAALDAAFARVAADIVGWTLSSI >gi|15965582|ref|NP_385935. 1| HYPOTHETICAL PROTEIN SMc00178 [Sinorhizobium meliloti 1021] MIRMLQSATFRKWHSKLRDERAKAAIARRLLRLAQVNPGDVSPVGEGISELRIHHGPGYR VYFQKRGELIMLLLCAGDRA HRIETSERRKRSPPNGVISMSEKFTEFDVSDLLTSERAIEAFLTEAMETGDAQHIASALG AVARVKGMTKIARETGLARE HLYRSLSENGNPTLETTLAVLKTFGFHLMPKHDAAV >gi|15901010|ref|NP_345614. 1| hypothetical protein SP1143 [Streptococcus pneumoniae TIGR4] MKNNAIGSNWKDVRAELFSKEEILESDMRVAIMSELIEARNEKGISQKKLEEMSGVSQPV IARMETGKTSPQLDTVLKVL ASLGKTLAWPLEHEQV >gi|15901009|ref|NP_345613. 1| hypothetical protein SP1143 [Streptococcus pneumoniae TIGR4] TIGR4] DGSFVLLHHFMKRTQKTPKREIEQAKRELADLKERGLDNEK DGSFVLLHHFMKPTQICTPKREIEQAKRELADLKERGLDNEK >higA|16329170 : c474208-474432, length 75, Synechocystis PCC6803, HigA MNTAQISTDGTHQIVILPENFTIAGSEVYIKKIGSTIILIAKNNPWQSLIESLDQFSDDF MKTREQPPLDIREEF >higB|16329170 : c474514-474792, length 92, Synechocystis_PCC6803, HigB MKIAWSPKSLRSFKRLIPKNPNLRPMIEQILHQLATDPFHPSLRTHKLKGELANVWSCSI D YNYRLLFEFVNNPEDKEEAILLLNLGSHDEVY

>gi|15837156|ref|NP_297844. 11 hypothetical protein XF0554 [Xylella fastidiosa 9a5c] MLNRRECGAAVEVAARRHLERAGLRWLASNVCFRGGELDLVMYDVMSVVFVEVRYRQQEN HGSAAQSVDRRKRRKLVMAA QLFLQRHPFLAQVPCRFDWEGAGRPLQLHWIRDAFRLDDC >higB|15836605 : c527947-528210, length 88, Xylellafastidiosachr, higB MKVLRFLGDSLMCLRQFPEDACSDAGYQLDKIQRGEQPKDFKPMPSIGKGVEELRIWDDS GTYRVVYTARLADAVYVLHAFQKKTQATSKRDVELAKRRYTELTKGAK ------------------------------------------------------------ ------- >gi|15838173|ref|NP_298861. 1| hypothetical protein XF1573 [Xylella fastidiosa 9a5c] MSNERFTSVWDAIEDTPEAAENMKLRSALMMALKQHIETAALSQSQAATLFGVTQPRVSD LMRGKINLFGLDALVNMAAA AGMHVEMRVLKAA >gi|15838174|ref|NP_298862. 1| phage-related protein [Xylella fastidiosa 9a5c] MVGPKPIEFRGSALDDLRAFPVSVRREAGYQLHQVQNGRDPDDWKPMPTVGRGVREIRIR DADGAFRVIYVAKLSEAVYV LHCFQKKTEKTTKGDLDVAAKRYRDLFNEVGQ >gi|15838197|ref|NP_298885. 11 hypothetical protein XF1596 [Xylella fastidiosa 9a5c] MTMTEKLTSYDPAEDLTTDQAIADFMAAAFGTNDPAYVAHALGWARAKGMTQIASQTGLS REQLYRSFSAEGNPTLRTT LAVMKALGIELSAKPSGVH >gi|15838198|ref|NP_298886. 1| hypothetical protein XF1596 [Xylella fastidiosa 9a5c] MIELKQTDTFRKWREKLKDARARSAIASRLDRLAFGHVGDAEPVGKGVSELRINYGPGYR VYFQQRGDTIYLLLCGGDKG LQARDIKTALHLSEQWSE LQARDIKTALHLSEQNSE >gi|15838278|ref|NP_298966. 1| hypothetical protein XF1678 [Xylella fastidiosa 9a5c] MSNERFTSVWDAIEDTPEAAENMKLRSALMMALKQHIETAALSQSQAATLFGVTQPRVSD LMRGKINLFGLDALVNMAAA AGMHVEMRVLKAA >gi|15838279|ref|NP_298967. 1| phage-related protein [Xylella fastidiosa 9a5c] MVGPKPIEFRGSALDDLRAFPVSVRREAGYQLHQVQNGRDPDDWKPMPTVGRGVREIRIR DADGAFRVIYVAKLSEAVYV LHCFQKKTEKTTKGDLDVAAKRYRDLFNEVGQ >gi|15838303|ref|NP_298991. 1| hypothetical protein XF1703 [Xylella fastidiosa 9a5c] MNNETFSRYDTADYLKTEEDIAAYMEAVMEEGGRDNPAFIARALGAVARARNLSQLARDV GMSRQGLDKALSNDGNPSFS TILKVAKALGLRMSFTPSSMS >gi|15838304|ref|NP_298992. 1| hypothetical protein XF1703 [Xylella fastidiosa 9a5c] MHMVELIKTSTFDAWINSLRDRKAAARIQARLDRLALGNPGDVKPVGAGISEMRIDHGPG YRIYFMKHGAVLILLLCGGD KSSQMRDIEQAKALAALWKDEP >gi|15839352|ref|NP_300040. 1| hypothetical protein XF2763 [Xylella fastidiosa 9a5c] MTITKKINVSELPEFDAAEYLSSEEEVAAYLTAVLEENDPALLAAALGDIARSRGMSQIA KDSGITREGLYKALRPGSEP RFDTISRVCTALGIRLVAQPMR >gi|15839353|ref|NP_300041. 1| hypothetical protein XF2764 [Xylella fastidiosa 9a5c] MTLLQSNRLITVQCMIYTVKRLEEFSDWLKGLKDGLARQRLIKRLRKVQLGNFGDVQPVG EGVFEMREHFGPGWRMYYVQ RGSFLIVMLGGGDKSTQQSDIRRAIELAKSLED RGSFLIVMLGGGDKSTQQSDIRRAIELAKSLED >higA|28197945 : 1167816-1168139, length 108, Xylella_fastidiosa_Temeculal, higA MKVLRFLGDSLMCLRQFPEDACSDAGYQLDKIQRGEQPKDFKPMPSIGKGVEELRIWDDS GTYRWYTARLADAVYVLHAFQKKTQATSKRDVELAKRRYTELTKGAK >gi|28198867|ref|NP_779181. 11 Hypothetical protein PD0967 [Xylella fastidiosa Temec- ulal] MTKIETFNSVWDALADTPEQAANLRARAELMRQIAAVIEANDWNQSQAATHCGVTQPRIN DLLRGRISRFSLDALVNIAT AIGRRVHVKLEAA AIGRRVHVKLEAA >gi|28199067|ref|NP_779381. 11 Hypothetical protein PD1177 [Xylella fastidiosa Temec- ulal] MNNETFSRYDTADYLKTEEDIAAYMEAVMEEGGRDNPAFIARALGAVARARNLSQLARDV GMSRQGLDKALSNDGNPSFS TILKVAKALGLRMSFTPSSMS >gi|28199066|ref|NP_779380. 1| phage-related protein [Xylella fastidiosa Temeculal] MHMVELIKTSTFDAWINSLRDRKAAARIQARLDRLALGNPGDVKPVGAGISEMRIDHGPG YRIYFMKHGAVLILLLCGGD KSSQVRDIEQAKALAALWKD KSSQVRDIEQAKALAALMKD

>higA|16120353 : c964230-964379, length 50, Yersinia_pestis_C092_chr., HigA MDNKRQPPSLSHEQWARMLKKPAVRAEYERLERQDFAIIDETLKGIHSE >gi|16121186|ref|NP_404499. 11 hypothetical protein YP00879 [Yersinia pestis C092] MNYTIEYYDDDVITQLLAQPISLQANFISLAKRMKRYGIKMVDAVPMHYHEDVFELCFYE PKGWNRVIFMAQIDWQIVIL HIWQKTAYMPWKEKGKAAKRMKELRFG >gi|16121389|ref|NP_404702. 11 putative DNA-binding prophage protein [Yersinia pestis] MIMAKARLHDDAMVQLLMEDPEFAQVYLHQALLDIDEEGGQEAFLMALRHWEARGGMASV AKKAGVSRETLYRTLSPSG NPTLKTLLSWSATGFQFSHLASITA >gi|16121388|ref|NP_404701. 11 putative prophage protein [Yersinia pestis] MMKTIKHYLTPEGRDLYMEYLKSLRDSIAKAKISSRVNRIASGNFGDHKPCREGVWELRI DQGPGYRVYYSLVAVKSCCC FWAVISARRMPTSIRLLCVLKII FNAVISARRMPTSIRLLCVLKII >giI16122544refNP_405857. 11 putative DNA-binding phage-related protein [Yersinia pestis] MKKTDDFDIIPFAWVKAAALSHPQVNDAYTDLQIRQAMMTELKAARQQCNLTQEEVALRA GLKKQNISRMEKGIISPNLT TLSRYAAALGGTFVFQFNPNSSYATKE >gi|16122545|ref|NP_405858. 1| putative phage protein [Yersinia pestis] MLRLAQRELVRLPVGIQAVLIKAMDELEACGHELREPYVRDMGQGLKELRVSAKEGIGRG FFFCHLHRQVYIIHLLQKKT QKTPRRTLILAYRRMKELKRRLQS QKTPRRTLILAYRRMKELKRRLQS >gi|16123631|ref|NP_406944. 11 putative transcriptional regulatory protein [Yersinia pestis] MKSDLTLHAWDEVRAELLQDEETARAYAIVMLRKALLNSLVAVRKSKQLTQVDIAKRIGV SRQAISKFEKGESAPTLDTL IGYTAAMDIDFAANMKKIFTQTF >gi|16123632|ref|NP_406945. 1| hypothetical protein YP03486 [Yersinia pestis C092] MGRDDQNHKRRKNFPIRLLGSARKELSDLDAINRAEFLVAIDVFELHGPGSGVPNVEKIG GDMYELKTHSRSHWLRGFYF HYVDGLYIVTHIFAKKTNKAPDSSKALGLRRYKDFLRSQGEE HYVDGLYIVTHIFAKKTNKAPDSSKALGLRRYKDFLRSQGEE >gi|22124613|ref|NP_668036. 1| Hypothetical protein y0699 [Yersinia pestis KIM] MKSDLTLHAWDEVRAELLQDEETARAYAIVMLRKALLNSLVAVRKSKQLTQVDIAKRIGV SRQAISKFEKGESAPTLDTL IGYTAAMDIDFAANMKKIFTQTF >gi|22124612|ref|NP 668035. 1| Hypothetical protein y0698 [Yersinia pestis KIM] MGRDDQNHKRRKNFPIRLLGSARKELSDLDAINRAEFLVAIDVFELHGPGSGVPNVEKIG GDMYELKTHSRSHWLRGFYF HYVDGLYIVTHIFAKKTNXAPDSSKALGLRRYKDFLRSQGEE HYVDGLYIVTHIFAKKTNKAPDSSKALGLRRYKDFLRSQGEE >gi|22125904|ref|NP_669327. 1| Hypothetical protein y2012 [Yersinia pestis KIM] MKKTDDFDIIPFAWKAAALSHPQVNDAYTDLQIRQAMMTELKAARQQCNLTQEEVALRAG LKKQNISRMEKGIISPNLT TLSRYAAALGGTFVFQFNPNSSYATKE >higA122123922 : 2218599-2218967, length 123, Yersinia_pestis_KIM_chr, HigA MVSLIPFFTEQGRLMYKISLLRLAQRELVRLPVGIQAVLIKAMDELEACGHELREPYVRD MGQGLKELRVSAKEGIGRGFFFCHLHRQVYIIHLLQKKTQKTPRRTLILAYRRMKELKRR LQS LQS >higA|22123922 : c3594262-3594411, length 50, Yersinia_pestis_KIM_chr, HigA MDNKRQPPSLSHEQWARMLKKPAVRAEYERLERQDFAIIDETLKGIHSE >higB|22123922 : c3599007-3599264, length 108, YersiniapestisKIMchr, HigB MNYTIEYYDDDVITQLLAQPISLQANFISLAKRMKRYGIKMVDAVPMHYHEDVFELCFYE PKGWNRVIFMAQIDWQIVILHIWQKTAYMPWKEKGKAAKRMKELRFG Homoloques of parDE toxin-antitoxin system polypeptides >giI16124256 : 2971506-2971288, length 73, ParD MMNKPAKPAADDVDDLFGRPLTPAEEDTWFEHNREAIGQLVDEAWAEFERGEYDERSFAE IIAQGVAEHNAKR >gi|16126988|ref|NP_421552. 1| conserved [Caulobacter crescentus CB15] MGRVIRTRPVSGDLDRVFRDVCENNGVKVASAQLNRIESVFHRLSAFPRLGRDRSDLRPG LRTFSVKPWQVLYRLNGEDV VILRILDGRMNLAAQLGKKT

-------------------------------------7---------------------- --------------- >gi|15595198 : 796960-797238, length 93, ParD MFPQQWRYRLMRVETISYLKRHAADLDLSEPMWTQNGVPAYWESYAERKQRDEAIALV KLLAIGSRQYAEGKHRSVDDLKARLSRRFAQPE >gi15595926) refNP249420. 1 [Pseudomonas aeruginosa PA01] MSPWIRFTDTAEQSIEDQVHHLAPFQGEQAALQSVLSLLDEIEEKISLAPKGYPVSQQAS LLGVLSYRELNTGPYRVFY EFHEEQGEVAVILVLRQKQSVEQQLIRYCLVGPIE >gi|15609097|ref|NP_216476. 1| protein Rv1960c [Mycobacterium tuberculosis H37Rv] MGKNTSFVLDEHYSAFIDGEIAAGRYRSASEVIRSALRLLEDRETQLRALREALEAGERS GSSTPFDFDGFLGRKRADAS RGR >gi|15609096|ref|NP_216475. 1| protein Rv1959c [Mycobacterium tuberculosis H37Rv] MSSRYLLSPAAQAHLEEIWDCTYDRWGVDQAEQYLRELQHAIDRAAANPRIGRACDEIRP GYRKLSAGSHTLFYRVTGEG TIDWRVLHQRMDVDRNL TIDWRVLHQRMDVDRNL >gi|15841430|ref|NP_336467. 1| [Mycobacterium tuberculosis CDC1551] MGKNTSFVLDEHYSAFIDGEIAAGRYRSASEVIRSALRLLEDRETQLRALREALEAGERS GSSTPFDFDGFLGRKRADAS RGR >gi15841429refNP_336466. 1I plasmid stabilization protein ParE [Mycobacterium tu- berculosis CDC1551] MSSRYLLSPAAQAHLEEIWDCTYDRWGVDQAEQYLRELQHAIDRAAANPRIGRACDEIRP GYRKLSAGSHTLFYRVTGEG TIDWRVLHQRMDVDRNL TIDWRVLHQRMDVDRNL >gi|15841634|ref|NP_336671. 11 protein [Mycobacterium tuberculosis CDC1551] MWNRALLASVDALSRDEQIELVEHINGNLAEGMHISEANQALIEARANDTDDAHWSTIDD FDKRIRARLG >gi|15841633|ref|NP_336670. 1| protein [Mycobacterium tuberculosis CDC1551] MTRRLRVHNGVEDDLFEAFSYYADAAPDQIDRLYNLFVDAVTKRIPQAPNAFAPLFKHYR HIYLRPFRYYVAYRTTDEAI DILAVRHGMENPNAVEAEISGRTFE >gi|22536413|ref|NP_687264. 11 [Streptococcus agalactiae 2603V/R] MVTAEKNRAVTFQANKELVSEAMTVLNKKNLTLSSALRLFLQNVWTNEVDLLTEEELEKE KLFKQFQAEINKNIEDVRQ GKFYTSEEVRSELGL >gi|22536412|ref|NP_687263. 1| [Streptococcus agalactiae 2603V/R] MDYKKYQIIYAPDVLEKLKEIRDYISQNYSSTSGQHKMEQIISDIEKLEVFPEVGFDADE KYGSKISKYHSTRGYTLSKD YIVLYHIEEEENRWIDYLLPTRSDYMKLFK >gi|25010297|ref|NP_734692. 1| Unknown [Streptococcus agalactiae NEM316] MVTVEKNRAVTFQANKELVSEAMTVLNKKNLTLSSALRLFLQNVVVTNEVDLLTEEELEK EKLFKQFQAEISKNIEDVRQ GKFYTSEEVRAELGL >gi|25010296|ref|NP_734691. 11 Unknown [Streptococcus agalactiae NEM316] MDYKKYQIIYAPDVLEKLKEIRDYISQNYSSTSGQRKMEQIINDIEKLEVFPEVGFDADE KYGSEISNYHSTRGYTLSKD YIVLYHIEEEENRWIDYLLPTRSDYMKLFK YIVLYHIEEEENRWIDYLLPTRSDYMKLFK >gi|15674648|ref|NP_268822. 11 protein [Streptococcus pyogenes] MSLQKRRITMAKTGTLNLRVDDSVKSAADDILKRLGIPMSTAIDMFLNQIILTGGIPFDV SLPEAPQRVNVDYMSQEKFY DKLITSFEDAKTCNPQDVGKFYFQ >gi|15674649|ref|NP_268823. 11 protein [Streptococcus pyogenes] MKGNCLLKEYQVTMSDDAKADLLSIYHYVRDELCAPQAADDLLERLSQGMLSLSIFPERC AIIEDLIGKGYTFRQLIVKK YRIVYHVLEDEVIIVAWYGSRHMNNW YRIVYHVLEDEVI IVAWYGSRHIINNW >gi|15675733|ref|NP_269907. 1| protein [Streptococcus pyogenes] MTTVKKNRAVTFQANKELVSEAMTVLNKKNLTLSSALRLFLQNVWTNEVDLLTEEELEKE KLFKQFQAEINKNIEDVRQ GKFYTSEEVRAELGL >gi|15675734|ref|NP_269908. 1| protein [Streptococcus pyogenes] MDYKKYQIIYAPDVLEKLKEIRDYISQNYSSTSGQRKMEQIISDIEKLEVFPEVGFDADE KYGSKIIHYHSTKGYTLSKD YIVLYHIEGEENRIVIDYLLPTQSDYIKLFK YIVLYHIEGEENRIVIDYLLPTQSDYIKLFK

>gil2l9O99291refINP-664197-11 protein [Streptococcus pyogenes MGAS315] MAKTGTLNLRVDDSVKSAADDILKRLGIPMSTAIDMFLNQIILTGGIPFDVSLPEAPQRV NVDYMSQEKFYDKLISSFED AKTGNRQDVREFLSQLKENA >gi|21909930|ref|NP_664198. 1| protein [Streptococcus pyogenes MGAS315] MKEYQVTMSDDAKADLLSIYYYVCDELCAPQAADNLLERLSQAMLSLSIFPERCAIIEDL IGKGYTFRQLIVKKYRIVYH VLEDEVIIVAWYGSRHMNNW VLEDEVIIVAWYGSRHMNNW >gi|21911197|ref|NP_665465. 1| protein [Streptococcus pyogenes MGAS315] MTTVKKNRTVTFQANKELVSEAMTVLNKKNLTLSSALRLFLQNVVVTNEVDLLTEEELEK EKLFKQFQAEINKNIEDVRQ GKFYTSEEVRAELGL >gi|21911198|ref|NP_665466. 11 protein [Streptococcus pyogenes MGAS315] MDYKKYQIIYAPDVLEKLKEIRDYISQNYSSTSGQRKMEQIISDIEKLEVFPEVGFDADE KYGSKISHYHSTKGYTLSKD YIVLYHIEGEENRWIDYLLPTQSDYIKLFK >gi|19745671|ref|NP_606807. 1| protein [Streptococcus pyogenes MGAS8232] MAKTGTLNLRVDDSVKSAADDILKRLGIPMSTAIDMFLNQIILTGGIPFDVSLPEAPQRV NVDYMSQEKFYDKLITSFED AKTGNRQDVREFLSQLKENA >gi|19745672|ref|NP_606808. 1| protein [Streptococcus pyogenes MGAS8232] MKEYQVIMSDDAKADLLSIYHYVRDELCAPQAADNLLERLSQAMLSLSIFPERCAIIEDL IGKGYTFRQLIVKKYRIVYH VLEDEVIIVAWYGSRHMNNW VLEDEVIIVAWYGSRHMNNN >gi|19746843|ref|NP_607979. 1| protein [Streptococcus pyogenes MGAS8232] MTTVKKNRSVTFQANKELVSEAMTVLNKKNLTLSSALRLFLQNVVVTNEVDLLTEEELEK EKLFKQFQAEINKNIEDVRQ GKFYTSEEVRAELGL >gi|19746844|ref|NP 607980. 1| protein [Streptococcus pyogenes MGAS8232] MDYKKYQIIYAPDVLEKLKEIRDYISQNYSSTSGQRKMEQIISDIEKLEVFPEVGFDADE KYGSKIIHYHSTKGYTLSKD YIVLYHIEGEENRWIDYLLPTQSDYIKLFK YIVLYHIEGEENRWIDYLLPTQSDYTKLFK >gi|28896373|ref|NP_802723. 1| protein [Streptococcus pyogenes SSI-1] MAKTGTLNLRVDDSVKSAADDILKRLGIPMSTAIDMFLNQIILTGGIPFDVSLPEAPQRV NVDYMSQEKFYDKLISSFED AKTGNRQDVREFLSQLKENA >gi|28896372|ref|NP_802722. 1| protein [Streptococcus pyogenes SSI-1] MKEYQVTMSDDAKADLLSIYYYVCDELCAPQAADNLLERLSQAMLSLSIFPERCAIIEDL IGKGYTFRQLIVKKYRIVYH VLEDEVIIVAWYGSRHMNNW VLEDEVTIVAWYGSRHMNNW >gi|28896571|ref|NP_802921. 1| protein [Streptococcus pyogenes SSI-1] MTTVKKNRTVTFQANKELVSEAMTVLNKKNLTLSSALRLFLQNVVVTNEVDLLTEEELEK EKLFKQFQAEINKNIEDVRQ GKFYTSEEVRAELGL >gi|28896572|ref|NP_802922. 1| protein [Streptococcus pyogenes SSI-1] MNLDYKKYQIIYAPDVLEKLKEIRDYISQNYSSTSGQRKMEQIISDIEKLEVFPEVGFDA DEKYGSKISHYHSTKGYTLS KDYIVLYHIEGEENRWIDYLLPTQSDYIKLFK KDYIVLYHIEGEENRWIDYLLPTQSDYIKLFK >gi|32476300|ref|NP_869294. 11 protein [Pirellula sp.] MFTSNSEHPKMSQHLSPENQAYIDDQVAGGVYTSREEAIDAGIALLRKRNELWQLKESRR QLDEGELVEYDDQTLAARF DELKAKAASRSQM >gi|32476299|ref|NP_869293. 1| protein-transmembrane prediction [Pirellula sp.] MSRYLLSHSANANLDEIAGDASNAVAILEALHNTFQVLANHPGVGTLREDLLPGIRVFSP PRPANNYVIFFYPISGGIEV AAVIHGSRDWISMFTDGFRPKKS AAVIHGSRDMISMFTDGFRPKKS >gi|32473225|ref|NP_866219. 11 protein [Pirellula sp.] MVEYEHGEPNMTVEQAISEISALPPNDQLRIVQAIWDRLPDGVGTDLTESQRAELDRRWA EYKADPTTALSEEEFRERIR IARSR >gi|32473226|ref|NP_866220. 1| protein [Pirellula sp.] MKARLTAHTESDLLRAIDWFDRLSLGLGDKFEAEFYLALERVKVNPESFAPDHTGYRPCR LKRFTAVLYFRIDASDVVVV GLFTSGENERGLQNRR ------------------------------------------------------------ ------------- >gi|16125127|ref|NP_419691. 11 [Caulobacter crescentus CB15]

MASKNTSWLGDHFQAFIDSQVADGRYGSASEVIRAGLRLLEENEAKLAALRAALIEGEES GFIEDFDFDAFIEERSRAS APQGFHEE >gi|16125126|ref|NP_419690. 1| [caulobacter crescentus CB15] MKPYRLSRRAKADLDDIWTYSEQRWGVEQAADYARELQATIEMIAEHPGMGQPDENLRAG YRRCASGSHWFYRVGVRVE IIRVLHQSMNARAHLG IIRVLHQSMNARAHLG >gi|16127215|ref|NP_421779. 11 [Caulobacter crescentus CB15] MPSNGIVRSWRRAMATMNVSLPDAMREWVEGQTQSGRYHNASEYVRDLIRRDQERADKIA HLQRLIDEGLDSGVGERSLH EIRAEARRRAGVDHEL >gi|16127214|ref|NP_421778. 1| [Caulobacter crescentus CB15] MWIMSYRLSRKAEQDLIDIYVAGVGLFGVAQAERYQDTLEAAFGAIAAFPHIGRERPELR PPVRVHPCKSHIILYVLDER GALIVRVRHAGEDWVGEAGG >gi|15888637|ref|NP_354318. 11 AGR_C_2413p [Agrobacterium tumefaciens] MEAPMPTRNVVLTQHHEEIIDDLVKSGRYQNASEVLREGLRLIERRERLEATRLETLKVA AQQGFCDLDQGRYIDVSDDA LDDFISAFGREAEVRLTKSDDK >gil5888638ref) NP354319. l ! AGRC2415p [Agrobacterium tumefaciens] MTTYRLSDAAQSDIIEILGWTHATFGAAARKRYEKLLATALRDVAVDPLRAGTNIRAELG EDVRSYHLRYSRERAKSETG LVKNPRHLLLYRALRPGLVGVGRVLHDSMEIERHLPDDYGDITF LVKNPRHLLLYRALRPGLVGVGRVLHDSNEIERHLPDDYGDITF >gi) l5888836ref) NP354517. lj AGRC2786p [Agrobacterium tumefaciens] MANMTFSLPDPMKDWIESRIQKGEYASASDYVRDLVRRDWARRGQDFSIDELRQIVAESR ASGVGSRSMDDLFAEAERVA TAHGVMRE >gi|15888835|ref|NP_354516. 1| AGR_C_2785p [Agrobacterium tumefaciens] MSCVNNYRLSTQAENEILDIFLYGIERFGLNQARLYKDGMESCFQLLGNNPRMGRSATIV GEGIRRHEHGSHVIFYETDG SGVLILTIVHGRSIRRLKL SGVLILTIVHGRSIRRLKL >gi|17935410|ref|NP_532200. 1| [Agrobacterium tumefaciens str. C58 (U. Washington)] MANMTFSLPDPMKDWIESRIQKGEYASASDYVRDLVRRDWARRGQDFSIDELRQIVAESR ASGVGSRSMDDLFAEAERVA TAHGVMRE >gill79354091refINP-532199. 11 [Agrobacterium tumefaciens str. C58 (U. Washington)] MSTQAENEILDIFLYGIERFGLNQARLYKDGMESCFQLLGNNPRMGRSATIVGEGIRRHE HGSHVIFYETDGSGVLILTI VHGRSIRRLKL VHGRSIRRLKL >gi|13471354|ref|NP_102920. 1| protein [Mesorhizobium loti] MNVSLPDPMKDWVEAQTETGRYANASDYVRDLIRRDQERNDNIAAMQRFVDDGLKSGIGN RSRDALFTEAVKRAGKSPGN G >gi|13471355|ref|NP_102921. 1| unknown protein [Mesorhizobium loti] MGFRLSLAAEEDIIGIAEQGVRLFGAVQARQYHDELFAIFDLIAAGPRMARERLELSPPM RIHPFKAHLWYRIEADGDV FIVRVRHGHEDWANEGTR >gi|13472960|ref|NP_104527. 11 protein [Mesorhizobium loti] MPNYALNEHYERFIRKQLESGRYNNASEWRAGLRMLEDFEAERERWLREEIPGRLTELQQ DPAKGIPADTMFSRLEARH RAKQAKAK >gi|13472959|ref|NP_104526. 11 unknown protein [Mesorhizobium loti] MTEAELEQLYDDIAERASPAIAWNFWGIRDHCLGLSTFPQRGTVRVEIMPGVRIVGYRRA VSIAFAVEGERVLILAIFC AGRNITPELLEDRL AGRNITPELLEDRL >gi|30248282|ref|NP_840352. 11 [Nitrosomonas europaea ATCC 19718] MPIQKNTSVTLGEHFEKFLAHQIEAGRYGSASEAIRAGLRLLEEREAKLEALRRALIEGE QSGPADYSLQNVLDELESAD >gi|30248281|ref|NP_840351. 11 plasmid stabilization element ParE [Nitrosomonas eu- ropaea ATCC 19718] MGSFILRQKAMDDLLSIGRYTRKEWGKTQQIRYLTQLDRAFHELADKPGLGRACDDIREG YFKYGVGKHVIFYRHTGKDQ IEIIRILHGRMDIEQHL IEIIRTLHGRMDIEQHL >gi|30248566|ref|NP_840636. 11 yacA [Plasmid ColIb-P9] [Nitrosomonas europaea ATCC 19718] MSESTFTFRVDEDLKTEFSAAAKDCDRSGAQLLRDYMREFVKTRREVAEHDAWFRKQVQI GLDSANTGNLVPGDEVEAEF

AARRAATRRRLKASE >gi|30248567|ref|NP_840637. 1| [Nitrosomonas europaea ATCC 19718] MMKLFWTPEALQDRDAIYDYIEVDNPRAALALDELFSEKAQRLPDHPALGHPGRVAGTRE LIAHQNYIIIYDVTGELVRV LRVLHAARQWPPSEND LRVLHAARQWPPSEND >gi|30249494|ref|NP_841564. 1| [Nitrosomonas europaea ATCC 19718] MYKLRFFADFCLELTASLTFFRGSLASISCFTADYRYGDMTMATVRKTISLTNQQDAWIT AQVEAGRFTNDSELIRDLIR REQERMAEIDNIRAALIDGEQSGEPQPFDFDQFKRHKLAQHKPG >gi|30249495|ref|NP_841565. 1| plasmid stabilization protein ParE [Nitrosomonas eu- ropaea ATCC 19718] MAEYRLSPAAQRDLDGIFNYTFQQWGAAQAVRYIDILEAACTELVETSSQGQDCSYIRPG YRRRHVERHITTE ------------------------------------------------------------ ------------- >gi|30250055|ref|NP_842125. 1| [Nitrosomonas europaea ATCC 19718] MKAITAKDAKNKFGEMLDTAQREPLTIEKHGRAVAVIMSVQEYQQMKLERLRAKLAAGEE QLDRGEGVEGETFFAELLNE K >gi|30250054|ref|NP_842124. 1| plasmid stabilization protein ParE [Nitrosomonas eu- ropaea ATCC 19718] MKHYLLSPEAKTDITNIRQYTTQQWGKTQADKYILRLRERMRWLADNPMLGRARDEIKEG YRSFSEGDHVIFYRMAGSAI EVIGIPHQNMDIEQNIJSSGNLLLPDIADYEPEDG ElIGIPHQNMDIEQNISSGNLLLPDIADYEPEDG >gi|30249561|ref|NP_841631. 1| protein [Nitrosomonas europaea ATCC 19718] MKVLQSDKAIMMNRKLTELPIDERIQLVEDLWDSIASDQKMLRLTTEQKAELDRRLNAYE VDKNPGRSALEAIAEIRRNL >gi|30249560|ref|NP_841630. 1| [Nitrosomonas europaea ATCC 19718] MTCEVRLRPEAEQDLADAAAWYEEQRQGLGHKFLDEVTTTLSNIAETPLAYPNVHRGTRR AVIRRFPFGIYFQVKKATII WAVMHGSRNPHQWKSRT WAVMHGSRNPHQMKSRT >gi|15829715|ref|NP_308488. 1| protein [Escherichia coli 0157 : H7] MRKITSVSVGEQLDSFITRMVQSGRYGSASEVMRSALRLLEQQESRDEAVRNAVIEGLES GESSMTLRDIAAERKQKHRV >gi|15829716|ref|NP_308489. 1| protein [Escherichia coli 0157 : H7] MYKLSGKAVEDFRGIYDYTLGKFGDEQADRYTDSLGTFLDTLSQMPEIGQDYDAIPEVKK IAFRFHTVYYVIRVDDILIA RILHQLMEPRRHW RILHQLMEPRRHN >gi|15830322|ref|NP_309095. 1| protein [Escherichia coli 0157 : H7] MGTALSPIVSEFETTEQENSYNEWLRTKVTSSLADTRPAIPHDEVMAEMENLIAQIAVTN KSE >gi|15830321|ref|NP_309094. 1| protein [Escherichia coli 0157 : H7] MLPILWLPSARDDLRQIITYIAKENPPAARRLKIRIETSVLPLSEHPYLYPPSERVSGLR EIVTHPNYIILYRVAASSIE IVSVTHSRRQFPFSI IVSVTHSRRQFPFSI >gi|15831534|ref|NP_310307. 1| protein [Escherichia coli 0157 : H7] MPPRLSYKTGGNMNRALSPMVSEFETIEQENSYNEWLRAKVATSLADPRPAIPHDEVERR MAERFAKMRKERSKQ >gi|15831535|ref|NP_310308. 1| protein [Escherichia coli 0157 : H7] MLPVLWLESADTDLDDITSYIARFDIDAAERLWQRLRGCVLPLSEHPYLYPPSDRVPGLR EIVAHPNYIILYRVTTSSVE WNVIHARRQFP WNVIHARRQFP >gi|15800137|ref|NP_286149. 1| unknown [Escherichia coli 0157 : H7 EDL933] MRKITSVSVGEQLDSFITRMVQSGRYGSASEVMRSALRLLEQQESRDEAVRNAVIEGLES GESSMTLRDIAAERKQKHRV >gi|15800138|ref|NP_286150. 1| unknown [Escherichia coli 0157 : H7 EDL933] MYKLSGKAVEDFRGIYDYTLGKFGDEQADRYTDSLGTFLDTLSQMPEIGQDYDAIPEVKK IAFRFHTVYYVIRVDDILIA RILHQLMEPRRHW RILHQLMEPRRHW >gi|29653983|ref|NP_819675. 1| [Coxiella burnetii RSA 493] MKISCRVKPISYLKSNTAEIVRDISETREPMLITQNGEAKLWLDVKSYEEYEETLSLLKI LSLGQKEIEKGQFRSADDV FADLDKD >gi|29653982|ref|NP_819674. 1| conserved domain protein [Coxiella burnetii RSA 493] MNYKWFLQQAQLDLKELKNYMINNFSKRTWCTRYEKIKKIIHTPKLFPDAGSIPPELETL NLNQYRQAISGKNRIIYEL KESIVYIHIICDVRKDMKSLLLRRLFRSESLP KESIVYIHIICDVRKDMKSLLLRRLFRSESLP

>gi|24373020|ref|NP_717062. 11 transcriptional regulator, CopG family [Shewanella oneidensis MR-1] MSTIKPVSVKLDADIKARVEHLAETRKRSSHWMMREAIREYVEREEKREALQQEALRAWE EHQTSGLHVTGDEWSWLES WGSENEQAALHATNSLHCHCIT >gi|24373019|ref|NP_717061. 1| [Shewanella oneidensis MR-1] MPQIVFTATALRDLERLREFLRSKNPPAAQRAASAIINTIRKLESYPDIGRPIDDNDFSF RELLIDFGDTGYLAMYQYDG GERLTVLCIRHQKEAGY GERLTVLCTRHQKEAGY >gi|15601077|ref|NP_232708. 1| protein [Vibrio cholerae] MHTLTANDAKRNFGELLLSAQREPVIISKNSKNTVVVMSIKDFEELEAMKLDYLKHCFES AQKDLDSGKTVDGATFLNTL >gi15601076refNP232707. 1 protein [Vibrio cholerae] MSVYLNMQNKQYKLSQLAQEHLLKIKHYTIENFAEAQWQKYKSTLLSGFQTLADNPGLGK SCEDIYQNGFYFPVGKHMAY YTKEANFILIVAVLGQSQLPQKHLKQSRFVS >gi|15601124|ref|NP_232755. 1| protein [Vibrio cholerae] MFEMAHNARLRGWQRITLNSITTTETTAAQWDWKRHALTVPLEAFVMRALPKMPFDTIIR YFLVFMEMSSWLKIQVSLLV NTSMALLQAKYKVGVTAQQVKSFALRYVYSKTKKPNYSHSVNYLLKESKWTLIMTLIASS MNSIVKTFDETI >giI15601123IrefNP_232754. 1I plasmid stabilization element ParE, [Vibrio cholerae] MKPFNLTVAAKADLRDIALFTQRRWGKEQRNVYLKQFDDSFWLLAENPDIGKSCDEIREG YRKFPQGSHVIFYQQTGSQQ IRvIRILHKsMDvNpIFGA IRVIRILHKSNDVNPIFGA >gi|15601149|ref|NP_232780. 11 protein [Vibrio cholerae] MHTLTANDAKRNFGELLLSAQREPVIISKNSKNTVVVMSIKDFEELEAMKLDYLKHCFES AQKDLDSGKTVDGATFLNTL >gi|15601148|ref|NP_232779. 1| [Vibrio cholerae] MSVYLNMQNKQYKLSQLAQEHLLKIKHYTIENFAEAQWQKYKSTLLSGFQTLADNPGLGK SCEDIYQNGFYFPVGKHMAY YTKEANFILIVAVLGQSQLPQKHLKQSRFVS YTKEANFILIVAVLGQSQLPQKHLKQSRFVS >gi|28898659|ref|NP 798264. 1| protein [Vibrio parahaemolyticus RIMD 2210633] MTEIIYTDTFGNTADERIDYLSQWTPTPQWEKVETLIETFE >gi|28898658|ref|NP_798263. 1| protein [Vibrio parahaemolyticus RIMD 2210633] MYPACYELISLGVYHFRQFSFDGFKIIYQYDEEANKIYALVQISDRQGLQKTLVDYCIRF L >gi|27365829|ref|NP_761357. 1| Predicted transcriptional regulator [Vibrio vulnificus CMCP6] MAKNTSITLGDHFDGFIANQIQSGRYGSASEVIRSALRLLETQETKMNTLRQLLVEGEES GVADYDLDSFINELDSEERK >gi|27365828|ref|NP_761356. 1| Plasmid stabilization element ParE [Vibrio vulnificus CMCP6] MRPFQLTNKAKSDLRDIALFTSRRWGREQRNIYLKQFDDSFWLLAENPDIGKACDEIRDG YRKFPQGSHVIFYRQIGSQN IEIIRILHKSMDVNPIFGA IEIIRILHKSMDVNPIFGA >gi|21240854|ref|NP_640436. 11 [Xanthomonas axonopodis pv. citri str. 306] MRTELVTTLKRQATELLAAAERDKEPILITQHGLPSAYLVDVASYERMQQRIALLEGIAR GEMAVAEGRTLSHEQARHRM ARWLK >gi|21240855|ref|NP_640437. 11 [Xanthomonas axonopodis pv. citri str. 306] MAEIIWSVPALADLDAIADYIAIDNAPAAAALVKRVFGHVEQLIEHPDSGSRPQELKRSR YRQIVEPPCRVFYRVDGQRI WWHVMRSERALRGNRLSR >gi|21243162|ref|NP_642744. 1| [Xanthomonas axonopodis pv. citri str. 306] MVTATSIKLDDELKGRVQHLAEARRRTPHWIMREAIEQYVEREEKREALNRDTLKAWDEF QATGLHVTAEEVDKWLASWG TDDELPPPECHK >gi|21243161|ref|NP_642743. 1| [Xanthomonas axonopodis pv. citri str. 306] MPQVIFAPAAIGDMQRLREFLKPKSPDAARRAGEAIRRGVQALGAHPRMGRLIEDLPEQY REWLIDFGDSGYVARYRHAG DTVTILAVRHQKEAGY >gi|15838625|ref|NP_299313. 1| plasmid stabilization protein [Xylella fastidiosa 9a5c] MSRLTIDMTDQQHQSLKALAALQGKTIKQYALERLFTGDADANQAWTELKTLLNTRIHEG LAGHVSTKNINEILDEELTE DGA

>gi|15838626|ref|NP_299314. 1| plasmid stabilization protein [Xylella fastidiosa 9a5c] MTGYVLTEAAESDLRGIVRYTRKQWGNAQVRHYIATLERGIASLAEGRGAFNDMSSLFPA LRMGRYEHHYVFCLPREEAP ALIVAIFHERMDLMTRLADRLK ALIVAIFHERMDLMTRLADRLK >gi|15838662|ref|NP_299350. 1| [xylella fastidiosa 9a5c] MSRNTSVALGPHFTSFIDAQVQGGRYGTASDWRAGLRLLEEHETKVKALQDALNVRHQSG EPRPFDSEVFLSRMHTQHG >gi|15838661|ref|NP_299349. 1| protein [Xylella fastidiosa 9a5c] MAKSYRLTPLAEADLEEIWFYTFRHWSIGQADSYHRSLVAVFEGLAAGTKLRPPFCSAGL Q ------------------------------------------------------------ ------------- >gi|28867472|ref|NP_790091. 1| prevent-host-death family protein [Pseudomonas syringae pv. tomato str. DC3000] MRVETISYLKRNAADLPLDEPLIVTQNGVPAYWESYADRKRRDESIALVKLLAISSREYS QGKHCSADELKARLSRRFA HKE >gi|28867473|ref|NP_790092. 1| [Pseudomonas syringae pv. tomato str. DC3000] MNMFALRFTDVAQQSLEDQVEHLAVYQGFSPAAQRIDTLIDAIQDKLLSTPLGYPVSPQL SELGVLHYRELNADGYRIFY EVRETDDINVIVIVLVLGGKQSVEQALIRYCLLQPI The following sequences were found in a later, supplementary search : >gi|15888422|ref|NP_354103. 1| AGR_C_1994p [Agrobacterium tumefaciens str. C58] MPEIHLSEQDEKFIEEQVAAGIYSDADAVIHASLQLLSSDEGKRAALKLLIQEGIDDAEA GRVHRYASQNDFLSDIKRVS AQQKTGTDH >parE|15887359 : cl070511-1070861, length 117, A. tumefaciens_str_C58_Cereon_circ_chr, parE parE MSNAFPPSKKRGPIIKIRSITTRARRDLAEDHAYIETENPVAADRLVLDIYNKIESIA AIGLTGVSRHGYGTGLRSIAYRDRVIFFRVNNGELTVMRVLHGHQDISADDFKQEEN >parD|17933925 : c830914-831318, length 135, A. tumefaciens_str_C58_U_Wash_circ_chr, parD MIWCSADVKPVYLPQGPRLQGFAFDLSLPMTDLMHRNCNAGRRSMKTATIPSLRVTADFR EAAESVLKDGETLSAFMEEAVRKQVEIRKSQAEFIKQGLAAREESKRTGVYHKAEDVLAE LKAMLDEKLAEDNDK >parD|17933925 : c830914-831318, length 135, A. tumefaciens_str_C58_U_Wash_circ_chr, parD MIWCSADVKPVYLPQGPRLQGFAFDLSLPMTDLMHRNCNAGRRSMKTATIPSLRVTADFR EAAESVLKDGETLSAFMEEAVRKQVEIRKSQAEFIKQGLAAREESKRTGVYHKAEDVLAE LKAMLDEKLAEDNDK LKAMLDEKLAEDNDK >parD|17933925 : 1304610-1304918, length 103, A. tumefaciens_str_C58_U Wash circ_chr, parD MVEAPMPTRNVVLTQHHEEIIDDLVKSGRYQNASEVLREGLRLIERRERLEATRLETLKV AAQQGFCDLDQGRYIDVSDDALDDFISAFGREAEVRLTKSDDK >parE|17933925 : 1304918-1305289, length 124, A. tumefaciens_str_C58_U_Wash_circ_chr, parE MTTYRLSDAAQSDIIEILGWTHATFGAAARKRYEKLLATALRDVAVDPLRAGTNIRAELG EDVRSYHLRYSRERAKSETGLVKNPRHLLLYRALRPGLVGVGRVLHDSMEIERHLPDDYG DITF DITF >gi] 16125306refNP419870. 1 hypothetical protein CC1054 [Caulobacter crescentus CB15] MFWIFVMAKPASLSIELDSDLDRRLSEIAEGMDQPKTAIIERALRDFVELRDWQDAAIDE GLRAAEEGRVFDHDKVGEWI DSWGTPNERPMPSRD >parE|16124256 : 1186395-1186610, length 72, Caulobacter_crescentus, parE MRVTWTDSASRDLRFAYAWIAQDRPTAALKQVRRIWEFAAKLSDFPNLGRPGRRPGTRNW SCRAAPSLSLTE >gi|15800838|ref|NP_286854. 1| unknown protein encoded by cryptic prophage CP-933M [Escherichia coli 0157 : H7 EDL933] MGTALSPIVSEFETTEQENSYNEWLRTKVTSSLADTRPAIPHDEVMAEMENLIAQIAVTN KSE >parE|16445223 : cl256683-1256967, length 95, E. coli 0157 H7 EDL933, parE MLPILWLPSARDDLRQIITYIAKENPPAARRLKIRIETSVLPLSEHPYLYPPSERVSGLR EIVTHPNYIILYRVAASSIEIVSVTHSRRQFPFSI EIVTHPNYIILYRVAASSIEIVSVTHSRRQFPFSI

>gi|15801987|reftNP_288008. 1| unknown protein encoded by cryptic prophage CP-933P [Escherichia coli 0157 : H7 EDL933] MNRALSPMVSEFETIEQENSYNEWLRAKVATSLADPRPAIPHDEVERRMAERFAKMRKER SKQ >parE|16445223 : cl256683-1256967, length 95, E.-coli-0157-H7-EDL933, pare MLPILWLPSARDDLRQIITYIAKENPPAARRLKIRIETSVLPLSEHPYLYPPSERVSGLR EIVTHPNYIILYRVAASSIEIVSVTHSRRQFPFSI EIVTHPNYIILYRVAASSIEIVSVTHSRRQFPFSI >parD|13470324 : 1972578-1972823, length 82, Mesorhizobium loti, parD MMAMTAFTVRLSDDTTDRLDQLAEKLDRSRSYVAAQAIEDFVTRQEWQLAEIEAGLAEAE RGEFANEQELAAVIAKYIKPAG >parE|13470324 : 1972805-1973119, length 113, Mesorhizobium_loti, parE MYQARRLIVSHKTIRWTKRALRRLDEIGAHIEKDSPEAASRVIARILSAAELLTQQPAMG RVGRIKATRELVLVDIPYIVPYRVSGNTVEILTVIHAAQQWPRTL ------------------------------------------------------------ ------- >parD|15607142 : c2402508-2402720, length 71, M. tuberculosisH37Rv, ParD MVVNRALLASVDALSRDEQIELVEHINGNLAEGMHISEANQALIEARANDTDDAHWSTID DFDKRIRARLG >gi|15609279|ref|NP_216658. 11 hypothetical protein Rv2142c [Mycobacterium tuberculo- sis H37Rv] MTRRLRVHNGVEDDLFEAFSYYADAAPDQIDRLYNLFVDAVTKRIPQAPNAFAPLFKHYR HIYLRPFRYYVAYRTTDEAI DILAVRHGMENPNAVEAEISGRTFE DILAVRHGMENPNAVEAEISGRTFE >parD|30248031 : 1479335-1479618, length 88, Nitrosomonas_europaea, parD MKSSTIPSLRVTPEFRRDAESVLREGESLSAFVEESLRQHIERRRTQQEFIARGLTAREA AKSSGQYASKAEVMSSLHSILDEQRSKE >gi|30249332|ref|NP_841402. 1| Hypothetical protein NE1353 [Nitrosomonas europaea ATCC 19718] MSFHVRFTLEAKADIERLYRFLAEHDFDVAERTLETIDSAWSLLEQFPFSCRKIDDANPF LREFIISFGNSGYVVLFEIE DSNTVTVLAVRHQLEDDYY DSNTVTVLAVRHQLEDDYY >parD16763390 : c3102440-3102715, length 91, Salmonella-typhimurium-LT2, ParD MTVDLGDELREFIESLIESGDYRTQSEVIRESLRLLREKQAESRLQALRELLAEGLNSGE PQAWEKDAFLRKVKTGMIKPDENGKINAKGQ >parE|16763390 : c3102178-3102468, length 96, Salmonella_typhimurium LT2, ParE MRMVKLTPKASEDLENIWHYGWQHFGEIQADRYINHLSEIFSIMSANNIGTPRPELGEYI YALPFKRHIIYFIQSVTEVIVIRILSQNQDAGKHVNWL YALPFKRHTIYFTQSVTEVTVTRII, SQNQDAGKHVNWL >parD|16758993 : c2958334-2958059, length 91, corrected start, Salmonella_typhi, ParD MTVDLGDELREFIESLIESGDYRTQSEVIRESLRLLREKQAESRLQALRELLAEGLNSGE PQAWEKDAFLRKVKTGMIKPDENGKINAKGQ >parEi16758993 : c2957794-2958012, length 73, Salmonella_typhi, ParE MRTVKLTPKASEDLENIWHYGWQHFGEIQADRYIHHLSEIFSIMSANNIGTPRPELGEYI YALPFERHIIYFI >parD|29140543 : c2944229-2943954, length 91, corrected start, Salmonella_typhi_Ty2, ParD MTVDLGDELREFIESLIESGDYRTQSEVIRESLRLLREKQAESRLQALRELLAEGLNSGE PQAWEKDAFL RKVKTGMIKPDENGKINAKGQ >parE|29140543 : c2943689-2943907, length 73, Salmonella_typhi_Ty2, ParE MRTVKLTPKASEDLENIWHYGWQHFGEIQADRYIHHLSEIFSIMSANNIGTPRPELGEYI YALPFERHIIYFI YALPFERHIIYFI >parD|21240774 : c3665126-3665371, length 82, Xaxonopodispvcitristr306, parD MSPGRRKMPELRRTALSSTPLRKKSRRTSAALHSMPKRSNAGLLSKAATTRCPGRTYAST CSSLLTERTPRHRSPAPSSADR >gi|21232522|ref|NP_638439. 11 Hypothetical protein XCC3091 [Xanthomonas campestris pv. campestris str. ATCC 33913] MTRIALAARVADDARRLVAYLLEHDAASVQRKLAGIFQAIDALADNPLMGRAVHGGFREL VIGRDASGYLALYRYAPLDD

TVYVLAIRSQREAGYLESLF TVYVLAIRSQREAGYLESLF >gi) 28198860) ref) NP779174. 1) plasmid stabilization protein [Xylella fastidiosa Teme- culal] MSCLTIDITDQQHQSLKALAALQGKTVEQYALERLFPSDTDADQAWQDLKTLVGTRISEG LAGKVSTKSINEILNEELT >gi|28198859|ref|NP_779173. 11 plasmid stabilization protein [Xylella fastidiosa Teme- culal] MTGYILTAAAETDLRSIIRYTRKQWGDAQMRRYIATLEQDMASLAAGRGVFRNMSVLFPA LRMGRCEHHYVFCLPREGAP ALIVAIFHERMDLMTRLADRLK Homoloques of mazEF (Chp) toxin-antitoxin system polypeptides >giI15607142 : 3110734-3110507, length 76, MazE MKLSVSLSDDDVAILDAYVKRAGLPSRSAGLQHAIRVLRYPTLEDDYANAWQEWSAAGDT DAWEQTVGDGVGDAPR >gi|15609938|ref|NP_217317. 11 Rv2801c [Mycobacterium tuberculosis H37Rv] MMRRGEIWQVDLDPARGSEANNQRPAWVSNDRANATATRLGRGVITWPVTSNIAKVYPFQ VLLSATTTGLQVDCKAQA EQIRSIATERLLRPIGRVSAAELAQLDEALKLHLDLWS >gi|15607142 : 2234919-2234644, length 92, MazE MEVIPGYTICMKTAISLPDETFDRVSRRASELGMSRSEFFTKAAQRYLHELDAQLLTGQI DRALESIHGTDEAEALAVANAYRVLETMDDEW >gi|15609128|ref|NP_216507. 1| Rvl991c [Mycobacterium tuberculosis H37Rv] MVISRAEIYWADLGPPSGSQPAKRRPVLVIQSDPYNASRLATVIAAVITSNTALAAMPGN VFLPATTTRLPRDSWNVTA IVTLNKTDLTDRVGEVPASLMHEVDRGLRRVLDL IVTLNKTDLTDRVGEVPASLMHEVDRGLRRVLDL >gi|15607142 : 2547085-2546840, length 82, MazE MAEPETLPGRWLPECACLAETVSWEQSRLWSRLLCRPHFRHALPGLTGGSASRPSARSAR LVRQPRMTLFSLDHRDGVDARC >gi|15609411|ref|NP_216790. 11 Rv2274c [Mycobacterium tuberculosis H37Rv] MSIARSAQPIGWISCPPKGGSSCCRCGGGYTHIFCVSAWTGLWDLQAEQVRSWTERLRRR IGRGAPILAGTLAPGVGL AAQNREFRQFTGRSAPPSATIAFGE AAQNREFRQFTGRSAPPSATIAFGE >gi|15839372 : 3105455-3105228, length 76, MazE MKLSVSLSDDDVAILDAYVKRAGLPSRSAGLQHAIRVLRYPTLEDDYANAWQEWSAAGDT DAWEQTVGDGVGDAPR >gi|15842339|ref|NP_337376. 11 pemK protein [Mycobacterium tuberculosis CDC1551] MRRGEIWQVDLDPARGSEANNQRPAVVVSNDRANATATRLGRGVITVVPVTSNIAKVYPF QVLLSATTTGLQVDCKAQAE QIRSIATERLLRPIGRVSAAELAQLDEALKLHLDLWS QIRSIATERLLRPIGRVSAAELAQLDEALKLHLDLNS >gi|21672841 : 947841-948164, length 108, MazE MLLEGSIGLLPDALLNNEEPEQNTGYNSSARCIVNREDQAGITRKETIGASVWFGLVCVT DESVAYRYDGLAARSLRLWTTPSLKKQQIAKAGTHEKGIGGHDCLAGQ >gi|21673827|ref|NP_661892. 11 conserved [Chlorobium tepidum TLS] MKRGSWTIALQGNDGKLRPAWVLSDYFPEHPSVTVLPIISDLRSTPFFRIDVEPEAQNGL LKPSRIMIDKAQAVPSEK IGKVIGLLDDTKMMAVNRALALWFGFA IGKVTGLLDDTKMMAVNRALALWFGFA >gi|17988344 : 197880-198089, length 70, MazE MEAETIPREGRRTSRSFARLRFALDPDLGAGRAFSSFRDEAHRQSLTVASRSHAADDLAF INSVSDWSDE >gi|17988530|ref|NP_541163. 1| PEMK-LIKE PROTEIN 1 [Brucella melitensis] MKRGEIWTVGGGKDRAGKPRPAVIVQDDRFDATGSITICAFTTNETNVPLFRLAVEPNER NGLRSVCRLMVDKITTAPKS MMAVQVGRNPPGHS MMAVQVGRNPPGHS >gi|23499767 : 1101529-1101320, length 70, MazE MEAETIPREGRRTSRSFARLRFALDPDLGAGRAFSSFRDEAHRQSLTVASRSHAADDLAF INSVSDWSDE >gi|23500829|ref|NP_700269. 1| pemK family protein [Brucella suis 1330]

MKRGEIWTVGGGKDRAGKPRPAVIVQDDRFDATGSITICAFTTNETNVPLFRLAVEPNER NGLRSVCRLMVDKITTAPKS MMAVQVGRNPPGHS MMAVQVGRNPPGHS >gi|30248031 : 1002936-1002703, length 78, MazE MKMTIIAKVTSKGQTTIPADIRAALRIKPGDLIIWEMSDDGSARIRRVQPLDIEYLKAVE GTLSEWAGAADEEAYREL >gi|30248925|ref|NP_840995. 1| conserved [Nitrosomonas europaea ATCC 19718] MSYERFTVLKVPFPFTDRTAAKNRPALVLSDAATFNDPIGHSVLAMITSAANPAWPLDCL IDDLVSAGLPAPSWRFKLF TLDHRLIRGELGRLAVSDSIQVTRSLYQLFGMAAVR >gi15607800refINP_215174. 1 protein Rv0660c [Mycobacterium tuberculosis H37Rv] MLSFRADDHDVDLADAWARRLHIGRSELLRDALRRHLAALAADQDVQAYTERPLTDDENA LAEIADWGPAEDWADWADAA R >gi|15607799|ref|NP_215173. 1| protein Rv0659c [Mycobacterium tuberculosis H37Rv] MRRGELWFAATPGGDRPVLVLTRDPVADRIGAVWVALTRTRRGLVSELELTAVENRVPSD CWNFDNIHTLPRTAFRRR ITRLSPARLHEACQTLRASTGC >gi|15609080|ref|NP_216459. 1| protein Rv1943c [Mycobacterium tuberculosis H37Rv] MKTARLQVTLRCAVDLINSSSDQCFARIEHVASDQADPRPGVWHSSGMNRIRLSTTVDAA LLTSARDMRAGITDAALIDE ALAALLARHRSAEVDASYAAYDKHPVDEPDEWGDLASWRRAAGDS >gi|15609079|ref|NP_216458. 1| protein Rv1942c [Mycobacterium tuberculosis H37Rv] MTALPARGEVNMCEMAEIGRRPVVVLSRDAAIPRLRRALVAPCTTTIRGLASEVVLEPGS DPIPRRSAVNLDSVESVSVA VLVNRLGRLADIRMRAICTALEVAVDCSR VLVNRLGRLADIRMRAICTALEVAVDCSR >gi|15608243|ref|NP_215619. 1| proteìn Rv1103c [Mycobacterium tuberculosis H37Rv] MYLPWGWLAGGANGFGAGAYQTGTICEVSTQIAVRLPDEIVAFIDDEVRGQHARSRAAVV LRALERERRRRLAERDAEI LATNTSATGDLDTLAGHCARTALDID >gi|15608242|ref|NP_215618. 1| protein Rv1102c [Mycobacterium tuberculosis H37Rv] MRPIHIAQLDKARPVLILTREVVRPHLTNVTVAPITTTVRGLATEVPVDAVNGLNQPSWS CDNTQTIPVCDLGRQIGYL LASQEPALAEAIGNAFDLDWWA LASQEPALAEAIGNAFDLDNWA >gi15608632IrefINP_216010. 1 protein Rv1494 [Mycobacterium tuberculosis H37Rv] MPFLVALSGIISGVRDHSMTVRLDQQTRQRLQDIVKGGYRSANAAIVDAINKRWEALHDE QLDAAYAAAIHDNPAYPYES EAERSAARARRNARQQRSAQ >gi) 15608633jref) NP216011. 1] protein Rv1495 [Mycobacterium tuberculosis H37Rv] MNAPLRGQVYRCDLGYGAKPWLIVSNNARNRHTADWAVRLTTTRRTIPTWVAMGPSDPLT GYVNADNIETLGKDELGDY LGEVTPATMNKINTALATALGLPWP LGEVTPATMNKINTALATALGLPWP >gijl5841473ref] NP336510. l) DNA-binding protein, CopG family [Mycobacterium tuber- culosis CDC1551] MKTAISLPDETFDRVSRRASELGMSRSEFFTKAAQRYLHELDAQLLTGQIDRALESIHGT DEAEALAVANAYRVLETMDD EW >gi|15841472|ref|NP_336509. 11 [Mycobacterium tuberculosis CDC1551] MVISRAEIYWADLGPPSGSQPAKRRPVLVIQSDPYNASRLATVIAAVITSNTALAAMPGN VFLPATTTRLPRDSWNVTA IVTLNKTDLTDRVGEVPASLMHEVDRGLRRVLDL IVTLNKTDLTDRVGEVPASLMHEVDRGLRRVLDL >gi|15840063|ref|NP_335100. 1| protein [Mycobacterium tuberculosis CDC1551] MTMLSFRADDHDVDLADAWARRLHIGRSELLRDALRRHLAALAADQDVQAYTERPLTDDE NALAEIADWGPAEDWADWAD AAR >gi|15840062|ref|NP_335099. 1| protein [Mycobacterium tuberculosis CDC1551] MRRGELWFAATPGGDRPVLVLTRDPVADRIGAVWVALTRTRRGLVSELELTAVENRVPSD CWNFDNIHTLPRTAFRRR ITRLSPARLHEACQTLRASTGC ------------------------------------------------------------ ------------- >gi|15841414|ref|NP_336451. 1| protein [Mycobacterium tuberculosis CDC1551] MKTARLQVTLRCAVDLINSSSDQCFARIEHVASDQADPRPGVWHSSGMNRIRLSTTVDAA LLTSARDMRAGITDAALIDE ALAALLARHRSAEVDASYAAYDKHPVDEPDEWGDLASWRRAAGDS >gi|15841413|ref|NP_336450. 11 protein [Mycobacterium tuberculosis CDC1551] MAAGGWRLVTALPARGEVWWCEMAEIGRRPWVLSRDAAIPRLRRALVAPCTTTIRGLASE WLEPGSDPIPRRSAVNLD SVESVSVAVLVNRLGRLADIRMRAICTALEVAVDCSR

------------------------------------------------------------ ------------- >gi|15840542|ref|NP_335579. 11 protein [Mycobacterium tuberculosis CDC1551] MSTQIAVRLPDEIVAFIDDEVRGQHARSRAAWLRALERERRRRLAERDAEILATNTSATG DLDTLAGHCARTALDID >gi|15840541|ref|NP_335578. 1| protein [Mycobacterium tuberculosis CDC1551] MRPIHIAQLDKARPVLILTREWRPHLTNVTVAPITTTVRGLATEVPVDAVNGLNQPSWSC DNTQTIPVCDLGRQIGYL LASQEPALAEAIGNAFDLDWWA >gi|15840957tref|NP_335994. 1| protein [Mycobacterium tuberculosis CDC1551] MPFLVALSGIISGVHDHSMTVRLDQQTRQRLQDIVKGGYRSANAAIVDAINKRWEALHDE QLDAAYAAAIHDNPAYPYES EAERSAARARRNARQQRSAQ >gi|15840958|ref|NP_335995. 1| protein [Mycobacterium tuberculosis CDC1551] MNAPLRGQVYRCDLGYGAKPWLIVSNNARNRHTADWAVRLTTTRRTIPTWVAMGPSDPLT GYVNADNIETLGKDELGDY LGEVTPATMNKINTALATALGLPWP IGEVTPATMNKII3TALATALGLPWP >gi|17230704|ref|NP_487252. 1| cell growth regulatory protein [Nostoc sp. PCC 7120] MTTWAKWGNSLAVRIPRSIAEQAHVTEGTDINFSVEGNSIVITPKRRKKYTLDELLEGMT PDNFHPEFETGDAVGNEAW >gi|17230703|ref|NP_487251. 1| cell growth regulatory protein [Nostoc sp. PCC 7120] MKPPYFPNRGDIVKLEFGSAQQFTAESIQRVFTLRNSGMSFDDIAITLNNELQQQGREQT GYRPVLVISPIKYNQMASLV LACPITTNAKGLRFEVPLIEGMKTKGWLADQIKTLDWKARKVKFVESVTEDLIEEVQAKL ETLIL ------------------------------------------------------------ ------------- >gi|17232412|ref|NP_488960. 1| unknown protein [Nostoc sp. PCC 7120] MLSPHLQAIERDIRTLSLAELEWLLERITKQVQTRKQTSDKFTDMQYMNEQLAAMANDLE VQTEISLINHEFNSTEMDGL >gi|17232413|ref|NP_488961. 11 protein [Nostoc sp. PCC 7120] MSIERGQIYFVNLNPVHGREQAGARPVLVLSTDAINQLPLVITVVVGTKGTNIKRDYPTN IRVSPSDSGLVIETVFLCFQ IRSLDPNRFPTDPSGKLSASKMLEVETAVRYCIIGL IRSLDPNRFPTDPSGKLSASKMLEVETAVRYCLGL >gi|17227834|ref|NP_484382. 11 unknown protein [Nostoc sp. PCC 7120] MDALIQELDTKMRQWQPEIVKQVRQSLAEIIELADQDALDILRSRIVEQEVLDLIDEPET R >gi|17227833|ref|NP_484381. 11 protein [Nostoc sp. PCC 7120] MNPKPGEVWLVDLGLAAKARPWIVSRYDLTPPRALVIYIPITTQNRGSAYEVELPVLSFL RQGSVANVQGLGSIPSVRL ERKLGELSKETMLEIKQALMFTLDLWDTQDDGAFNTDEIG >gi|17228252|ref|NP_484800. 11 unknown protein [Nostoc sp. PCC 7120] MQTDNIPQQRLIGKIRQLVPEQWLVERFIDSLSQKNEEYNLTLAATKLSEPVLQRIWDNP DDAEYDKL >gi|17228253|ref|NP_484801. 1| protein [Nostoc sp. PCC 7120] MTNYKFGDVILVPFPFTDQTTTKKRPSWVSSTDYQRQRSDLILIAVTSTTNPVTSFAEMT ITEWKAAGLLKPSIIKPVL TTIDKMLVIKKLGELQEVDTQALHNLLQIILGG TTIDKMLVIKKLGELQEVDTQALHNLLQIILGG >gi|16330121|ref|NP_440849. 1| unknown protein [Synechocystis sp. PCC 6803] MSINAYKLATTLTEDGTLLLQDLPCPAGTSVEVIVLVAPQGMVLPQAERAQGPAPGKVGE AGADYMAATADTMTEWNSEA DNSAYRHL >gi|16330120|ref|NP_440848. 1| unknown protein [Synechocystis sp. PCC 6803] MNTIYEQFDWVIVPVPFTDRQSDIRRPALILSDAPAFNNRIGHSVMAMITSAKNAPWPLD TPIEDTRSAGLFTPSWRMK LFTLEHKYIDDCVGSLSKQDRLMVKSAFPHVFKLG >gi|30260429|ref|NP_842806. 1| [Bacillus anthracis str. Ames] MSESSVTTEIWRLPKQMVTELDGIGKQENKNRHELICQATQLLLRQHKTKKRYQHESMRR GYIEMGKINLGIASEAFLA EYEAAHTVERLVSGG >gi|30260430|ref|NP_842807. 1| transcriptional regulator, PemK family [Bacillus an- thracis str. Ames] MIVKRGDVYFADLSPWGSEQGGVRPVLVIQNDIGNRFSPTVIVAAITAQIQKAKLPTHVE IDAKKYGFERDSVILLEQI RTIDKQRLTDKITHLDEVMMIRVDEALQISLGLIDF RTIDKQRLTDKITHLCEVMMIRVDEALQISLGIjIDF gi|30018502|ref|NP_830133. 1| Cytosolic Protein [Bacillus cereus ATCC 14579] MSESSVTTEIWRLPKQMVTELDGIGKQENKNRHELICQATQLLLRQHKTKKRYQHESMRR GYIEMGKINLGIASEAFLA EYEAAHTVERLVSGG

>gi) 30018503) ref) NP830134. l) pEMK-like protein [Bacillus cereus ATCC 14579] MIVKRGDVYFADLSPVVGSEQGGVRPVLVIQNDIGNRFSPTVIVAAITAQIQKAKLPTHV EIDAKKYGFERDSVILLEQI RTIDKQRLTDKITHLDEVMMIRVDEALQISLGLIDF ------------------------------------------------------------ ------------- >gi|15616282|ref|NP_244587. 1| suppressor of ppGpp-regulated growth inhibitor (ChpA/MazF) [Bacillus halodurans] MTLMTTIQKWGNSLAVRIPNHYAKHINVTQGSEIELSLGSDQTIILKPKKRKPTLEELVA KITPENRHNEIDFGRTGKEL L >gi|15616283|ref|NP_244588. 1| ppGpp-regulated growth inhibitor (ChpA/MazF) [Bacillus halodurans] MPVPDRGNLVYVDFNPQSGHDQAGTRPAIVLSPKLFNKNTGFAWCPITRQQKGYPFEIEI PPGLPIEGVILTDQVKSLD WRARNFHIKGQAPEETVTDCLQLIHTFLS MRARNFHIKGQAPEETVTDCLQLIHTFLS >gi|15613084|ref|NP_241387. 1| BH0521~unknown conserved protein in B. subtilis [Bacil- lus halodurans] MSFVSESSTKRIWNLPQHLLNEVDGVIKQEKVNRSEFFSQATKMYLRERKKRQIREKMQQ GYLEMAKINLNIASEAFLA EEEAEHTLDRLVSGV >gi|15613085|ref|NP_241388. 11 BH0522-unknown conserved protein [Bacillus halodurans] MIVKRGDVYFADLSPWGSEQGGVRPVLVIQNDIGNRFSPTVIVAAITAQIQKAKLPTHVE INAKRYGFDRDSVILLEQI RTIDKQRLTDKITHLDDDMMSKVNDALLISLGLIDF >gi16077532 ref NP388346. lj ydcD [Bacillus subtilis] MSESSARTEMKISLPENLVAELDGVAMREKRSRNELISQAVRAYVSERTTRHNRDLMRRG YMEMAKINLNISSEAHFAEC EAETTVERLVSGG >gi|16077533|ref|NP_388347. 1| similar to proteins [Bacillus subtilis] MIVKRGDVYFADLSPWGSEQGGVRPVLVIQNDIGNRFSPTAIVAAITAQIQKAKLPTHVE IDAKRYGFERDSVILLEQI RTIDKQRLTDKITHLDDEMMDKVDEALQISLALIDF RTIDKQRLTDKITHLDDEMMDKVDEALQISLALIDF >gi|15893784|ref|NP_347133. 1| Uncharcterized small conserved protein, YhhG family [Clostridium acetobutylicum] MSSSKRLWNLSETLYDEFNKALKEDCKKRSEFIREAIILYIEERKKLQQIELVKKGYSEM AKLNIEICECGFSSDLEDL NQYEVMLSESDLLDDNSGKTRRYILC >gi|15893785|ref|NP 347134. 1| PemK family of DNA-binding proteins [Clostridium aceto- butylicum] MTIWKRGDIFYADLSPWGSEQGGIRPVIIIQNDMGNKYSPTVIVAAITSQINKAKLPTHV EISSEDYGLNKDSWLLE QIRTLDKRRLKEKIGHMTDMDMKKVDEALLISIGLQNMFESV >gi|18309276|ref|NP_561210. 11 protein [Clostridium perfringens] MSVSKINKQDSKKEKKIENFSQLKGRNIITYSEDKKEDDFYEAMKEGYKAMALINSQYAE EGTSVEYFDQIEYETWLCGV >gi18309277refNP_561211. 1I [Clostridium perfringens] MASLNVKRGDIFYADLSPWGSEQGGIRPVIIIQNDIGNRYSPTVIVAAITSQINKAKLPT HVEISSEEYGLNRDSWLL EQIRTLDKKRLKEKIGHMTEDDMKKVNKSLLISLNLQ >gi|29375413|ref|NP_814567. 1| uridine kinase [Enterococcus faecalis V583] MKDSQPIIIGVTGGSGSGKTSVSRAIFNNFPDHSIMMLEQDSYYKDQSHLSFEERLNTNY DHPFAFDTDLLIQHVEQLLN YQAIEKPVYDYVAHTRSTETVIQEPKEVIILEGILILEDRRLRDLMDIKVYVDTDDDIRI IRRIKRDMEERGRTLDSVIE QYLTWKPMYHQFIEPTKRYADIIVPEGGENHVAIDLINTKVDSILTKM >gi|29375414|ref|NP_814568. 1| transcriptional regulator, PemK family [Enterococcus faecalis V583] MIKRGEVFYANLSPWGSEQGGIRPVLIIQNNKGNLFSPTLIVAPITRNVSKRLQPTQVLI EIPHNECRTPSLILLEQIR TLDKERMLHKVCQLSREEMEQVNQALKVSVGIR TLDKERMLHKVCQLSREEMEQVNQALKVSVGIR >gi|29377704|ref|NP_816858. 1| transcriptional regulator, AbrB family [Enterococcus faecalis V583] MTSTKTRKQGNSLVITIPATLGVKEGEEFVILRKNNGSIALIPKVEDFFENTAEGEFYLP ELAIDYSPSGGEVDGL >gi|29377705|ref|NP_816859. 1| transcriptional regulator, PemK family [Enterococcus faecalis V583] MGYKPTQRDIVIIDFAPSKGYEIRKRRPALVMSKDSYNISTNLVIVCPITSLDKERPFLV PIYSEKLHTSDNAVSKVNTL QVYSLDYTEQAQRRIKYVDTLDEETFYEIAQKFLQNFSFAV

------------------------------------------------------------ ------------- >gif28379347refNP_786239. 11 unknown [Lactobacillus plantarum WCFS1] MCLLIRGGLDMIEVKTVSRGNSLALSLPKDGRFKKGQRWLLIPSSDGESYTLVPRIENPY AGSKPKRPMTEAWSDVDWNE VE >gi|28379346|ref|NP_786238. 1| cell growth regulatory protein [Lactobacillus plantarum WCFS1] WCFS1] ATPRAGRSITYIETMRSADFYHVAQTVYYNFDFPF ATPRAGRSITYIETMRSADFYHVAQTVYYNFDFPF >gi|16799959|ref|NP_470227. 11 similar to B. subtilis YdcD protein [Listeria innocua] MLEKEKRMIISVELTQEMVQELDWWEKEKMGRSEVIMEATQQFLQEKRARELRDEMERGY AEMATINFAIACECTHVEA EAEDRNISILGG >gi|16799960|ref|NP_470228. 1| similar to B. subtilis YdcE protein [Listeria innocua] MMVKRGDVYYADLSPWGSEQGGIRPVLIIQNDIGNRFSPTVIVAAITAKIQKAKLPTHVE ATRKDGFERDSVILLEQIR TIDKQRLTDKITHLDEELMAKVNQALEVSLGWEF TIDKQRLTDKITHLDEELMAKVNQALEVSLGWEF >gi|16802928|ref|NP_464413. 1| similar to B. subtilis YdcD protein [Listeria monocyto- genes EGD-e] MLEKENRMIISVELTQEMIQELDVWEKEKMGRSEVIMEATQQFLQEKRARELRDEMERGY AEMATINFAIACECTHVEA EAEDRNISILGG >gi|16802929|ref|NP_464414. 11 similar to B. subtilis YdcE protein [Listeria monocyto- genes EGD-e] MMVKRGDVYYADLSPWGSEQGGIRPVLIIQNDIGNRFSPTVIVAAITAKIQKAKLPTHVE ATRKDGFEKDSVILLEQIR TIDKQRLTDKITHLDEDLMAKVNKALEVSLGWEF >gi|23098077|ref|NP_691543. 1| protein [Oceanobacillus iheyensis HTE831] MSESLQEIMVKMPKNLLSEVDGLMKYENSDLSDFICEATQIYLNHKKEEHIQRFHETMQR GYEEMGRINLTIASEAFQAE EEAENTLERSVIGV >gi|23098078|ref|NP_691544. 1| protein [Oceanobacillus iheyensis HTE831] MIVQRGEVYFADLSPWGSEQGGVRPVLILQNDIGNRFSPTVIVAAITAQIQKAKLPTHVE IDAKRYGFDRNSVILLEQI RTLDKQRLTDKITKLDKEMMIKINQALEISLGLKDVYGG RTLDKQRLTDKITKLDKEMMIKTNQALEISLGLKDVYGG >gi|20808551|ref|NP_623722. 1| predicted Transcriptional regulator containing the CopG/Arc/MetJ DNA-binding domain and a metal-binding domain [Thermoanaerobacter teng- congensis] MGETKRILVSLPQSLLEEVDVLAAMENRNRSEFIREAMKLYIRERKKAQIRESMKKGYME MAAINSELAEMGLTAENECF AGYEMKLKKCD >gi|20808550lref|NP_623721. 11 Growth inhibitor [Thermoanaerobacter tengcongensis] MIMVVKRGDLFYADLSPVIGSEQGGIRPVLIIQNDIGNKYSPTVIVAAITSQINKAKLPT HVEINGAEYGLQKDSVILLE QIRTIDKKRLREKIGHLDQEMMEKVNEALQISLGLIDF >gi|21283722|ref|NP_646810. 1| protein [Staphylococcus aureus subsp. aureus MW2] MLSFSQNRSHSLEQSLKEGYSQMADLNLSLANEAFPIECEACDCNETYLSSNSTNE >gi|21283721|ref|NP_646809. 1| [Staphylococcus aureus subsp. aureus MW2] MIRRGDVYLADLSPVQGSEQGGVRPWIIQNDTGNKYSPTVIVAAITGRINKAKIPTHVEI EKKKYKLDKDSVILLEQIR TLDKKRLKEKLTYLSDDKMKEVDNALMISLGLNAVAHQKN >gi|15927644|ref|NP_375177. 1| protein [Staphylococcus aureus subsp. aureus N315] MLSFSQNRSHSLEQSLKEGYSQMADLNLSLANEAFPIECEACDCNETYLSSNSTNE >gi|15927643|ref|NP_375176. 1| [Staphylococcus aureus subsp. aureus N315] MIRRGDVYLADLSPVQGSEQGGVRPWIIQNDTGNKYSPTVIVAAITGRINKAKIPTHVEI EKKKYKLDKDSVILLEQIR TLDKKRLKEKLTYLSDDKMKEVDNALMISLGLNAVAHQKN >gi|15925059|ref|NP_372593. 1| protein [Staphylococcus aureus subsp. aureus Mu50] MLSFSQNRSHSLEQSLKEGYSQMADLNLSLANEAFPIECEACDCNETYLSSNSTNE >gi|15925058|ref|NP_372592. 1| [Staphylococcus aureus subsp. aureus Mu50] MIRRGDVYLADLSPVQGSEQGGVRPWIIQNDTGNKYSPTVIVAAITGRINKAKIPTHVEI EKKKYKLDKDSVILLEQIR TLDKKRLKEKLTYLSDDKMKEVDNALMISLGLNAVAHQKN

------------------------------------------------------------ ------------- >gi|27468591|ref|NP_765228. 11 (Staphylococcus epidermidis ATCC 12228] MLSFNQNRNHSLEQSLKEGYAQMADLNLSLATEAFPIECEACDCNESHLISNSKNE >gi|27468590|ref|NP_765227. 11 [Staphylococcus epidermidis ATCC 12228] MIRRGDVYLADLSPVQGSEQGGVRPWIIQNDTGNKYSPTVIVAAITGRINKAKIPTHVEI EKKKYKLDKDSVILLEQIR TLDKKRLKEKLTFLSESKMIEVDNALDISLGLNNFDHHKS >gi|24378686|ref|NP_720641. 1| cell growth regulatory protein [Streptococcus mutans UA159] MQLVINKWGNSSAIRLPKQLVQELQLQTNDVLDYKVSGNKIILEKVNNIPELTVEDLFKD YQGEPVNVTPALFESVGNEQ W >gi|24378687|ref|NP_720642. 11 ppGpp-regulated growth inhibitor [Streptococcus mutans UA159] MVTIKQGSIIKINLDPKQGHEQKGYRPYICLNHSIVTKYSNIGIFAPISNTKRDYPFYVS LEGTESTGKVLLDQLVTIDF NARDYRYVEDIQEDLLDELLARVKVLFEKG NARDYRYVEDIQEDLLDELLARVKVLFEKG >gi|15888279|ref|NP_353960. 1| AGR_C_1711p [Agrobacterium tumefaciens] MKMCYICCTMQERRRMTVTTKIRRQGGAAVMTIPPALLKMLGLEIGEQLTLEVDNGALVA SPVRLEKKRFTLAELLDGAE EVAALNARERAWDTAPPVGKEAL >gi|15888280|ref|NP 353961. 1| AGR_C_1712p [Agrobacterium tumefaciens] MMVRNQIPKRGDVYLVDLNPWGSEIKDEHRCWITPREINAVGLCLWPVTTGGMFTRKAGL AVNISGHKTTGVALCNQ VRSMDIVARVAQKKAKYIETLDDATIDEIAGRVISMIDPA VRSMDIVARVAQKKAKYIETLDDATIDEIAGRVISMIDPA >gi|17934847|ref|NP_531637. 1| PemI protein [Agrobacterium tumefaciens str. C58 (U. Washington)] MTVTTKIRRQGGAAVMTIPPALLKMLGLEIGEQLTLEVDNGALVASPVRLEKKRFTLAEL LDGAEEVAALNARERAWDTA PPVGKEAL >gi|17934848|ref|NP_531638. 11 PemK protein [Agrobacterium tumefaciens str. C58 (U. Washington)] MVRNQIPKRGDVYLVDLNPWGSEIKDEHRCWITPREINAVGLCLWPVTTGGMFTRKAGLA VNISGHKTTGVALCNQV RSMDIVARVAQKKAKYIETLDDATIDEIAGRVISMIDPA RSMDIVARVAQKKAKYIETLDDATIDEIAGRVISMIDPA >gi|15891930|ref|NP_359644. 1| unknown [Rickettsia conorii] MLQLNIIRRIKMTKSITTSIRLEINLSKKLEKATYDLHREKSWIISEAYLKQLENSDLAK EAKRQSLLASKENNPDANLW LKHNEESWLDEWK >gi|15891929|ref|NP_359643. 1| unknown [Rickettsia conorii] MLLGVISGDYGKPRPAWWQSNLYKNHPSITVCLHNGFNRCPTTFHLLLTPTELNGFNLES HIMVDEISAIRSDKIQKNW ------------------------------------------------------------ ------------- >gi|15676809|ref|NP_273954. 1| pemI protein [Neisseria meningitidis MC58] MLRVQKWGNSAAVRLPADMLKQLDFKIGDALVAEVHNGELRVRAARRFRLADLLAEMEET PPRVEGWEILDDAGNEW >gi|15676808|ref|NP_273953. 1| pemK protein [Neisseria meningitidis MC58] MYIPDKGDIFHLNFDPSSGKEIKGGRFALALSPKAFNRATGLVFACPISQGNAAAARSSG MISTLLGAGTETQGNVHCHQ LKSLDWQIRKASFKETVPDYVLDDVLARIGAVLFD LKSLDWQIRKASFKETVPDYVLDDVLARIGAVLFD >gi|15677860|ref|NP_275028. 1| protein [Neisseria meningitidis MC58] MILNIRKMGNSQGVILPKSLLGQIGAVDSLAVTVEKGNIILSCPTVRRGWAEAAAMLVET EQEHFFSEIENEADKEWIW >gi|15677861|ref|NP_275029. 1| PemK-related protein [Neisseria meningitidis MC58] MDMVVRGGIYLVSLDPTVGSEIKKTRPCWWSPPEIHNYLKTVLIVPMTSGSRPAPFRVNV RFQDKDGLLLPEQIRAVDK AGLVKHLGNLDNSTAEKLFAVLQEMFA AGLVKHLGNLDNSTAEKLFAVLQEMFA >gi|15793408|ref|NP_283230. 1| protein NMA0401 [Neisseria meningitidis Z2491] MILNIRKMGNSQGVILPKSLLGQIGAVDSLAVTVEKGNIILSCPTVRRGWAEAAAMLVET EQEHFFSEIENEADKEWIW >gi|15793407|ref|NP_283229. 1| PEMK-like protein [Neisseria meningitidis Z2491] MVVRGGIYLVSLDPTVGSEIKKTRPCWWSPPEIHNYLKTVLIVPMTSGSRPAPFRVNVRF QDKDGLLLPEQIRAVDKAG LVKHLGNLDNSTAEKLFAVLQEMFA LVKHLGNLDNSTAEKLFAVLQEMFA >gi|30248978|ref|NP_841048. 11 protein [Nitrosomonas europaea ATCC 19718]

MLQTLRKAGGSLVMTVPKSFIEQNGLSEGSQVELHLHGKKMIVEAPARPRYKLADLMAEM PKGLPRVEGWDEMSPVGLED s >gi|30248977|ref|NP_841047. 1| PemK-like protein [Nitrosomonas europaea ATCC 19718] MTYLPNRGDIVHLDFDPSSGREIKGPHFGLILSGKLFNQRGLAMICPISQGAAAAARTYG TWTLMGAGTDTQGAVHCHQ LKSLDWQVRNVRFKESVPQHILDEVLARVEAILFE >gi|30249168|ref|NP_841238. 1| Helix-turn-helix protein, CopG family [Nitrosomonas europaea ATCC 19718] MRNTMTHRVTITLDAETFAFLNDVASSNRSAYVNQLLKQDRKNFLQAALRKANQEEAEDT NYQEKLQAWESTLSDGLAND >gi|30249167|ref|NP_841237. 11 PemK-like protein [Nitrosomonas europaea ATCC 19718] MTDFKQRDIYWIDLEPTKGAETRKLRPCVIIQSDLVNVQSRTVIVAPLLLQHKPWPFAVN LEPTEKNGLDKDRHINLKQL RAVDISRIGKKQGRLENRYKDPIKAALMIIFDL RAVDISRIGKKQGRLENRYKDPIKAALMITFDL >gi|30249549|ref|NP_841619. 1| Helix-turn-helix protein, CopG family [Nitrosomonas europaea ATCC 19718] MSQTKVAITIEEEVLARVDALVRQRVFANRSRAIQEAVQEKLERMDRSRLAEECAKLDPA FEKAMADEGLSEELVAWPKY >gi30249548JrefNP841618. 11 PemK-like protein [Nitrosomonas europaea ATCC 19718] MAKILRGEIRWANLNPTVGREQSGERPILVLSQDIFNERSGTVIAMALTSQEQRAGFPLT YEILKSSLPKRSWVKISQIR TLSTERIGKKIGAIAPEELAQIVEGLNEIIGS TLSTERIGKKIGAIAPEELAQIVEGLNEIIGS >gi|30249286|ref|NP_841356. 1| [Nitrosomonas europaea ATCC 19718] MNSHRGQMMSKDATALLHVTCVFRHNVACNASGGLHMGTTHVNARVKKHRDTLRMAGLRP VQIWVPDTRRPDFAEECRRQ CLLIAQADKADTSMQQFMDEALADSDGWTE >gi|30249285|ref|NP_841355. 11 [Nitrosomonas europaea ATCC 19718] MIRGDLVTIAVPGDFGKPGFALVIQANLFSEHTSVTVLPVTSMLVAAPLLRITVQPGAEN GLQKPSQVMVDKIITVKRDK VGPVLGCIDPDTMVEIERCLAVFLGIAK >gi|16130690|ref|NP_417263. 1| suppressor of inhibitory function of ChpA, PemI-like, autoregulated [Escherichia coli K12] MIHSSVKRWGNSPAVRIPATLMQALNLNIDDEVKIDLVDGKLIIEPVRKEPVFTLAELVN DITPENLHENIDWGEPKDKE VW >gil6130689refNP417262. 1 probable growth inhibitor, PemK-like, autoregulated [Escherichia coli K12] MVSRYVPDMGDLIWVDFDPTKGSEQAGHRPAVVLSPFMYNNKTGMCLCVPCTTQSKGYPF EVVLSGQERDGVALADQVKS IAWRARGATKKGTVAPEELQLIKAKINVLIG TAWRARGATKKGTVAPEELQLIKAKINVLIG >gi|16132046|ref|NP_418645. 1| suppressor of inhibitory function of ChpB, Peml-like, autoregulated [Escherichia coli K12] MQMRITIKRWGNSAGMVIPNIVMKELNLQPGQSVEAQVSNNQLILTPISRRYSLDELLAQ CDMNAAELSEQDVWGKSTPA GDEIW >gi|16132047|ref|NP_418646. 1| probable growth inhibitor, PemK-like, autoregulated [Escherichia coli K12] MVKKSEFERGDIVLVGFDPASGHEQQGAGRPALVLSVQAFNQLGMTLVAPITQGGNFARY AGFSVPLHCEEGDVHGWLV NQVRMMDLHARLAKRIGLAADEWEEALLRLQAWE NQVRMMDLHARLAKRIGLAADEWEEALLRLQAWE >gi|15832897|ref|NP_311670. 11 suppressor of ChpA inhibitory function [Escherichia coli 0157 : H7] MIHSSVKRWGNSPAVRIPATLMQALNLNIDDEVKIDLVDGKLIIEPVRKEPVFTLAELVN DITPENLHENIDWGEPKDKE VW >gi|15832896|ref|NP_311669. 1| PemK-like cell growth regulatory protein ChpA [Es- cherichia coli 0157 : H7] MVSRYVPDMGDLIWVDFDPTKGSEQAGHRPAVVLSPFMYNNKTGMCLCVPCTTQSKGYPF EVVLSGQERDGVALADQVKS IAWRARGATKKGTVAPEELQLIKAKINVLIG IANRARGATKKGTVAPEELQLIKAKINVLIG >gi|15834456|ref|NP_313229. 1| suppressor of inhibitory function of ChpB [Escherichia coli 0157 : H7] MQMRITIKRWGNSAGMVIPNIVMKELNLQPGQSVEVQVSNNQLILTPISRRYSLDELLAQ CDMNAAELSEQDVWGKSTPA GDEIW >gi|15834457|ref|NP_313230. 1| probable growth inhibitor [Escherichia coli 0157 : H7] MVKKSEFERGDIVLVGFDPASGHEQQGAGRPALVLSVQAFNQLGMTLVAPITQGGNFARY AGFSVPLHCEEGDVHGVVLV

NQVRMMDLRARLAKRIGLAADEWEEALLRLQAWE NQVRMMDLRARLAKRIGLAADEWEEALLRLQAWE >gi|15803304|ref|NP_289337. 1l suppressor of inhibitory function of ChpA, Peml-like, autoregulated [Escherichia coli 0157 : H7 EDL933] MIHSSVKRWGNSPAVRIPATLMQALNLNIDDEVKIDLVDGKLIIEPVRKEPVFTLAELVN DITPENLHENIDWGEPKDKE VW >gi|15803303|ref|NP_289336. 1| probable growth inhibitor, PemK-like, autoregulated [Escherichia coli 0157 : H7 EDL933] MVSRYVPDMGDLIWVDFDPTKGSEQAGHRPAWLSPFMYNNKTGMCLCVPCTTQSKGYPFE WLSGQERDGVALADQVKS IAWRARGATKKGTVAPEELQLIKAKINVLIG IAWRARGATKICGTVAPEELQLIKAKINVI, IG >gi|15804815|ref|NP_290856. 1| suppressor of inhibitory function of ChpB, PemI-like, autoregulated [Escherichia coli 0157 : H7 EDL933] MQMRITIKRWGNSAGMVIPNIVMKELNLQPGQSVEVQVSNNQLILTPISRRYSLDELLAQ CDMNAAELSEQDVWGKSTPA GDEIW >gi|15804816|ref|NP_290857. 1| probable growth inhibitor, PemK-like, autoregulated [Escherichia coli 0157 : H7 EDL933] MVKKSEFERGDIVLVGFDPASGHEQQGAGRPALVLSVQAFNQLGMTLVAPITQGGNFARY AGFSVPLHCEEGDVHGWLV NQVRMMDLRARLAKRIGLAADEWEEALLRLQAWE >gi24114677refNP709187. 1 AGRC1711p [Agrobacterium tumefaciens] [Shigella flex- neri 2a str. 301] MQTVKLRQQGGAMIVTIPRDLAIDLGWSPGTELTVEKKGDSVNLRATEHKPRGRLTVAQL LSQIDESEITELNQSTEGWA EGKKGNEAW >gi|24114678|ref|NP_709188. 11 PemK protein [Shigella flexneri 2a str. 301] MVKARTPHRGEIWYFNPDPVAGHELQGPHYCIWTDKKLNNVLKVAMCCPISTGANAARST GVTVNVLPRDTQTGNLHGV VLCHQLKAVDLIARGAKFHTVADEKLISEVISKLVNLIDPQ VLCHQLKAVDLIARGAKFHTVADEKLISEVISKLVNLIDPQ >gi|15838461|ref|NP_299149. 1| protein [Xylella fastidiosa 9a5c] MTSTHRPDSKIVHHREQMRAAGLRPVQLWVPDTRTPEFAAEIQSQCRALKGDQAEADALR FTEKAMTHIEDWK >gi15838460ref) NP299148. 1 [Xylella fastidiosa 9a5c] MEMIQRGDLVTVSLQGDYGKPRPALIVQSDLLTELDSVALCPVTSDLRNAIFRVTVEPTA ANGLRTLSQVMVDKISTLPR NKISEPFGRLNDERMKAIERALLLIIGII >gi|26987506|ref|NP 742931. 1| PemI-like protein [Pseudomonas putida KT2440] MQIKIQQWGNSAAIRLPAAVLKQMRLGVGSTLSLDTTGETMVLKPVRSKPKYTLEELMAQ CDLSAPEPEDMADWNAMRPV GREV >gi26987507refINP_742932. 1 transcriptional regulator, PemK family [Pseudomonas putida KT2440] MKRLKFARGDIVRVNLDPTVGREQQGSGRPALVLTPAAFNASGLAVIIPITQGGDFARHA GFAVTLSGAGTQTQGVMLCN QVRTVDLEARFAKRIESVPEAVILDALARVQTLFD >gi|24214480|ref|NP_711961. 1| probable ppGpp-regulated growth inhibitor suppressor ChpR/MazE [Leptospira interrogans serovar lai str. 56601] MESIIQKWGNSLGIRIPKAMATELELNDGSHVELQYEGDKIVIYPMKKASLEDKLSKITK QNLHSEISTGNSIGNEAW >gi|24214481|ref|NP_711962. 1| probable ppGpp-regulated growth inhibitor ChpA/MazF [Leptospira interrogans serovar lai str. 56601] MVKNRNYTPEKGDIVWLNFTPQAGHEQKGRRPALVLSPKEYNSKTGLAIFCPITSKIKGY PFEVLIKSKKIDGVILSDQV KNLDWTIREAEFIESINKVSLKEVLDNIKLLIF KNLDNTIREAEFIESINKVSLKEVLDNIKLLIF >gi|24215544|ref|NP_713025. 11 ChpI protein [Leptospira interrogans serovar lai str. 56601] MKTAISIPDELFRAAEKIAKKLGIPRSQLFAKALEEFIQSHSKESVTEKLNKIYSNKSKE TRNNITDLSVESLRKSLKND sw >gi|24215543|ref|NP_713024. 11 chpK [Leptospira interrogans serovar lai str. 56601] MIRGEIWWVDLGIPFGSEPGFKRPVLIIQDDSFNQSNINTIVSIAITSNLNLSEAPGNVF ISKKDSSLSKDSVINVSQIV TLDKERFLNKAGKLKSNKLGEVEIGLKLVTGLD

>gill58054431refINP-294139. 11 PpGpp-reguiated growth inhibitor suppressor ChpR/MazE, [Deinococcus radiodurans] MTSQIQKWGNSLALRIPKALAQQVGLTQSSEVELLLQDGQIVIRPVPARQYDLAALLAEM TPENLHGETDWGALEGREEW >gi|15805444|ref|NP_294140. 1| ppGpp-regulated growth inhibitor ChpA/MazF, [Deinococ- cus radiodurans] MVSDYVPDAGHLVWLNFTPQAGHEQGGRRPALVLSPAAYNGVTGLMQACPVTSRAKGYPF EVTLPAHLGVSGVVLADHCR SLDWRSRRAEQLAEAPADVLAEVRGKLGSLLGMSEKA SLDWRSRRAEQLAEAPADVLAEVRGKLGSLLGMSEKA >gi|15805688|ref|NP_294384. 1| protein [Deinococcus radiodurans] MTYQNAERMTISLPPDIARYIKDYQQTHGLESRSEAFVKAVQALREQELAEQYTALAREN DPERALFLEGNTDGLEPSDG SEWL >gi|15805689|ref|NP_294385. 1| [Deinococcus radiodurans] MAVGLIRRGDIFLTHFGPARAGEPDFKRPAWITNNVANAKADAVTVIPLTSNLETLYDFQ LLLPTERTGLNLDSKAQTE LISCIAISRIGKHLGQVPADLMAELDARIRLHLAL The following sequences were found in a later supplementary search : >mazE|28209834 : c2670080-2670397, length 116, Clostridium tetani_E88, MazE MAGSKRVGVSLSETLNNEFNKALKEDSKKRSEFIRELIILYIEDKKKLREIEQMKKGYLE MGKLNLEIAEVGFASDINSLKEYEAKLSESDWSDDNDSEKRRYILC >mazF|28209834 : c2669764-2670117, length 118, Clostridium tetani_E88, MazF MTTIVKRGDI YYASLSPWG SEQGGIRPVI IIQNDVGNRY SPTVIVAAITSQ INKAKLPTHV EISSEEYGLN KDSWLLEQI RTLDKRRLKE KIGRMTNGDM RKVDDALLVSIG LKEK ------------------------------------------------------------ ------- >mazE15607142 : c547345-547515, length 57, MycobacteriumtuberculosisH37Rv, mazE MTTYYYVLLSVTTWVGLRHEAKRELVYRGRRSIGRMPREWACRRSRRFAANGVDAAR >mazF|15607142 : c547077-547355, length 93, Mycobacterium tuberculosis_H37Rv, mazF MLRGEIWQVDLDPARGSAANMRRPAVIVSNDRANAAAIRLDRGWPWPVTSNTEKVPIP GWAGSERWPGRRFEGAGPAGWIRRCATSPLPS GWAGSERNPGRRFEGAGPAGNIRRCATSPLPS >mazF|15607142 : 2320829-2321059, length 77, MycobacteriumtuberculosisH37Rv, mazE MSTSTTIRVSTQTRDRLAAQARERGISMSALLTELAAQAERQAIFRAEREASHAETTTQA VRDEDREWEGTVGDGLG >mazF|15607142 : 2321055-2321462, length 136, Mycobacterium tuberculosis_H37Rv, mazF MAEPRRGDLWLVSLGAARAGEPGKHRPAWVSVDELLTGIDDELVWVPVSSSRSRTPLR PPVAPSEGVAADSVAVCRGVRAVARARLVERLGALKPATMRAIENALTLILGLPTGPERG EAATHSPVRWTGGRDP EAATHSPVRWTGGRDP Homoloques of ccdAB toxin-antitoxin system Polypeptides >gi|30249070|ref|NP_841140. 1| [Nitrosomonas europaea ATCC 19718] MPTIQSVRRTQSGRPGKRAINLSLSADVLDAARQLDINISQVCDTYLREWRHEQERRWRE EHADFITAYNATIEAENLP LDEWRSF >gi30249069 refNP841139. l) CcdB-like protein [Nitrosomonas europaea ATCC 19718] MARFDVYVNPGSHAATTPYLLDVQSDLLDVLDSCMVIPLRSLEHFPKVKLPGRLTPWTIK GQDFLLETPKMGAIPRRLL TMPVLSLRDMQPEITSALDFLFHGY TMPVLSLRDMQPEITSALDFLFHGY >gi|26245972|ref|NP_752011. 1| antitoxin of gyrase inhibiting toxin-antitoxin system [Escherichia coli CFT073] MTAKRTTQSVTVTVDRELVNRARDAGLNMSATLTVALNAELKKHAATRWREENAEAIAAL NQLADETGCFSDEYRSF >gi|26245973|ref|NP_752012. 1| toxin of gyrase inhibiting toxin-antitoxin system [Es- cherichia coli CFT073] MQFTVYRSRGRNAAFPFVIDVTSDIIGEINRRIVIPLTPIERFSRIRPPERLNPILLLVD GKEYVLMTHETATVPVNALG TKFCDASAHRTLIKGALDFMLDGI TKFCDASAHRTLIKGALDFMLDGI >gi|15829306|ref|NP_308079. 1| CcdA-like protein [Escherichia coli 0157 : H7] MTAKRTTQSVTVTVDRELVNRARDAGLNMSATLTVALNAELKKHAATRWREENAEAIAAL NQLADETGCFSDEYRSF >gi|15829307|ref|NP_308080. 11 CcdB-like protein [Escherichia coli 0157 : H7] MQFTVYRSRSRNAAFPFVIDVTSDIIGVINRRIVIPLTPIERFSRIRPPERLNPILLLVD GKEYVLMTHETATVPVNALG TKFCDASAHRTLIKGALDFMLDGI >gi15799732refNP_285744. 1 antitoxin of gyrase inhibiting toxin-antitoxin system [Escherichia coli 0157 : H7 EDL933] MTAKRTTQSVTVTVDRELVNRARDAGLNMSATLTVALNAELKKHAATRWREENAEAIAAL NQLADETGCFSDEYRSF >gi|15799733|ref|NP_285745. 11 toxin of gyrase inhibiting toxin-antitoxin system [Es- cherichia coli 0157 : H7 EDL933]

MQFTVYRSRSRNAAFPFVIDVTSDIIGVINRRIVIPLTPIERFSRIRPPERLNPILLLVD GKEYVLMTHETATVPVNALG TKFCDASAHRTLIKGALDFMLDGI >gi|21230189|ref|NP_636106. 11 [Xanthomonas campestris pv. campestris str. ATCC 33913] MTMRIHAHSVRMNDGMPIMSRYYDTSAQKKPLNLTINSDLAAQARAMTGNLSAKVEELLA DYVTKERDSHSARAMELQRA ASEWKTFTDAHGSFADEFSTL >gi21230188refNP_636105. 1 [Xanthomonas campestris pv. campestris str. ATCC 33913] MTDQFDVYANVGQNKNIPYWWQSKIFDASPRRVVVPLVRKSTHSPTPSRFTPELTVSGHS VILQPLEMTSVPLAALSK PAGSLKDQGQTIIDALDELFTRSFG Key to Sequence data SEQ ID NO: 1-2: ReIBE polypeptide sequences published in Gotfredsen M, Gerdes K. The Escherichia coli relBE genes belong to a new toxin-antitoxin gene family. Mol Microbiol. 1998 Aug; 29 (4) : 1065-76.

SEQ ID NO: 3-4: ReIBE polypeptide sequences published in Groniund H, Gerdes K.

Toxin-antitoxin systems homologous with relBE of Escherichia coli plasmid P307 are ubiquitous in prokaryotes. J Mol Biol. 1999 Jan 29; 285 (4): 1401-15.

SEQ ID NO: 5-16: ReIBE polypeptide sequences published in Christensen SK, Gerdes K. RelE toxins from bacteria and Archaea cleave mRNAs on translating ri- bosomes, which are rescued by tmRNA. Mol Microbiol. 2003 Jun; 48 (5): 1389-400.

SEQ ID NO: 17-97: RelE toxin polypeptide core sequences, characterised in that said sequences produce an E value of 10-1° or less when compared to one or more of SEQ ID : 2,4, 6,8, 10,12, 14 and/or 16 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

SEQ ID NO: 98-103: VapBC sequences published in Radnedge L, Davis MA, Youn- gren B, Austin SJ."Plasmid maintenance functions of the large virulence plasmid of Shigella flexneri". J Bacteriol. 1997 Jun; 179 (11): 3670-5.

SEQ ID NO: 104-105: VapBC sequences published in Pullinger GD, Lax AJ."A Salmonella dublin virulence plasmid locus that affects bacterial growth under nutri- ent-limited conditions"Mol Microbiol. 1992 Jun; 6 (12): 1631-43 SEQ ID NO: 106-154: VapC toxin polypeptide core sequences, characterised in that said sequences produce an E value of 10-1° or less when compared to one or more of SEQ ID : 99,101, 103 and/or 105 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

SEQ ID NO: 155-156: MazEF sequences published in Bravo et al., 1987 "Kis/Peml antitoxin of R1/R100" SEQ ID NO: 157-160: MazEF sequences published in Masuda et al., 1993.

SEQ ID NO: 161-205: MazF toxin polypeptide core sequences, characterised in that said sequences produce an E value of 10-1° or less when compared to one or more

of SEQ ID : 155 and/or 160, using the BLAST algorithm version (2.04) set to the de- fault parameters defined herein.

SEQ ID NO: 206-207: parDE sequences published in Roberts RC, Helinski DR.

"Definition of a minimal plasmid stabilization system from the broad-host-range plasmid RK2"J Bacteriol. 1992 Dec; 174 (24): 8119-32.

SEQ ID NO: 208-219 : ParE toxin polypeptide core sequences, characterised in that said sequences produce an E value of 10-1° or less when compared to SEQ ID : 207 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

SEQ ID NO: 220-221: higBA sequences published in Tian QB, Ohnishi M, Tabuchi A, Terawaki Y. A new plasmid-encoded proteic killer gene system: cloning, se- quencing, and analyzing hig locus of plasmid Rts1. Biochem Biophys Res Commun.

1996 Mar 18; 220 (2): 280-4.

SEQ ID NO: 222-240: HigB toxin polypeptide core sequences, characterised in that said sequences produce an E value of 10-1° or less when compared to SEQ ID : 221 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

SEQ ID NO: 241-242: Phd/Doc sequences published in Lehnherr H, Maguin E, Jafri S, Yarmolinsky MB. Plasmid addiction genes of bacteriophage P1 : doc, which causes cell death on curing of prophage, and phd, which prevents host death when prophage is retained. J Mol Biol. 1993 Oct 5; 233 (3): 414-28.

SEQ ID NO: 243-257: Doc toxin polypeptide core sequences, characterised in that said sequences produce an E value of 10-1° or less when compared SEQ ID : 242 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

SEQ ID NO: 258-259: CcdAB sequences published in Miki T, Yoshioka K, Horiuchi T. Control of cell division by sex factor F in Escherichia coli. 1. The 42.84-43. 6 F segment couples cell division of the host bacteria with replication of plasmid DNA. J Mol Biol. 1984 Apr 25 ; 174 (4): 605-25.

SEQ ID NO: 260-263: CcdB toxin polypeptide core sequences, characterised in that said sequences produce an E value of 10-1° or less when compared to SEQ ID : 259 using the BLAST algorithm version (2.04) set to the default parameters defined herein.

SEQ ID NO: 1 RelB of E. coli K-12 has experimentally verified antitoxin activity: >gi#16129523#ref#NP_416082.1# negative regulator of translation [Escherichia coli K12] MGSINLRIDDELKARSYAALEKMGVTPSEALRLMLEYIADNERLPFKQTLLSDEDAELVE IVKERLRNPKPVRVTLDEL SEQ ID NO: 2 RelE of E. coli K-12 has experimentally verified toxin activity: >gi|16129522|ref|NP_416081. 1| orf, hypothetical protein [Escherichia coli K12] MAYFLDFDERALKEWRKLGSTVREQLKKKLVEVLESPRIEANKLRGMPDCYKIKLRSSGY RLVYQVIDEKVVVFVISVGK RERSEVYSEAVKRIL SEQ ID NO: 3 RelB of E. coli plasmid P307 (ORF7) has experimentally verified antitoxin toxin ac- tivity: >gil516610 mpniilsdts asvselkknp matvsagdgf pvailnrnqp afycvpaely ekmldalddq elvklvaers nqplhdvdld kyl SEQ ID NO: 4 RelE of E. coli plasmid P307 (ORF6) has experimentally verified toxin activity: >gil516611 mryqvkfred alkewqkldk aiqqqfakkl kkccdnphip saklrgikdc ykiklrasgf rlvyqvideq liiawavgk rersdvynla sermr SEQ ID NO: 5 RelB#2 of M. jannaschii predicted from DNA sequence, Length 53.

MRLKKRFKKF FISRKEYEKI EEILDIGLAK AMEETKDDEL LTYDEIKELL GDK SEQ ID NO: 6 RelE&num 2 of M. jannaschii, exp. verified toxin activity Length: 88 >gil15669291 MKVLFAKTFV KDLKHVPGHI RKRIKLIIEE CQNSNSLNDL KLDIKKIKGY HNYYRIRVGN YRIGIEVNGD TIIFRRVLHR KSIYDYFP SEQ ID NO: 7 RelB#3 of M. jannnaschii predicted from DNA sequence, Length: 61 MSIVQSYITD EKGNIKGVIL DYKTFKKIEE LLLDYGLLKA MEEVENEEEI DLETAKKLLE Q SEQ ID NO: 8 RelE#3 of M. jannaschii, exp. verified toxin activity, Length: 91 >gil15669099 MKQWKYLLKK SFIKDLKELP KNIQEKIKKL VFEEIPNKNN PPEIPNVKKL KGADSYYRIR VGDYRIGFKY ENGKIVFYRV LHRKQIYKRF P SEQ ID NO: 9 RelB#4 of M. jannnaschii predicted from DNA sequence, Length: 84 >gil15669361 milmvkaivd itdennriin ivkakynlrd ksqainkiie eyaefllede lkpeyiekir nimknekpiy igsienlkkr ylge SEQ ID NO : 10 RelE#4 of M. jannaschii, exp. verified toxin activity, Length: 94 >gil15669362 myeieimpsl dkilqklskr dkkklkailk kmeeitqnph hyknlrhpln dfkrvhidks fvlvftvden nktvifvdfd hhdniykkkk lfkd SEQ ID NO : 11 RelB#2 of Streptococcus pneumoniae R6 predicted from DNA sequence, Length 100 >gil15903147 mtehlksntm vlplkkgaqk mttitlkvse adktfmkama kfegvslsel irtktleale deydarvadl ayqeyledle kgvepitwee mmhdlglkde SEQ ID NO : 12 RelE#2 of Streptococcus pneumoniae R6, exp. verified toxin activity, Length: 87 >gil15903146 MNNLYKLVPT RRFIKQLKKL DRYTQKLITN YLQTNVLEDP RRHGKALVGN RVGQWRYRIG NYRVIVQIVD DELWATLEV GHRRDIY

From Grady R, Hayes F. Axe-Txe, a broad-spectrum proteic toxin-antitoxin system specified by a multidrug-resistant, clinical isolate of Enterococcus faecium. Mol Microbiol. 2003 Mar; 47 (5): 1419-32.

SEQ ID NO: 13 RelB/Axe of plasmid pRUM of Enterococcus faecium, antitoxin, Length 89 >gil32470465 meavaysnfr qnlrsymkqv nedaetlivt skdvedtwv lskrdydsmq etlrtlsnny vmekirrgde qfskgafkth dlievesdd SEQ ID NO : 14 RelE/Txe of plasmid pRUM of Enterococcus faecium, toxin, Length 85 >gil32470464 mikawsddaw ddylywheqg nksnikkink likdidrspf aglgkpeplk hdlsgkwsrr itdehrliyr venetifiys akdhy SEQ. ID NO : 15 RelBIII/YefM of E. coli K-12, antitoxin, Length 83 (or 92) >gi16129958 mnctkeeidm rtisysearq nlsatmmkav edhapilitr qngeacvlms leeynsleet ayllrspana rrlmdsidsl ksgkgtekdi ie SEQ ID NO: 16 RelEIII/YoeB of E. coli K-12, toxin, Length 84 >gi#16127994 : c2087233-2087487 MKLIWSEESWDDYLYWQETDKRIVKKINELIKDTRRTPFEGKGKPEPLKHNLSGFWSRRI TEEHRLVYAVTDDSLLIAACRYHY RelE core sequences : SEQ ID NO : 17 >gi|11498679|ref|NP_069907. 1| conserved hypothetical protein [Archaeoglobus fulgidus DSM 4304] MAWKVRYHKKAIKFLEKLDEGKRSILLSKIQELVNSLESGVLPIQRMDIKRLKGVWDGFL RLRVGEVRIIFKINVEDETI FIYSIHFREKVY SEQ ID NO : 18 >gill498684refNP069912. 1j hypothetical protein [Archaeoglobus fulgidus DSM 4304] MNEVLIHKKFLDGLDSGRRSKVLDAIRMLKDFPIIRADIKKIGPKTYRLRKGEIRIIFDF DIGTNRVFVKFAASEGVFTK TEEKFF SEQ ID NO : 19 >gi|11498693|ref|NP_069922. 1| conserved hypothetical protein [Archaeoglobus fulgidus DSM 4304] MNYKAQFSEEFLKIAKKLKEKDPELLKRLQSKVEEIIKQPEHYKPLRGQMKGLRRAHVGK FVIIFKVEEDTVKFVTFKHH NHAYK SEQ ID NO : 20 >gi|11499923|ref|NP_071167. 1| conserved hypothetical protein [Archaeoglobus fulgidus DSM 4304] MFRWVHRKATQELKRLKKAHLKKFGVLLETLKTDPIPWKRFDVKKIEGEENTYRIRIGDF RVIYFLDKPTKTVHILKVE RRGKVYD SEQ ID NO : 21 >gi 14590322JrefNP142388. 1 hypothetical protein [Pyrococcus horikoshii] MTYRVKIHKQWKALQSLPKAHYRRFLEFRDILEYEPVPREKFDVIKLEGTGDLDLYRARL GDYRVIYSVNWKDKVIKIL KLKPRGRAYK SEQ ID NO : 22 >gi|14590326|ref|NP_142392. 11 hypothetical protein [Pyrococcus horikoshii] MKFEVIILPKVSKKSKKYLSKSQLEKLSKFFKTLEFDPLPVERYDVKPVKGKRSEIGKGK LYRFRIGDYRVFYTILWDEK AWIVDIKSREKAYKK SEQ ID NO : 23 >gi|15601088|ref|NP_232719. 1| conserved hypothetical protein [Vibrio cholerae] MSLLKAKLSMYKLEYSTQFKKDFKKITKMPISDIIEVGNVISKLQRGEKLEPKNVDHPLT GNWVGFRDCHIKPDLVLIYR VFNDQLQLARIGSHSDLF SEQ ID NO : 24 >gi|15601207|ref|NP_232838. 1| relE protein [Vibrio cholerae] MTYKLEFKKSALKEWKKLAVPLQQQFKKKLIERLENPHVPSAKLSGAENIYKIKLRQSGY RLVYQVENDIIWTVLAVGK RERSEVYTKALQRLDD SEQ ID NO : 25

>gill56012391reflNP_232870. 11 conserved hypothetical protein [Vibrio cholerae] MMTYKLKFLPAAQKEWSKLAPTIQSQFKKKLKERLENPHVPSAKLRGYDAVYKIKLRTAG YRLAYEVIDDEIWYVLAVG KRDKDAVYKKLASRFG SEQ ID NO : 26 >gi|15608386|ref|NP_215762. 1| hypothetical protein Rv1246c [Mycobacterium tuberculo- sis H37Rv] MSDDHPYHVAITATAARDLQRLPEKIAAACVEFVFGPLLNNPHRLGKPLRNDLEGLHSAR RGDYRWYAIDDGHHRVEII HIARRSASYRMNPCRPR SEQ ID NO : 27 >gi|15610003|ref|NP 217382. 1| hypothetical protein Rv2866 [Mycobacterium tuberculosis H37Rv] MPYTVRFTTTARRDLHKLPPRILAAWEFAFGDLSREPLRVGKPLRRELAGTFSARRGTYR LLYRIDDEHTTVVILRVDH RADIYRR SEQ ID NO : 28 >gi|15610494|ref|NP_217875. 1| hypothetical protein Rv3358 [Mycobacterium tuberculosis H37Rv] MRSVNFDPDAWEDFLFWLAADRKTARRITRLIGEIQRDPFSGIGKPEPLQGELSGYWSRR IDDEHRLVYRAGDDEVTMLK ARYHY SEQ ID NO : 29 >gi|15611892|ref|NP_223543. 1| putative [Helicobacter pylori J99] MLEIELKKKFTKDLKKHILNQKIELEVFDLWENLRNQIPLDKRFKDHALSGTYKGCRERH IKPDVLLVYRVKGNVLTLV RLGSHSELFCKPPTPLITLK SEQ ID NO : 30 >gi|15611898|ref|NP_223549. 1| putative [Helicobacter pylori J99] MLTIETSKKFDKDLKILVKNGFDLKLLYKWGNLATEQPLEPKYKDHPLKGALKDFRECHL KPDLLLVYQIKKQENTLFL VRLGSHSELF SEQ ID NO : 31 >gi|15645510|ref|NP_207685. 1| conserved hypothetical protein [Helicobacter pylori 26695] MLTIETSKKFDKDLKILVKNGFDLKLLYKVVGNLATEQPLAPKYKDHPLKGGLKDFRECH LKPDLLLVYQIKKQENTLFL VRLGSHSELF SEQ ID NO : 32 >gi|15645512|reflNP_207687. 1| conserved hypothetical protein [Helicobacter pylori 26695] MLKLNLKKSFQKDFDKLLLNGFDDSVLNEVILTLRKKEPLDPQFQDHALKGKWKPFRECH IKPDVLLVYLVKDDELILLR LGSHSELF SEQ ID NO : 33 >gi|15668242|ref|NP_247035. 11 conserved hypothetical protein [Methanococcus jan- naschii] MKFNVEIHKRVLKDLKDLPPSNLKKFKELIETLKTNPIPKEKFDIKRLKGSDEVYRVRIG KFRVQYWLWDDRIIIIRKI SRREGAYKNP SEQ ID NO : 34 >gi|15799930|ref|NP_285942. 1| Z0284 gene product [Escherichia coli 0157 : H7 EDL933] MNKLKYLMTLLINNTLPLPAVYKDHPLQGSWKGYRDAHVEPDWILIYKLTDKLLRFERTG THAALFG SEQ ID NO : 35 >gi|15829506|ref|NP_308279. 1| hypothetical protein [Escherichia coli 0157 : H7] MNSGQFSKDVKLAQKRHKDMNKLKYLMTLLINNTLPLPAVYKDHPLQGSWKGYRDAHVEP DWILIYKLTDKLLRFERTGT HAALFG SEQ ID NO : 36 >gi|15830321|ref|NP_309094. 11 hypothetical protein [Escherichia coli 0157 : H7] MLPILWLPSARDDLRQIITYIAKENPPAARRLKIRIETSVLPLSEHPYLYPPSERVSGLR EIVTHPNYIILYRVAASSIE IVSVTHSRRQFPFSI SEQ ID NO : 37 >gi|15831535|ref|NP_310308. 1| hypothetical protein [Escherichia coli 0157 : H7] MLPVLWLESADTDLDDITSYIARFDIDAAERLWQRLRGCVLPLSEHPYLYPPSDRVPGLR EIVAHPNYIILYRVTTSSVE WNVIHARRQFP SEQ ID NO : 38 >gi|15838657|ref|NP_299345. 11 conserved plasmid protein [Xylella fastidiosa 9a5c] MAKAKTPYRIKWRPKASEDLRDIVRYIGKNNPTRARSFGQELRDKTLPLAQHPEIGRTGR PGLPDYVRELVTHRNYIVFY RVLDETRTVEILRVKHVAQQMP SEQ ID NO : 39

>gi|15838671|ref|NP_299359. 1| conserved hypothetical protein [Xylella fastidiosa 9a5c] MREIKQLGQFKRDLKREAKGQHRATLEDDLLPVIDALAKDMPLEPRHRDHALLGNWKDLR DCHIKLDLVLIYTRVDSKTL TLVRLGSHAELGL SEQ ID NO : 40 >gi|15840691|ref|NP_335728. 1| hypothetical protein [Mycobacterium tuberculosis CDC1551] MTWRPSRKRWRCYAPLAPARPFVKASPMLPQALREQRRDPQPLHRAVSDDHPYHVAITAT AARDLQRLPEKIAAACVEFV FGPLLNNPHRLGKPLRNDLEGLHSARRGDYRWYAIDDGHHRVEIIHIARRSASYRMNPCR PR SEQ ID NO : 41 >gi|15842954|ref|NP_337991. 1| conserved hypothetical protein [Mycobacterium tubercu- losis CDC1551] MRSVNFDPDAWEDFLFWLAADRKTARRITRLIGEIQRDPFSGIGKPEPLQGELSGYWSRR IDDEHRLVYRAGDDEVTMLK ARYHY SEQ ID NO : 42 >gi|15888017|ref|NP_353698. 11 AGR_C_1206p [Agrobacterium tumefaciens] MIWTIEYHTLVQKEMRKINPEVRRRIRSFLHERLAALDDPRQIGATLQGSELGNFWRYRV GDYRIICDIQDQKLWLWE IGHRREIYR SEQ ID NO : 43 >gi|15888273|ref|NP_353954. 1| AGR_C_1701p [Agrobacterium tumefaciens] MTNKKDHGKDAALKRATLPRRSDFTKQFIKDWQRLNNSGRYDMVRLKEIMLLLIANGAPL PTQFRDHELTGDWRDHRECH VGGDFLLIYTVDEKQNLLIFTRAGTHAELFR SEQ ID NO : 44 >gi|15889305|ref|NP_354986. 1| AGR C_3658p [Agrobacterium tumefaciens] MKLVWTLSSWDDYEFWQRTDARMVEKINDLIRNAKRTPFAGLGKPEPLKGDMAGYWSRRI TAEHRFVYRVSGSGSEQRLE VIQCRFHYQ SEQ ID NO : 45 >gi|15900210|ref|NP_344814. 1| conserved hypothetical protein [Streptococcus pneumo- niae TIGR4] MLKIRYHKQFKKDFKLAMKRGLKAELLEEVLNFLVQEKEHPARNRDHSLTASKHFQGVRE CHTQPDWLLVYKVDKSELIL NLLRTGSHSDLF SEQ ID NO : 46 >gi15901085refNP_345689. 1 conserved hypothetical protein [Streptococcus pneumo- niae TIGR4] MYKLVPTRRFIKQLKKLDRYTQKLITNYLQTNVLEDPRRHGKALVGNRVGQWRYRIGNYR VIVQIVDDELWATLEVGHR RDIY SEQ ID NO : 47 >gi|15901572|ref|NP_346176. 1| conserved hypothetical protein [Streptococcus pneumo- niae TIGR4] MLLKFTEDAWADYCYWQNQDKKTLKRINKLIKDIQRDPFTGIGKPEPLKYDYQGAWSRRI DAENRLIYMMDGDSVAFLSF KDHY SEQ ID NO : 48 >gi|15902297|ref|NP_357847. 11 Conserved hypothetical protein [Streptococcus pneumo- niae R6] MLKIRYHKQFKKDFKLAMKRGLKAELLEEVLNFLVQEKEHPARYRDHSLTASKHFQGVRE CHTQPDWLLVYKVDKSELIL NLLRTGSHSDLF SEQ ID NO : 49 >gi|15903146|ref|NP_358696. 1| Hypothetical protein [Streptococcus pneumoniae R6] MNNLYKLVPTRRFIKQLKKLDRYTQKLITNYLQTNVLEDPRRHGKALVGNRVGQWRYRIG NYRVIVQIVDDELWATLEV GHRRDIY SEQ ID NO : 50 >gi|15903627|ref|NP_359177. 11 Conserved hypothetical protein [Streptococcus pneumo- niae R6] MLLKFTEDAWADYCYWQNQDKKTLKRINKLIKDIQRDPFTGIGKPEPLKYDYQGAWSRRI DAENRLIYMMDGDSVAFLSF KDHY SEQ ID NO : 51 >gi|15925397|ref|NP_372931. 11 conserved hypothetical protein [Staphylococcus aureus subsp. aureus Mu50] MARLNITFSPQAFEDYKYFQQNNKKMVKKINELLKSIDRNGALEGIGKPEKLKSNLTGYY SRRINHEHRLVYTVDDNHIK IASCKYHY SEQ ID NO : 52

>gill5927985lreflNp-3755l8. ll conserved hypothetical protein [Staphylococcus aureus subsp. aureus N315] MARLNITFSPQAFEDYKYFQQNNKKMVKKINELLKSIDRNGALEGIGKPEKLKSNLTGYY SRRINHEHRLVYTVDDNHIK IASCKYHY SEQ ID NO : 53 >giI15965227refINP 385580. 1I CONSERVED HYPOTHETICAL PROTEIN [Sinorhizobium meliloti] MRFGYRRGLEFLPSARKEWDKLGATIRQQLVKKLRERLERPRIPSAALHGMPDHYKIKLR QLGYRLVYRVDDGSVTVLW AVGKRERVTSTT SEQ ID NO : 54 >gi|16121191|ref|NP_404504. 1| hypothetical protein [Yersinia pestis] MVKVDWSRKAVKQLLSIDARYRKPISEKVNKLTNFPAVDLDIKKLQMGDSQFRMRVGNYR VIFQIVEGTPVICTIQEVKR RTTATY SEQ ID NO : 55 >gi|16128211|ref|NP 414760. 1| orf, hypothetical protein [Escherichia coli K12] MIQRDIEYSGQYSKDVKLAQKRHKDMNKLKYLMTLLINNTLPLPAVYKDHPLQGSWKGYR DAHVEPDWILIYKLTDKLLR FERTGTHAALFG SEQ ID NO : 56 >gi|16129522|ref|NP_416081. 11 orf, hypothetical protein [Escherichia coli K12] MAYFLDFDERALKEWRKLGSTVREQLKKKLVEVLESPRIEANKLRGMPDCYKIKLRSSGY RLVYQVIDEKVWFVISVGK RERSEVYSEAVKRIL SEQ ID NO : 57 >gi16272651refNP_438869. 1 hypothetical protein [Haemophilus influenzae Rd] MSEEKPLKVSYSKQFVRDLTDLAKRSPNVLIGSKYITAIHCLLNRLPLPENYQDHALVGE WKGYRDCHIQGDLVLIYQYV IQDEFDELKFSRLNIHSQTALK SEQ ID NO : 58 >gi|16332148|ref|NP_442876. 1| unknown protein [Synechocystis sp. PCC 6803] MSNNLHLVNIDFTPEYRRSLKYLAKKYRNIRSDVQPIIEALQKGVISGDRLAGFGSDIYV YKLRIKNSNIQKGKSSGYRL IYLLESENSILLLTIYSKAEQEDIAASDINSILGEYSIED SEQ ID NO : 59 >gi|16763250|ref|NP_458867. 1| conserved hypothetical protein [Salmonella enterica subsp. enterica serovar Typhi] MTYELEFDPRALKEWHKLGDTVKAQLKKKLADVLLNPRIDSARLNGLPDCYKIKLKSSGY RLVYQVRDDWIVFWAVGK REHSAVYHDANKRL SEQ ID NO : 60 >giI16764895IrefINP_460510. 1 putative cytoplasmic protein [Salmonella typhimurium LT2] MTYKLAFNESALKEWKKLGHTIQEQFKKKLRERLENPRVPASQLHGRKDQYKIKLRGAGY RLVYSVEDEIITVTVIGVGK RENDAVYKMTRHRS SEQ ID NO : 61 >gi|16766804|ref|NP_462419. 11 putative cytoplasmic protein [Salmonella typhimurium LT2] MGQREIEYSGQFQKDVKRAQKRHKDVGKLKTLMTLLIHHPFPLPAIYKDHPLQGSYSGYR DAHIEPDWILIYKITDECLR FERTGTHADLF SEQ ID NO : 62 >gi|16767696|ref|NP_463311. 1| putative inner membrane protein [Salmonella typhimurium LT2] MTYELEFDPRALKEWHKLGDTVKAQLKKKLADVLLNPRIDSARLNGLPDCYKIKLKSSGY RLVYQVRDDWIVFWAVGK REHSAVYHDANKRL SEQ ID NO : 63 >gi|17227667|ref|NP_484215. 11 hypothetical protein [Nostoc sp. PCC 7120] MFQPEFLEDLEFWVETNQRVALKALDLVKETCRDPFKGKGKPEPLKYLDPDTWSRRLTQE HRIVYLVKDDEINFLQARYH y SEQ ID NO : 64 >gi|17228895|ref|NP_485443. 11 hypothetical protein [Nostoc sp. PCC 7120] MPGDQIPGIGYTVFKLRVRNSDTQKGKSGGYRLIYYVKTATGIILLTVYTKSEQVDIAAD DIQSIIADYEQRTLTEQDNS SEQ ID NO : 65 >gi|17231899|ref|NP_488447. 1| hypothetical protein [Nostoc sp. PCC 7120] MSYGTELMQSDNTVSIRFSDEFEAELYRLSKRFRKIRSDVQPIIEQLQQGDFVGDRISGF GEEYFVYKVRVRNSNIQKGK SAGYRLIYQVDSPTNIVLLTIYSKSDREDIGANEIRDILADFYGDSG SEQ ID NO : 66

>gi17547996ref) NP521398. 1) CONSERVED HYPOTHETICAL PROTEIN [Ralstonia solanacearum] MNAIHWTAWAARQLRKLDRQHQRVLVEAVGQLEAMPHCRQVRALREHRYGYRLRVGDYRV LSDWDDGIRIVDIQEVSKRD ERTYRH SEQ ID NO : 67 >gi|17934584|ref|NP_531374. 11 conserved hypothetical protein [Agrobacterium tumefa- ciens str. C58 (U. Washington)] MIWTIEYHTLVQKEMRKINPEVRRRIRSFLHERLAALDDPRQIGATLQGSELGNFWRYRV GDYRIICDIQDQKLWLWE IGHRREIYR SEQ ID NO : 68 >gi|17934842|ref|NP_531632. 1| conserved hypothetical protein [Agrobacterium tumefa- ciens str. C58 (U. Washington)] MKRATLPRRSDFTKQFIKDWQRLNNSGRYDMVRLKEIMLLLIANGAPLPTQFRDHELTGD WRDHRECHVGGDFLLIYTVD EKQNLLIFTRAGTHAELFR SEQ ID NO : 69 >giI17935903IrefNP_532693. 11 conserved hypothetical protein [Agrobacterium tumefa- ciens str. C58 (U. Washington)] MKLVWTLSSWDDYEFWQRTDARMVEKINDLIRNAKRTPFAGLGKPEPLKGDMAGYWSRRI TAEHRFVYRVSGSGSEQRLE VIQCRFHYQ SEQ ID NO : 70 >gi|19703556|ref|NP_603118. 1| Plasmid addiction system poison protein [Fusobacterium nucleatum subsp. nucleatum ATCC 25586] MKYDVEYSKTAMNTIKKMDSSTSKLIRTWIEKNLINTENPRIKGKALTGDLKGLWRYRIG DYRILAEIQDDKIVILILDI GHRSKIYL SEQ ID NO : 71 >gi] 19703832refNP603394. 1 Plasmid addiction system poison protein [Fusobacterium nucleatum subsp. nucleatum ATCC 25586] MKKYEVKFSEAAIKELKKLDKPTATMIKLWVIQNLENTINPRQHGKSLTANYSGKWRYRV GNYRLLAEIYDDEILILIFK VAHRSIVYKK SEQ ID NO : 72 >gi|19704435|ref|NP_603997. 1| Plasmid addiction system poison protein [Fusobacterium nucleatum subsp. nucleatum ATCC 25586] MGYRVMIPDKVNKKILKFDRNTRKLLYDYINKNLKDTDDPRLHGKALTGNLKGLWRYRIM DYRLIVDIQDEQLIIVAVDF NHRRKIYL SEQ ID NO : 73 >gi|20090546|ref|NP_616621. 1| conserved hypothetical protein [Methanosarcina acetivorans str. C2A] MTYQVVLSPDFEKETKIFFKKDPVLYGRFKKTVNSILENPECGKPLRNVLKGLRRVHIGH FVLIYEIDNTNETITFLKFS PHDKAYK SEQ ID NO : 74 >gi|20808431|ref|NP_623602. 11 conserved hypothetical protein [Thermoanaerobacter tengcongensis] MRTCSKMYKVKLAKEAVKFTEKCNSNTKEKIKEAIEKIAQSPYVGKNIKKLKDKFPPLYR YRVGNIRIIYQIQKGEKIIF IVTIGYRGDVYK SEQ ID NO : 75 >gi|20808956|ref|NP_624127. 11 conserved hypothetical protein [Thermoanaerobacter tengcongensis] MKFEYRIIVNKKVLKELEKHDRKTVERVIKAIEKLPFEGDVKKLKTSKKEKLYRLRVGDY RIIFEVDNENFVIKVKDFDS RGDVYK SEQ ID NO : 76 >gi|21220707|ref|NP_626486. 1| conserved hypothetical protein [Streptomyces coelicolor A3 (2)] MRITFTSHGWEDYVHWAESDRKVTKRINRLIADIARDPFKGVGKPEPLKGDLSGYWSRRI DDTHRLVYKPTDDQLVIVQA RYHY SEQ ID NO : 77 >gij21284058 ref] NP647146. 1j conserved hypothetical protein [Staphylococcus aureus subsp. aureus MW2] MARLNITFSPQAFEDYKYFQQNDKKMVKKINELLKSIDRNGALEGIGKPEKLKSNLTGYY SRRINHEHRLVYTVDDNHIK IASCKYHY SEQ ID NO : 78 >gi|22538143|ref|NP_688994. 11 conserved hypothetical protein [Streptococcus agalac- tiae 2603V/R] MFNFTEEAWKDYVSWQQEDKKILKRINRLIEDIKRDPFEGIGKPEPLKYHYSGAWSRRIT EEHRLIYMIEDGEIYFLSFR

DHYK SEQ ID NO : 79 >gil24112920|ref|NP_707430. 1| orf, conserved hypothetical protein [Shigella flexneri 2a str. 301] MAYFLDFDERALKEWRKLGSTVREQLKKKLVEVLESPRIEANKLRGMPDCYKIKLRSSGY RLVYQVIDEKVWFVISVGK RERSEVYSEAVKRIL SEQ ID NO : 80 >gi|24113399|ref|NP_707909. 1| orf, conserved hypothetical protein [Shigella flexneri 2a str. 301] MKLIWSEESWDDYLYWQETDKRIVKKINELIKDTRRTPFEGKGKPEPLKHNLSGFWSRRI TEEHRLVYAVTDDSLLIAAC RYHY SEQ ID NO : 81 >gi|24379348|ref|NP_721303. 1| conserved hypothetical protein [Streptococcus mutans UA159] MLKIKQTRQFKKSLKKVVKQGKDINKLFAIVELLCQKSELPLALRNHELKGRWRGIRELH IESDWLLAYQVLDDELVLLL IDTGSHAQMLGM SEQ ID NO : 82 >gi|26248391|ref|NP_754431. 1| Hypothetical protein [Escherichia coli CFT073] MKLIWSEESWDDYLYWQETDKRIVKKINEIIKDTRRTPFEGKGKPEPLKHNLSGFWSRRI TEEHRLVYAVTDDSLLIAAC RYHY SEQ ID NO : 83 >gi|26989658|ref|NP_745083. 1| conserved hypothetical protein [Pseudomonas putida KT2440] MKFTKEGWEDYCHWQNADLTILGNINRLIDVCLRTPFTGIGKPEPLKGDLSGLWSRRITR EHRLVYFFEAGMLTVLQCRY HYDD SEQ ID NO : 84 >gi|28867567|ref|NP_790186. 1| conserved hypothetical protein [Pseudomonas syringae pv. tomato str. DC3000] MHFTLSGWDDYTHWKDADQAISLSIDSLISQCLRTPFKGTGKPRPLTGDLTGYWSRRITK EHRLVYFYEGGVLTVIACRH HY SEQ ID NO : 85 >gi|28872495|ref|NP_795114. 1| stability cassette protein, putative [Pseudomonas sy- ringae pv. tomato str. DC3000] MTYSLEFDARALKEWRKLGDTVRQQLKKKLATILVAPRVEANRLHALPDCYKIKLRSSGY RLVYQVIDQEVWFWAVDK RERDEVYRKAADRLSG SEQ ID NO : 86 >gi|28898594|ref|NP_798199. 11 hypothetical protein [Vibrio parahaemolyticus RIMD 2210633] MMSSSQRLLSWTDDAWDDYLYWQTQDKKTLKRINKLINDVKRSPFEGIGKPEPLKENLSG FWSRRIDDTNRLVYAVDDQA ITIISCRYHY SEQ ID NO : 87 >gi|29144729|ref|NP_808071. 11 conserved hypothetical protein [Salmonella enterica subsp. enterica serovar Typhi Ty2] MTYELEFDPRALKEWHKLGDTVKAQLKKKLADVLLNPRIDSARLNGLPDCYKIKLKSSGY RLVYQVRDDWIVFWAVGK REHSAVYHDANKRL SEQ ID NO : 88 >gi|29375141|ref|NP_814294. 1| conserved hypothetical protein TIGR00053 [Enterococcus faecalis V583] MLEIFYTNQFKKDFKKAKKQGKNLEKLKEVLVLLQEQQTLPPKYKDHALTGNYIGTRECH IEPDWLLIYKIDGDKLILTL ARIGSHSELFR SEQ ID NO : 89 >gi|29655275|ref|NP_820967. 1| conserved hypothetical protein [Coxiella burnetii RSA 493] MQISFTPEAWEDYLYWQKFDKKMLRRINELIKDAMHEPFSGKGKPEPLKFELQGYWSRRL DQEHRLVYKVLDDSLMIIAA RFHYNRLNSKN SEQ ID NO : 90 >gi|29829747|ref|NP_824381. 11 hypothetical protein [Streptomyces avermitilis MA-4680] MRLVFEDQGWEDYTSWLKNDRKMLARINRLIEDVKRDPFTGIGKPEPLKYHLPGVWSRRI DDEHRLVYLVTDKEWILAA RYHY SEQ ID NO : 91 >gi|30063050|ref|NP_837221. 1| hypothetical protein [Shigella flexneri 2a str. 2457T]

MAYFLDFDERALKEWRKLGSTVREQLKKKLVEVLESPRIEANKLRGMPDCYKIKLRSSGY RLVYQVIDEKVWFVISVGK RERSEVYSEAVKRIL SEQ ID NO : 92 >gi|30248567|ref|NP_840637. 1| conserved hypothetical protein [Nitrosomonas europaea ATCC 19718] MMKLFWTPEALQDRDAIYDYIEVDNPRAALALDELFSEKAQRLPDHPALGHPGRVAGTRE LIAHQNYIIIYDVTGELVRV LRVLHAARQWPPSEND SEQ ID NO : 93 >gi30248722refINP_840792. 1 conserved hypothetical protein [Nitrosomonas europaea ATCC 19718] MKLVFSEQAWEDYLYWQKTDRKTVQRIDTLVKEITRTPHEGTGKPEPLKHALSGYWSRRI NNEHRIVYKIADDSLFIAQL RYHY SEQ ID NO : 94 >gi|30249083|ref|NP_841153. 1| conserved plasmid protein [Nitrosomonas europaea ATCC 19718] MAEADLDNIIDYIAQDNPTRTEEFGQELRDKILPLTQNPKMGRTGRPGSSAFVRELVAHR NYIVFYRVLDEACTVEILRV KHAAQQSS SEQ ID NO : 95 >gi|30249324|ref|NP_841394. 1| conserved hypothetical protein [Nitrosomonas europaea ATCC 19718] MRAIRFVPDAWEAYLYWQDQDKKTLRRLNSLITAASRDPFVGIGKPEPLRGELSGYWSRR IDETNRLVYRVTDVELVIIA CRFHYE SEQ ID NO : 96 >gi|30249532|ref|NP_841602. 1| Protein of unknown function DUF79 [Nitrosomonas eu- ropaea ATCC 19718] MTYKLKFLPSAKKEWDKLDSSIKTQFKNKLKKCLENPHIQPNKLRGFDNAYKIKLRSAGY RLVYEINNQEVWFVIAVGK RENNKIYDKAINRTKT SEQ ID NO : 97 >gi|30249553|ref|NP_841623. 1| hypothetical protein [Nitrosomonas europaea ATCC 19718] MTYKLEFKKSALKEWEKLGHTIKEQFKKKLKERLENPHVHSAALPGAKNIYKIKLRQPGY RLVYSVEDQTITVTVIAIGK RDRNEIYDIALSRLHDKS SEQ ID NO : 98 STBORF1 of Shigella flexneri plasmid pMYSH6000, antitoxin, Length 75 >gil2109264 mettvflsnr sqavrlpkav alpenvkrve viavgrtrii tpagetwdew fdghsvstdf mdnreqpgmq eresf SEQ ID NO : 99 STBORF2 of Shigella flexneri plasmid pMYSH6000, toxin, Length 132 >gil2109263 mlkfmldtni ciftiknkpa svrerfnlnq gkmcissvtl meliygaeks qmpernlavi egfvsridvl dydaaaatht gqiraelarq grpvgpfdqm iagharsrgl iivtnntref ervgglrted ws SEQ ID NO : 100 Hi0321 of H. influenzae, antitoxin, Length 78 >gi16272274 mltkvfqsgn sqavripmdf rfdvdtveif rkengdwlr pvskktddfl alfegfdetf iqalearddl ppqerenl SEQ ID NO : 101 Hi0322 of H. influenzae, toxin, Length 134 >gil16272275 miymldtnii iylmknrpki iaervsqllp ndrlvmsfit yaelikgafg sqnyeqsira ielltervnv lypneqiclh ygkwantlkk qgrpignndl wfachalsln avlithnvke fqritdlqwq dwtk SEQ ID NO : 102 Hi0948 of H. influenzae, antitoxin, Length 77 >gil16272886 mieasvfmtn rsqavrlpae vrfseeikkl svrvsgsdri lsplnqswds fflndqavsd dfmnereiaf qpereal SEQ ID NO : 103 Hi0947 of H. influenzae, toxin, Length 132

>gil16272885 mlkymldtni viyvikrrpl eilsrfnqna gkmcvssitv aelyygaeks eyperniavi edflsrltil dyqpkhaahf gnikaelskq gkligendih iaaharsegl ilvsnnlref ervialrten wv SEQ ID NO : 104 Salmonella dublin virulence plasmid, antitoxin VagC >gi|49102, Length 100 mhtpgamnii pdmhhistlt rerimrtvsi fkngnnrair lprdldfegv seleivregd siilrpvrpt wgsfaqleka dpdfmaered wsdegrfel SEQ ID NO : 105 Salmonella dublin virulence plasmid, toxin VagD >gi j 49103, Length 85 mkcprtktym ldtcicsfim reqseavlkr leqavlrghr ivisaityse mrfgatgpka sprlvqlvda fcarldailp wdraa SEQ ID NO : 106 >gi|16272885|ref|NP 439108. 1| virulence-associated protein C [Haemophilus influenzae Rd] MLKYMLDTNIVIYVIKRRPLEILSRFNQNAGKMCVSSITVAELYYGAEKSEYPERNIAVI EDFLSRLTILDYQPKHAAHF GNIKAELSKQGKLIGENDIHIAAHARSEGLILVSNNLREFERVIALRTENWV SEQ ID NO : 107 >gi|32034473|ref|ZP_00134645. 1| hypothetical protein [Actinobacillus pleuropneumoniae serovar 1 str. 4074] MIKRRPIEVLDKFNLNSTRLCISSITAAELYYGAEKSQFPERNMAVIEDFLSRLTILDYT HKAATHFGNIKAHLSKQGKI IGENDIHIAAHARSEGLVLVTNNLREFERVEGLRLDNWV SEQ ID NO : 108 >gi|30248494|ref|NP_840564. 1| PIN (PilT N terminus) domain [Nitrosomonas europaea ATCC 19718] MLKYMLDTNIAIYVIKRRPIEVLVTFNRYADMMCVSAVTEAELLHGAEKSRQREHNLRQV ADFLSRLEVLSYTSKAAGHY GDIRADLERKEKPIGVNDLHIAAHARSEGFILVSNNLREFERVDGLRLENWIT SEQ ID NO : 109 >gi|13449196|ref|NP 085412. 1| plasmid maintenance protein [Shigella flexneri] MLKFMLDTNICIFTIKNKPASVRERFNLNQGKMCISSVTLMELIYGAEKSQMPERNLAVI EGFVSRIDVLDYDAAAATHT GQIRAELARQGRPVGPFDQMIAGHARSRGLIIVTNNTREFERVGGLRTEDWS SEQ ID NO : 110 >gi|17233504|ref|NP_490590. 1| MvpA-like protein [Salmonella typhimurium LT2] MLKFMLDTNICIFTIKNKPASVRERFNLNQGRMCISSVTLMELIYGAEKSQMPERNLAVI EGFVSRLDVLDYDTPAATHT GQIRAELARQGRPVGPFDQMIAGHARSRGLIWTNNTREFERVGGLRTEDWS SEQ ID NO : 111 >gi|32470009|ref|NP_862949. 1| hypothetical protein [Escherichia coli] MLKFMLDTNICIFTIKNKPASVRERFNLNQGRMCISSVTLMEVIYGAEKSQMPERNLAVI EGFVSRIDVLDYDAAAATHT GQIRAELALQGRPVGPFDQMIAGHARSRGLIIVTNNTREFERVGGLRIEDWS SEQ ID NO : 112 >gi|16761810|ref|NP_457427. 11 hypothetical protein (assiciated with virulence) [Sal- monella enterica subsp. enterica serovar Typhi] MLKFMLDTNTCIFTIKNKPEHIRERFNLNTSRMCISSITLMELIYGAEKSLAPERNFAWE GFISRLEVLDYDTQAAIHT GQIRTELARKGTPVGSYDQMIAGHARSRGLVWTNNLREFERIPGIRIEDWC SEQ ID NO : 113 >gi|16766335|ref|NP_461950. 11 putative nucleic acid-binding protein, contains PIN domain [Salmonella typhimurium LT2] MLKFMLDTNTCIFTIKNKPEHIRERFNLNTSRMCISSITLMELIYGAEKSLAPERNLAWE GFISRLEVLDYDTQAAIHT GQIRAELARKGTPVGPYDQMIAGHAGSRGLWWTNNLREFERIPGIRIEDWC SEQ ID NO : 114 >gi|28868262|ref|NP_790881. 1| virulence-associated protein, putative [Pseudomonas syringae pv. tomato str. DC3000] MLKYMLDTNICIFTIKNKPVSVREAFNLHHGQLCISAITLMELVYGAEKSSSPERNLAWE GFAARLELLPYDSDAAAHT GMIRAELARAGTPIGPYDQMIAGHARSLGLWITNNQREFQRVEGLRVEDWVSQ SEQ ID NO : 115 >gi|22959838|ref|ZP_00007484. 1| hypothetical protein [Rhodobacter sphaeroides] MLRYMLDTNILIYTIRNRPGEVRAKFEAHHGTMCISAATAMELIYGAQKSQAVERNVAAV EGLLARLDILDLDLAAAQHA GEIRAQLAQAGTPIGPFDVMIAGHARSKGLVLVSNNTREFERVDGLRLENWVQSS

SEQ ID NO : 116 >gill59664381refINE-386791. 11 CONSERVED HYPOTHETICAL PROTEIN [Sinorhizobium meliloti] MLTYMLDTNICIYVMKTYPPAVREKFNGLAEQLCISSITLGELHYGAEKSAWRVENLTAI EHFVARLEVLPFADKAAAHY GQVRAELERTGTPCGPHDMQIGAHARSEGLIWTNNIREFVRMPGVRVENWL SEQ ID NO : 117 >gi|23467534|ref|ZP_00123115. 1| hypothetical protein [Haemophilus somnus 129PT] MLKYMLDTNIAIFTIKNKPVHMLPLFNENQSMLCMSSIALMELVYGAEKSTKVAHNLAVI ESFCSRLTLLNYDDRAAYHS GQIRAELAKQGQPIGPYDAMIAGHARSLGLTIVTNNVKEFSKVEGLKWDWSK SEQ ID NO : 118 >gi|24213701|ref|NP_711182. 11 virulence associated protein C [Leptospira interrogans serovar lai str. 56601] MYLLDTNICIFLIKKKNATLLENLKKKLNKDLFVSSLTVAELEFGIQKSEFKEKNKVALI EFLTIFNILSFSDKDAESYG IIRADLERKGNVIGSIDMLLAAQAIANNYIFVTNNTKEFKRIKALKIENWTQ SEQ ID NO : 119 >gi23008383refIZP_00049852. 7. hypothetical protein [Magnetospirillum magnetotacticum] MSTLYLLDTNVLVALLRGHGAAARPRLREAEGRVAVSTASEMELEYGVERSQDPARNRQA VDELLSLVDVLPFDSLAAMH AGRVRAVLAARGTPVGPYDALLAGHARSLGLVLVTNNVREFSRVPGLEVEDWLADATHGP SEQ ID NO : 120 >gi|477904|pir||B49205 virulence-associated protein vapC-Dichelobacter nodosus MSIKLMLDTNICIYIINRKPPYIAEKFSRYEIGDIGISNITACELAFGVEKSGSAKNKTA LTKFLAPLSILPFDKQAIWH YARIRQSLQNRGTPIGALDMLIASHALALDITLVTNNTKEFERVDGLMLDNWVID SEQ ID NO : 121 >gi|16272275|ref|NP_438487. 1| virulence-associated protein C [Haemophilus influenzae Rd] MIYMLDTNIIIYLMKNRPKIIAERVSQLLPNDRLVMSFITYAELIKGAFGSQNYEQSIRA IELLTERVNVLYPNEQICLH YGKWANTLKKQGRPIGNNDLWFACHALSLNAVLITHNVKEFQRITDLQWQDWTK SEQ ID NO : 122 >gi|11277576|pir||T44272 virulence associated protein C [imported]-Synechococcus sp. (strain PCC7942) MFLLDTNACIQLLNRRHPQLLQHFRQQSPADIALCSIVKSELLYGARRSQNVEANLQLLD RFFAPLQSLPFTDRCAEEAG LIRADLAAQGKPIGPNDLLIAATARAFDTTLVTYNTREFVRITGLRWDWELANPLLS SEQ ID NO : 123 >gi|16262982|ref|NP_435775. 1| probable NtrR2 transcription regulator [Sinorhizobium meliloti] MSRLYMLDTNIVSELARNPQGAVTKRIAEVGPEAVCVSIITAAELRYGCAKKGSPKLLAQ IEAILGSMQVLALDVPADAE YGNIRAELETAGKPIGPNDLFIAAHACVLGAVLVTVNSSEFTRVRDLKVENWLDFTSSG SEQ ID NO : 124 >gi|17227400|ref|NP_478451. 1| virulence-associated protein [Nostoc sp. PCC 7120] MRYLLDTNVCARYLNGKSPAIRQRLRSTNVKDIAVCSWKAELFYGAMKSNNPERTLARQQ QFLNLFVSLPFDDVTALTY GRIRAALAISGTPIGPNDLQIAAIALVNNLILVTHNTSEFNRVNGLQIEDWEAVA SEQ ID NO : 125 >gi|15967066|ref|NP_387419. 1| PUTATIVE VIRULENCE ASSOCIATED PROTEIN HOMOLOGUE [Sinorhizobium meliloti] MISHILDTNAVIALIGRKSDALVTRVLHSPQGIIGLPSWAYELYFGAQKSAKAQHNLETL RLLMADFPILDFDRNDAFV AGEIRAALAAKGTPIGPYDVLIAGQAKARGLTLVTNNVGEFNRVENLRVEDWSL SEQ ID NO : 126 >gi|32470033|ref|NP_862975. 1| putative protein [Escherichia coli] MKKTWMLDTNICSFIMREQPAAVLKRLEQAVLRGDRIWSAVTYAEMRFGATGPKASPRHI QLVDAFCARLDAVLPWDRA AVDATTDIRVALRLAGTPIGPNDTAIAGHAIAAGAILVTNNVREFARVPGLVLEDWVK SEQ ID NO : 127 >gi|32470170|ref|NP_863394. 1| 94 pct identical to pir : S22686 [VagD of Salmonella dublin virulence plasmid] [Salmonella typhimurium] MNKTYMLDTCICSFIMREQPEAVLKRLEQAVLRGHRIWSAITYSEMRFGATGPKASPRHV QLVDEFCARLDAILPWDRA AVDATTKIKVALRLAGTPIGPNDTAIAGHAIAAGAILVTNNTREFERVPDLVLEDWVK SEQ ID NO : 128 >gi|21264287|ref|NP_644787. 1| virulence associated protein [Xanthomonas axonopodis pv. citri str. 306] MKRYMLDTNTVSHLVKSHPAVSRRVIEVPMTALCMSAITGGELMFGLAKVPDAKRLQQAV MELLRRVDVLPWDGAVMERY GSVRADLEKQGKALGSLDMLIAAHALETDSVLVTNDAAFSRWGLTVEDWTRS SEQ ID NO : 129

>gi|23467536|ref|ZP_00123117. 1| hypothetical protein [Haemophilus somnus 129PT] MIYMLDTNTVSDVIRKDPNVIRQLKSLSPESICLSGITAAEIIYGLEKRQSTKLNQVMYP FLEAVTIHDWHYGVAQCYGK LRAKMEKQGFVMGSLDLMIAAHAISENCTLVTSDNAFKMVPDLAIQNWREKHNI SEQ ID NO : 130 >gi|31075369|gb|AAP42488. 1| unknown [Escherichia coli] MLDTCICSFIMREQPEAVLKRLEQAVLRGHRIWSAITYSEMRFGATGPKASPRHVQLVDE FCARLDAILPWDRAAVDAT TKIKVALRLAGTPIGPNDTAIAGHAIAAGAILVTNNTKEFERVPDLVLEDWVK SEQ ID NO : 131 >gi|23103164|ref|ZP_00089651. 11 hypothetical protein [Azotobacter vinelandii] MPRYMLDTNMCIYLMKNQPEEWRRFAQCYVGDWISAITYAELDYGVATSANPERERINLA SLIEDIPVAPFDAAAGMA YGPIRLATRDSKKDHLDKLIAAHAVALNVILVTNNVRDFKKYPGVSIENWLEAQAE SEQ ID NO : 132 >gi|15966171|ref|NP_386524. 1| NITROGEN REGULATORY PROTEIN [Sinorhizobium meliloti] MNGYLLDTNIISDVIHNPFGPAAQRIERIGPKEIYTSIWASELRYGCAKKGSAKLLAKVE SLLEIVPVLPLDIPADTRY GSIRAELESLGQTIGSNDLLIAAHAYALDLTLVTDNIREFSRVRGLSLENWLER SEQ ID NO : 133 >gi|13471640|ref|NP_103206. 11 NtrR protein [Mesorhizobium loti] MRFMLDTNIISDMIRNPAGKAAGAMVREGDAAVCTSIWASELRYGCARKGSTKLLKKVED LLAEIPVLPLDVPVDAEYG ALRAELEAVGQPIGYNDLFIAAHACVLGTTLVTANIGEFTRIRKLKVENWLE SEQ ID NO : 134 >gi|23014091|ref|ZP_00053928. 11 hypothetical protein [Magnetospirillum magnetotacticum] MRYLLDTNILSDMLRHPQGPAAHRLAEVGEDHVCTSIICAGELRFGAIRKGSARLAALVA ALLDTIEVLPLEDPTSSVYG EIRTALEQEGRPIGGNDLWIAAHALALGVTLVTANEGEFRRVDGLRVENWGR SEQ ID NO : 135 >gi|22982012|ref|ZP_00027339. 11 hypothetical protein [Burkholderia fungorum] MIRNPFGQVAARIEQIDPRAICTSVWAAELRYGCAKKGSAKLLARVESLLATIPVLPLDV PADTEYGGIRAELEAAGQP IGANDLLIGAHAYALGLTLVTDNTKEFSRIRGLTIENWLDR SEQ ID NO : 136 >gi) 23006606refZP00048848. l) hypothetical protein [Magnetospirillum magnetotacticum] MRYLLDTNILSALVRSPRGPVAERIGRVGEARLYTNVIVAAELRYGATRKGSERLSRQIE AVLGAIPIEAWREPFDRAYA ELRSGLERAGTPIGANDLLIGAQALADGSVLVTDNTREFERITGLTIENWLRP SEQ ID NO : 137 >gi|22997450|ref|ZP_00041681. 1| hypothetical protein [Xylella fastidiosa Ann-1] MAAELRYGCTKNGSVKLLSRVQDILKTLPILPLDIPVDTTYGSIRAELEAAGQLIGANDL LIAAHAYVLGLTLVTDNTRE FSRIRGLDVQNWLER SEQ ID NO : 138 >gi|30248513|ref|NP_840583. 11 PIN (PilT N terminus) domain [Nitrosomonas europaea ATCC 19718] MISPRYLLDTNILSDLVRYPQGVIARRIEEVGEAAVCTSIIVAAELRFGAARRNSLRLTR QVEAILAAIEVLPLDTPVDR AYAQLRWVLEQSGQVIGPNDMLITAQAMASQCVLITANLDKFSRVGELQVENWLVR SEQ ID NO : 139 >gi|16329604|ref|NP_440332. 1| virulence associated protein C [Synechocystis sp. PCC 6803] MKYLLDTNICIYLIKKKPFKVLAKFQTLEISDIGISSITVAELEYGVSKSQQQSKNRDAL MQFLMPLEIVEFNSGSGDRL WQH SEQ ID NO : 140 >gi|17228988|ref|NP_485536. 11 virulence associated protein C [Nostoc sp. PCC 7120] MSGEIALDTSVAIRFLNGDPDWSRVLALPEIFLSWWGELLFGAENSTRPLKNLPRYLEFM EVCTWPVEKRTAVIYA QTRSALKRKGRPIPMNDVWIAAHCLEHGWVLVTDNSDFDYVDGLVIEHW SEQ ID NO : 141 >gi|15922260|ref|NP_377929. 1| 133aa long hypothetical virulence-associated protein [Sulfolobus tokodaii] MGKMECKCLDSDILIDFLRGKEKAVKYIESVRGSSRIVTTVINVFELYYGALKYNKDVEK LDEFLQSVEILPFTVSEAKK AAEIEVDLENRGEVIGLKDVLISSIALNNNCTIVTGNVKHFERIQGVKVENWK SEQ ID NO : 142 >gi|16331532|ref|NP_442260. 1| virulence associated protein C [Synechocystis sp. PCC 6803] MQYPYLLDRNILSNLIRHPNGTIFFKIKEVGEANISTSIIVACELAFGAEKKQSKRLQER VNLILDLVPIAPMLAGMEKV YGKIRAILEHQGTPIGGNALLIASQAIYANLILVTDNTGEFKRMPGLSVENWL

SEQ ID NO : 143 >gi|30248306|ref|NP_840376. 1| PIN (PilT N terminus) domain [Nitrosomonas europaea ATCC 19718] MLILDSNTISYYFRGDPQWLRLQAQRPQDVAVPAIVEYELRYGLLRLPPEMAAPRLAALT TLLLPMQKLPFDSECADHA ARIRTTLEAAENPIGPHDTLIAATALRHGATLITRNVREFSRVPGLQWINWHEG SEQ ID NO : 144 >gi|32527189|gb|AAP85939. 1| putative plasmid maintenance protein [Ralstonia eutropha] MVSAVSWLLDTNIVSEAMRPRPEVAVTDNLARYEGELAIPAPVWHELRYGWLRMPDGQRK DAVGRFVQDWGTLPVLPYD AAAARIHAELRQSRERAGFTLPFVDGQIASVAIAHGLTLVTRNTKDFSELTGLRLANWFV P SEQ ID NO : 145 >gi|17232093|ref|NP_488641. 1| hysothetical protein [Nostoc sp. PCC 7120] MVKKLTQHQLETATGSWMHELLFGCLRLVESQKRRLLLEYINQIPLKMTILNYDLKAAQW HAQERARLSKMGKTPAFID GQIASIAYSNNLILVTNNVSDFESFNDLAVENWFVNSGEG SEQ ID NO : 146 >gi|15807096|ref|NP_295825. 1| plasmid stability protein, putative [Deinococcus radiodurans] MLALDTNILIALQKLEPAAFGHDRQALMTVPWIPSWRYEARRSLLAPQYARRLAQLDQLL SGHATLDFDQQAADIAAD IYHQLCTTGQLIDEADLMIAALSIQHGAALVTRNTSHFQRIPGLTLLDWL SEQ ID NO : 147 >gi|23464899|ref|NP_695502. 1 plasmid stability protein StbB [Bifidobacterium longum NCC2705] MIILDTNVISEIIKKQPDEHVANWLRNQDTSNLATTAITVAELLAGICRMPEGKRRKYTD TTVKLALMTLEDRTFAFDTQ AAADYAHILVEREHRGTPTSIQDAMIAAIACSWDAAIATRNIKDFEGTDVELINPWEFA SEQ ID NO : 148 >gi|20089859|ref|NP_615934. 1| Pin protein [Methanosarcina acetivorans str. C2A] MGRMKFFVDTSIFVDCLRKEVIPSSKSFLERIGDEYSGYTSSITVAELSVGAHLSRSQDA LEKTLELLNIVEVIDLDSRI AIDAGKIYADLIRSGKRIELNDCLIAATALSLGINRE SEQ ID NO : 149 >gi15892302 refJNP360016. 1 unknown [Rickettsia conorii] MGLIIDTAIIIALEREKVSTKQWSHYGQTYISPIVLTELLIGVYRVKNENKRIKCLAFIE YVKSLFTILPFGIEEVYTYA RITHDLYTQRITIGTHDMLIAATAITKGFLILTLNVKDFKRIQGLEVLTVSSKD SEQ ID NO : 150 >gi30249060 ref NP841130. 1j PIN (PilT N terminus) domain [Nitrosomonas europaea ATCC 19718] MIVLDTNVLSEILRPVPDTQVLVWLAAQPRSVLFTTTVTRAELFYGVRLLPDGQRQTALL DAIQSIFDQDLAGHVLNFDS TAADTYAKIAASRKAVGKPISQFDAMIAAMAKSKGASLATRNLKDFVDCGIDLVNPWSTS YLK SEQ ID NO : 151 >gi|15669i04|ref|NP_247909. 1| conserved hypothetical protein [Methanococcus jannaschii] MKILKKLKKKLEKEESKILVDTSVLIDYFKKRRLEELGGEAISIITAVEFIRGISEHKQE QVLNIFKELFEIVYIDEEII IPFSKIYRQLKKRGMLIDDADLYIACTAIIKNYPLWTKNKKHFERLKEFGLKIYDK SEQ ID NO : 152 >gi|13474235|ref|NP_105803. 1| plasmid stabilization protein [Mesorhizobium loti] MIFVDTNVISESLKKTPDPAVLAWLVRNDAELALPTVTIAEIAFGIQKIRPDERADRLEQ GLSRWRHRFADRIFGLTEEA ALAYGAIMGAATRQGPGMSAPDGMIAAIARVNGGRLATRNLNDFGTTSLDLISPWNF SEQ ID NO : 153 >gi|17230971|ref|NP_487519. 1| similar to nitrogen regulation protein NtrR [Nostoc sp. PCC 7120] MYLLDTNHCSRIIFGDSNLIQQLQLNSEAGIATSWWCGELLYMAAKSDRSVANLQQVRVF LDTIDIYPVNFSISEVYGN LKGKLVNAFGPKEKAQRRNFNLQALGFGDNDLWIAATAIHYNLTWSTDNDFRRIQQVETL LLESWLAS SEQ ID NO : 154 >gi|16119246|ref|NP_395952. 1| AGR_pAT_21p [Agrobacterium tumefaciens] MIFLDTNVMSETFKKAPDSAVIAWLVRHDAELALPTVAVAEIAFGIQKIRPDQRADRLEE GLVSWRRRFSDKMFAFTEEA ALAYGDIMGDAARQGRGMSAPDGMIAAITRINGGRLATRNLKDFETTGLELISPWQF SEQ ID NO : 155 >gi|5103261, Length 85 mhttrlkrvg gsvmltvppa llnalslgtd nevgmvidng rlivepyrrp qyslaellaq cdpnaeisae erewlda- pat gqeei Kid/PemK toxin of R1/R100 :

SEQ ID NO : 156 >gi|5103262, Length 133 mlkyqlknen gwmhrrlvrr ksdmergeiw lvsldptagh eqqgtrpvli vtpaafnrvt rlpwvpvts ggnfart- agf avsldgvgir ttgwrcdqp rtidmkargg krlervpeti mnevlgrlst ilt SEQ ID NO : 157 MazE/ChpAI/ChpR of E. coli K-12 >gi|16130690, Length 82 mihssvkrwg nspavripat lmqalnlnid devkidlvdg kliiepvrke pvftlaelvn ditpenlhen idwgepkdke vw SEQ ID NO : 158 MazE/ChpAK/ChpK of E. coli K-K12 >gi|16130689, Length 115 mvsryvpdmg dliwvdfdpt kgseqaghrp awlspfmyn nktgmftclc vpcttqskgy pfewlsgqe rdgvaladqv ksiawrarga tkkgtvapee lqlikaftki nvlig SEQ ID NO : 159 ChpBI/ChpS antitoxin of E. coli K-12 >gi|16132046, Length 85 mqmritikrw gnsagmvipn ivmkelnlqp gqsveaqvsn nqliltpisr rysldellaq cdmnaaelse qdvwgkstpa gdeiw SEQ ID NO : 160 ChpBK/ChpB toxin of E. coli K-12 >gi|16132047, Length 113 mvkkseferg divlvgfdpa sgheqqgagrp alvlsvqafn qlgmtlvapi tqggnfaryag fsvplhceeg dvhgwlvnq vrmmdlharla kriglaadev veeallrlqa we SEQ ID NO : 161 >giI15609128IrefINP_216507. 11 hypothetical protein Rvl991c [Mycobacterium tuberculo- sis H37Rv] MVISRAEIYWADLGPPSGSQPAKRRPVLVIQSDPYNASRLATVIAAVITSNTALAAMPGN VFLPATTTRLPRDSWNVTA IVTLNKTDLTDRVGEVPASLMHEVDRGLRRVLDL SEQ ID NO : 162 >gi|15609938|ref|NP_217317. 1 {hypothetical protein Rv2801c [Mycobacterium tuberculo- sis H37Rv] MMRRGEIWQVDLDPARGSEANNQRPAWWSNDRANATATRLGRGVITWPVTSNIAKVYPFQ VLLSATTTGLQVDCKAQA EQIRSIATERLLRPIGRVSAAELAQLDEALKLHLDLWS SEQ ID NO : 163 >gi1156130851refINP-241388. 11 BH0522-unknown conserved protein [Bacillus halodurans] MIVKRGDVYFADLSPWGSEQGGVRPVLVIQNDIGNRFSPTVIVAAITAQIQKAKLPTHVE INAKRYGFDRDSVILLEQI RTIDKQRLTDKITHLDDDMMSKVNDALLISLGLIDF SEQ ID NO : 164 >gi|15616283|ref|NP_244588. 11 ppGpp-regulated growth inhibitor (ChpA/MazF) [Bacillus halodurans] MPVPDRGNLVYVDFNPQSGHDQAGTRPAIVLSPKLFNKNTGFAWCPITRQQKGYPFEIEI PPGLPIEGVILTDQVKSLD WRARNFHIKGQAPEETVTDCLQLIHTFLS SEQ ID NO : 165 >gi|15676808|ref|NP_273953. 1| pemK protein [Neisseria meningitidis MC58] MYIPDKGDIFHLNFDPSSGKEIKGGRFALALSPKAFNRATGLVFACPISQGNAAAARSSG MISTLLGAGTETQGNVHCHQ LKSLDWQIRKASFKETVPDYVLDDVLARIGAVLFD SEQ ID NO : 166 >gi|15803303|ref|NP_289336. 1| probable growth inhibitor, PemK-like, autoregulated [Escherichia coli 0157 : H7 EDL933] MVSRYVPDMGDLIWVDFDPTKGSEQAGHRPAWLSPFMYNNKTGMCLCVPCTTQSKGYPFE WLSGQERDGVALADQVKS IAWRARGATKKGTVAPEELQLIKAKINVLIG SEQ ID NO : 167 >gi|15804816|ref|NP_290857. 1| probable growth inhibitor, PemK-like, autoregulated [Escherichia coli 0157 : H7 EDL933] MVKKSEFERGDIVLVGFDPASGHEQQGAGRPALVLSVQAFNQLGMTLVAPITQGGNFARY AGFSVPLHCEEGDVHGWLV NQVRMMDLRARLAKRIGLAADEWEEALLRLQAWE SEQ ID NO : 168 >gi|15805444|ref|NP_294140. 1| ppGpp-regulated growth inhibitor ChpA/MazF, putative [Deinococcus radiodurans] MVSDYVPDAGHLVWLNFTPQAGHEQGGRRPALVLSPAAYNGVTGLMQACPVTSRAKGYPF EVTLPAHLGVSGWLADHCR

SLDWRSRRAEQLAEAPADVLAEVRGKLGSLLGMSEKA SEQ ID NO : 169 >gi|15805689|ref|NP_294385. 1| conserved hypothetical protein [Deinococcus radi- odurans] MAVGLIRRGDIFLTHFGPARAGEPDFKRPAWITNNVANAKADAVTVIPLTSNLETLYDFQ LLLPTERTGLNLDSKAQTE LISCIAISRIGKHLGQVPADLMAELDARIRLHLAL SEQ ID NO : 170 >gi|15832896|ref|NP_311669. 1| PemK-like cell growth regulatory protein ChpA [Es- cherichia coli 0157 : H7] MVSRYVPDMGDLIWVDFDPTKGSEQAGHRPAWLSPFMYNNKTGMCLCVPCTTQSKGYPFE WLSGQERDGVALADQVKS IAWRARGATKKGTVAPEELQLIKAKINVLIG SEQ ID NO : 171 >gi|15834457|ref|NP_313230. 11 probable growth inhibitor [Escherichia coli 0157 : H7] MVKKSEFERGDIVLVGFDPASGHEQQGAGRPALVLSVQAFNQLGMTLVAPITQGGNFARY AGFSVPLHCEEGDVHGWLV NQVRMMDLRARLAKRIGLAADEWEEALLRLQAWE SEQ ID NO : 172 >gi|15841472|ref|NP_336509. 1| conserved hypothetical protein [Mycobacterium tubercu- losis CDC1551] MVISRAEIYWADLGPPSGSQPAKRRPVLVIQSDPYNASRLATVIAAVITSNTALAAMPGN VFLPATTTRLPRDSWNVTA IVTLNKTDLTDRVGEVPASLMHEVDRGLRRVLDL SEQ ID NO : 173 >gi|15842339|ref|NP 337376. 1| pemK protein [Mycobacterium tuberculosis CDC1551] MRRGEIWQVDLDPARGSEANNQRPAVWSNDRANATATRLGRGVITWPVTSNIAKVYPFQV LLSATTTGLQVDCKAQAE QIRSIATERLLRPIGRVSAAELAQLDEALKLHLDLWS SEQ ID NO : 174 >gi|15888280|ref|NP_353961. 1| AGR_C_1712p [Agrobacterium tumefaciens] MMVRNQIPKRGDVYLVDLNPWGSEIKDEHRCWITPREINAVGLCLWPVTTGGMFTRKAGL AVNISGHKTTGVALCNQ VRSMDIVARVAQKKAKYIETLDDATIDEIAGRVISMIDPA SEQ ID NO : 175 >gi|15893379|ref|NP_346728. 11 PemK family of DNA-binding proteins [Clostridium aceto- butylicum] MKNTRIKDMRDDELQAYIKETKKEIEQQLKLYVKLNNDKLSNNGQIQNLKKKAYNLKEVY EYIKWANDKIAINNNVESSY GTIPKRGEIWTCQLGENIGSEENKIRPAIIIQNDTGNEKGPTTIIVPISNRPKKISTHIE LRPGDYKLVHGEVNKITGTI LCEQIKWSKARLGRHVATLNSDFVNKILNSKLKISIKV SEQ ID NO : 176 >gi|15893785|ref|NP 347134. 1| PemK family of DNA-binding proteins [Clostridium aceto- butylicum] MTIWKRGDIFYADLSPWGSEQGGIRPVIIIQNDMGNKYSPTVIVAAITSQINKAKLPTHV EISSEDYGLNKDSWLLE QIRTLDKRRLKEKIGHMTDMDMKKVDEALLISIGLQNMFESV SEQ ID NO : 177 >gi|15925058|ref|NP_372592. 1| conserved hypothetical protein [Staphylococcus aureus subsp. aureus Mu50] MIRRGDVYLADLSPVQGSEQGGVRPWIIQNDTGNKYSPTVIVAAITGRINKAKIPTHVEI EKKKYKLDKDSVILLEQIR TLDKKRLKEKLTYLSDDKMKEVDNALMISLGLNAVAHQKN SEQ ID NO : 178 >gi|15927643|ref|NP_375176. 11 conserved hypothetical protein [Staphylococcus aureus subsp. aureus N315] MIRRGDVYLADLSPVQGSEQGGVRPWIIQNDTGNKYSPTVIVAAITGRINKAKIPTHVEI EKKKYKLDKDSVILLEQIR TLDKKRLKEKLTYLSDDKMKEVDNALMISLGLNAVAHQKN SEQ ID NO : 179 >gi|16077533|ref|NP_388347. 1| similar to hypothetical proteins [Bacillus subtilis] MIVKRGDVYFADLSPWGSEQGGVRPVLVIQNDIGNRFSPTAIVAAITAQIQKAKLPTHVE IDAKRYGFERDSVILLEQI RTIDKQRLTDKITHLDDEMMDKVDEALQISLALIDF SEQ ID NO : 180 >gi|16130689|ref|NP_417262. 1| probable growth inhibitor, PemK-like, autoregulated [Escherichia coli K12] MVSRYVPDMGDLIWVDFDPTKGSEQAGHRPAWLSPFMYNNKTGMCLCVPCTTQSKGYPFE WLSGQERDGVALADQVKS IAWRARGATKKGTVAPEELQLIKAKINVLIG SEQ ID NO : 181

>gi|16132047|ref|NP_418646-1l probable growth inhibitor, PemK-like, autoregulated [Escherichia coli K12] MVKKSEFERGDIVLVGFDPASGHEQQGAGRPALVLSVQAFNQLGMTLVAPITQGGNFARY AGFSVPLHCEEGDVHGWLV NQVRMMDLHARLAKRIGLAADEWEEALLRLQAWE SEQ ID NO : 182 >gi|16799960|ref|NP_470228. 1| similar to B. subtilis YdcE protein [Listeria innocua] MMVKRGDVYYADLSPWGSEQGGIRPVLIIQNDIGNRFSPTVIVAAITAKIQKAKLPTHVE ATRKDGFERDSVILLEQIR TIDKQRLTDKITHLDEELMAKVNQALEVSLGWEF SEQ ID NO : 183 >gi|16802929|ref|NP_464414. 1| similar to B. subtilis YdcE protein [Listeria monocyto- genes EGD-e] MMVKRGDVYYADLSPWGSEQGGIRPVLIIQNDIGNRFSPTVIVAAITAKIQKAKLPTHVE ATRKDGFEKDSVILLEQIR TIDKQRLTDKITHLDEDLMAKVNKALEVSLGWEF SEQ ID NO : 184 >gi|17230703|ref|NP_487251. 1| cell growth regulatory protein [Nostoc sp. PCC 7120] MKPPYFPNRGDIVKLEFGSAQQFTAESIQRVFTLRNSGMSFDDIAITLNNELQQQGREQT GYRPVLVISPIKYNQMASLV LACPITTNAKGLRFEVPLIEGMKTKGWLADQIKTLDWKARKVKFVESVTEDLIEEVQAKL ETLIL SEQ ID NO : 185 >gi|17232413|ref|NP_488961. 11 hypothetical protein [Nostoc sp. PCC 7120] MSIERGQIYFVNLNPVHGREQAGARPVLVLSTDAINQLPLVITVVVGTKGTNIKRDYPTN IRVSPSDSGLVIETVFLCFQ IRSLDPNRFPTDPSGKLSASKMLEVETAVRYCLGL SEQ ID NO : 186 >gil7934848refNP531638. 1 PemK protein [Agrobacterium tumefaciens str. C58 (U. Washington)] MVRNQIPKRGDVYLVDLNPWGSEIKDEHRCWITPREINAVGLCLWPVTTGGMFTRKAGLA VNISGHKTTGVALCNQV RSMDIVARVAQKKAKYIETLDDATIDEIAGRVISMIDPA SEQ ID NO : 187 >gi|18309277|ref|NP_561211. 1| conserved hypothetical protein [Clostridium perfrin- gens] MASLNVKRGDIFYADLSPWGSEQGGIRPVIIIQNDIGNRYSPTVIVAAITSQINKAKLPT HVEISSEEYGLNRDSWLL EQIRTLDKKRLKEKIGHMTEDDMKKVNKSLLISLNLQ SEQ ID NO : 188 >gi|20808550|ref|NP 623721. 1| Growth inhibitor [Thermoanaerobacter tengcongensis] MIMVVKRGDLFYADLSPVIGSEQGGIRPVLIIQNDIGNKYSPTVIVAAITSQINKAKLPT HVEINGAEYGLQKDSVILLE QIRTIDKKRLREKIGHLDQEMMEKVNEALQISLGLIDF SEQ ID NO : 189 >gi|21283721|ref|NP_646809. 1| conserved hypothetical protein [Staphylococcus aureus subsp. aureus MW2] MIRRGDVYLADLSPVQGSEQGGVRPWIIQNDTGNKYSPTVIVAAITGRINKAKIPTHVEI EKKKYKLDKDSVILLEQIR TLDKKRLKEKLTYLSDDKMKEVDNALMISLGLNAVAHQKN SEQ ID NO : 190 >gi|23098078|ref|NP_691544. 1| hypothetical protein [Oceanobacillus iheyensis HTE831] MIVQRGEVYFADLSPWGSEQGGVRPVLILQNDIGNRFSPTVIVAAITAQIQKAKLPTHVE IDAKRYGFDRNSVILLEQI RTLDKQRLTDKITKLDKEMMIKINQALEISLGLKDVYGG SEQ ID NO : 191 >gi|24114678|ref|NP_709188. 1| PemK protein [Shigella flexneri 2a str. 301] MVKARTPHRGEIWYFNPDPVAGHELQGPHYCIVVTDKKLNNVLKVAMCCPISTGANAARS TGVTVNVLPRDTQTGNLHGV VLCHQLKAVDLIARGAKFHTVADEKLISEVISKLVNLIDPQ SEQ ID NO : 192 >gi|24214481|ref|NP_711962. 11 probable ppGpp-regulated growth inhibitor ChpA/MazF [Leptospira interrogans serovar lai str. 56601] MVKNRNYTPEKGDIVWLNFTPQAGHEQKGRRPALVLSPKEYNSKTGLAIFCPITSKIKGY PFEVLIKSKKIDGVILSDQV KNLDWTIREAEFIESINKVSLKEVLDNIKLLIF SEQ ID NO : 193 >gi|24215543|ref|NP_713024. 11 chpK [Leptospira interrogans serovar lai str. 56601] MIRGEIWWVDLGIPFGSEPGFKRPVLIIQDDSFNQSNINTIVSIAITSNLNLSEAPGNVF ISKKDSSLSKDSVINVSQIV TLDKERFLNKAGKLKSNKLGEVEIGLKLVTGLD SEQ ID NO : 194 >gi|24378687|ref|NP_720642. 11 putative ppGpp-regulated growth inhibitor [Streptococ- cus mutans UA159]

MVTIKQGSIIKINLDPKQGHEQKGYRPYICLNHSIVTKYSNIGIFAPISNTKRDYPFYVS LEGTESTGKVLLDQLVTIDF NARDYRYVEDIQEDLLDELLARVKVLFEKG SEQ ID NO : 195 >gi|26987507|ref|NP_742932. 1| transcriptional regulator, PemK family [Pseudomonas putida KT2440] MKRLKFARGDIVRVNLDPTVGREQQGSGRPALVLTPAAFNASGLAVIIPITQGGDFARHA GFAVTLSGAGTQTQGVMLCN QVRTVDLEARFAKRIESVPEAVILDALARVQTLFD SEQ ID NO : 196 >gi|27468590|ref|NP_765227. 1| conserved hypothetical protein [Staphylococcus epider- midis ATCC 12228] MIRRGDVYLADLSPVQGSEQGGVRPWIIQNDTGNKYSPTVIVAAITGRINKAKIPTHVEI EKKKYKLDKDSVILLEQIR TLDKKRLKEKLTFLSESKMIEVDNALDISLGLNNFDHHKS SEQ ID NO : 197 >gi28377410ref) NP784302. 1 unknown [Lactobacillus plantarum WCFS1] MAAADIKRGDIFYADLSPWGSEQGGMRPVLIVQNNVGNHYSPTVIVAAITAKVQKAKMPT HVNINAAHTGIEKNSWLL EQIRTIDKQRLKDRVTHLDDQTMRRVDNALQISIGLADRTRRRPQRTFQS SEQ ID NO : 198 >gi|28379346|ref|NP_786238. 1| cell growth regulatory protein [Lactobacillus plantarum WCFS1] MTYLPKQKDIIWIDFDPQRGREIKKRRPAWLSSNLYTQNTGFVIVSPITSTMRDLPGYFS LNGYNTHGQIAAAQIYSFD ATPRAGRSITYIETMRSADFYHVAQTVYYNFDFPF SEQ ID NO : 199 >gi|29375414|ref|NP_814568. 1| transcriptional regulator, PemK family [Enterococcus faecalis V583] MIKRGEVFYANLSPVVGSEQGGIRPVLIIQNNKGNLFSPTLIVAPITRNVSKRLQPTQVL IEIPHNECRTPSLILLEQIR TLDKERMLHKVCQLSREEMEQVNQALKVSVGIR SEQ ID NO : 200 >gi|29375438|ref|NP_814592. 11 transcriptional regulator, PemK family [Enterococcus faecalis V583] MVKRGDIYFADLSPWGSEQGGVRPVLWQNNLGNHFSPTIIVAAITAKMAKPKLPTHIGIN SDETGIEKDSVILLEQIR TIDKGRLKEKVCHLRLDIMEEVDRALGISVGLSSDSAPAKANSAT SEQ ID NO : 201 >gi|30018503|ref|NP_830134. 1| pEMK-like protein [Bacillus cereus ATCC 14579] MIVKRGDVYFADLSPWGSEQGGVRPVLVIQNDIGNRFSPTVIVAAITAQIQKAKLPTHVE IDAKKYGFERDSVILLEQI RTIDKQRLTDKITHLDEVMMIRVDEALQISLGLIDF SEQ ID NO : 202 >gi|30248977|ref|NP_841047. 11 PemK-like protein [Nitrosomonas europaea ATCC 19718] MTYLPNRGDIVHLDFDPSSGREIKGPHFGLILSGKLFNQRGLAMICPISQGAAAAARTYG TWTLMGAGTDTQGAVHCHQ LKSLDWQVRNVRFKESVPQHILDEVLARVEAILFE SEQ ID NO : 203 >gi|30249167|ref|NP_841237. 1| PemK-like protein [Nitrosomonas europaea ATCC 19718] MTDFKQRDIYWIDLEPTKGAETRKLRPCVIIQSDLVNVQSRTVIVAPLLLQHKPWPFAVN LEPTEKNGLDKDRHINLKQL RAVDISRIGKKQGRLENRYKDPIKAALMIIFDL SEQ ID NO : 204 >gi|30249548|ref|NP_841618. 1| PemK-like protein [Nitrosomonas europaea ATCC 19718] MAKILRGEIRWANLNPTVGREQSGERPILVLSQDIFNERSGTVIAMALTSQEQRAGFPLT YEILKSSLPKRSWVKISQIR TLSTERIGKKIGAIAPEELAQIVEGLNEIIGS SEQ ID NO : 205 >gi|30260430|ref|NP_842807. 1} transcriptional regulator, PemK family [Bacillus an- thracis str. Ames] MIVKRGDVYFADLSPWGSEQGGVRPVLVIQNDIGNRFSPTVIVAAITAQIQKAKLPTHVE IDAKKYGFERDSVILLEQI RTIDKQRLTDKITHLDEVMMIRVDEALQISLGLIDF SEQ ID NO : 206 ParD of plasmid RK2, antitoxin >gi|420754, Length 83 msrltidmtd qqhqslkala alqgktikqy alerlfpgda dadqawqelk tmlgnrindg lagkvstksv geildeelsg dra SEQ ID NO : 207 ParE of plasmid RK2, toxin

>gi|420755, Length 103 ltayiltaea eadlrgiiry trrewgaaqv rryiakleqg iarlaagegp fkdmselfpa lrmarcehhy vfclpragep alwailher mdlmtrladr lkg ParE core sequences : SEQ ID NO : 208 >gi|1560iO76lref|NP_232707. 1| hypothetical protein [Vibrio cholerae] MSVYLNMQNKQYKLSQLAQEHLLKIKHYTIENFAEAQWQKYKSTLLSGFQTLADNPGLGK SCEDIYQNGFYFPVGKHMAY YTKEANFILIVAVLGQSQLPQKHLKQSRFVS SEQ ID NO : 209 >gi] 15601123) refNP232754. 1 plasmid stabilization element ParE, putative [Vibrio cholerae] MKPFNLTVAAKADLRDIALFTQRRWGKEQRNVYLKQFDDSFWLLAENPDIGKSCDEIREG YRKFPQGSHVIFYQQTGSQQ IRVIRILHKSMDVNPIFGA SEQ ID NO : 210 >gi|15601148|ref|NP_232779. 11 conserved hypothetical protein [Vibrio cholerae] MSVYLNMQNKQYKLSQLAQEHLLKIKHYTIENFAEAQWQKYKSTLLSGFQTLADNPGLGK SCEDIYQNGFYFPVGKHMAY YTKEANFILIVAVLGQSQLPQKHLKQSRFVS SEQ ID NO : 211 >gi|15609096lref|NP_216475. 1| hypothetical protein Rv1959c [Mycobacterium tuberculo- sis H37Rv] MSSRYLLSPAAQAHLEEIWDCTYDRWGVDQAEQYLRELQHAIDRAAANPRIGRACDEIRP GYRKLSAGSHTLFYRVTGEG TIDWRVLHQRMDVDRNL SEQ ID NO : 212 >gi|15838626|ref|NP_299314. 1| plasmid stabilization protein [Xylella fastidiosa 9a5c] MTGYVLTEAAESDLRGIVRYTRKQWGNAQVRHYIATLERGIASLAEGRGAFNDMSSLFPA LRMGRYEHHYVFCLPREEAP ALIVAIFHERMDLMTRLADRLK SEQ ID NO : 213 >gi|15841429|ref|NP_336466. 1| plasmid stabilization protein ParE [Mycobacterium tu- berculosis CDC1551] MSSRYLLSPAAQAHLEEIWDCTYDRWGVDQAEQYLRELQHAIDRAAANPRIGRACDEIRP GYRKLSAGSHTLFYRVTGEG TIDWRVLHQRMDVDRNL SEQ ID NO : 214 >gi|15888835|ref|NP 354516. 1| AGR_C_2785p [Agrobacterium tumefaciens] MSCVNNYRLSTQAENEILDIFLYGIERFGLNQARLYKDGMESCFQLLGNNPRMGRSATIV GEGIRRHEHGSHVIFYETDG SGVLILTIVHGRSIRRLKL SEQ ID NO : 215 >gi|16125126|ref|NP_419690. 11 conserved hypothetical protein [Caulobacter crescentus CB15] MKPYRLSRRAKADLDDIWTYSEQRWGVEQAADYARELQATIEMIAEHPGMGQPDENLRAG YRRCASGSHWFYRVGVRVE IIRVLHQSMNARAHLG SEQ ID NO : 216 >gi|27365828|ref|NP_761356. 11 Plasmid stabilization element ParE [Vibrio vulnificus CMCP6] MRPFQLTNKAKSDLRDIALFTSRRWGREQRNIYLKQFDDSFWLLAENPDIGKACDEIRDG YRKFPQGSHVIFYRQIGSQN IEIIRILHKSMDVNPIFGA SEQ ID NO : 217 >gi|30248281|ref|NP_840351. 1| putative plasmid stabilization element ParE [Nitrosomo- nas europaea ATCC 19718] MGSFILRQKAMDDLLSIGRYTRKEWGKTQQIRYLTQLDRAFHELADKPGLGRACDDIREG YFKYGVGKHVIFYRHTGKDQ IEIIRILHGRMDIEQHL SEQ ID NO : 218 >gi|30249495|ref|NP_841565. 1| putative plasmid stabilization protein ParE [Nitrosomo- nas europaea ATCC 19718] MAEYRLSPAAQRDLDGIFNYTFQQWGAAQAVRYIDILEAACTELVETSSQGQDCSYIRPG YRRRHVERHITTE SEQ ID NO : 219 >gi|30250054|ref|NP_842124. 1| putative plasmid stabilization protein ParE [Nitrosomo- nas europaea ATCC 19718] MKHYLLSPEAKTDITNIRQYTTQQWGKTQADKYILRLRERMRWLADNPMLGRARDEIKEG YRSFSEGDHVIFYRMAGSAI EVIGIPHQNMDIEQNLSSGNLLLPDIADYEPEDG

SEQ ID NO : 220 HigA from plasmid Rtsl, antitoxin >gi|1262205, Length 104 mrqfkvshpg emiardledm gvsgrrfahn igvtpatvsr llagktaltp slsiriaaal gstpefwlrl qsnydlrqle nqidtsgivl ygesneqqqn aqeh SEQ ID NO : 221 HigB from plasmid Rtsl, toxin >gi|1262204, Length 92 miksfkhkgl kllfekgvts gvpaqdvdri ndrlqaidta teigelnrqi yklhplkgdr egywsitvra nwritfqfin gdayilnyed yh SEQ ID NO : 222 >gi|13471566|ref|NP_103132. 1| hypothetical protein [Mesorhizobium loti] MIVGFRDGWLRAFFVDDTRSRNIPSDLESRLFRKLQMIDDATVDQDLRVPPSNHFEKLRG NLEGFHSIRVNQQWRLIFRW DGGRGEASDIYLDDHSYK SEQ ID NO : 223 >gi|15601154|ref|NP_232785. 11 killer protein, putative [Vibrio cholerae] MCTVSLCVSLCLWMHNETVQVAMALEFKDKWLEQFYEDDKRHRLIPSSIENALFRKLEIL DAAQAESDLRIPPGNRFEHL EGNLKGWCSIRVNKQYRLIFQWVDGVALNTYLDPHKY SEQ ID NO : 224 >gi|15837323|ref|NP_298011. 1| proteic killer suppression protein [Xylella fastidiosa 9a5c] MYTDHLRYTIGFVIKSFRHKGIQQFFLEGSTAGIQTKHAAKLRIQLTALESAKHPKDMNA PGWKLHSLKGADLKGHWSIW VNGNYRLTFAFEGEDAILVDYQDYH SEQ ID NO : 225 >gi|15838310|ref|NP 298998. 1| hypothetical protein [Xylella fastidiosa 9a5c] MEVKFEDPSLERLEANQKYTAGLVKVFHRRIQFIRASPDERAFYAMKSLHYEKLKDDPDN LYSMHLNDQWHLIMYLKAKE DDTRNLWIVSIVDYH SEQ ID NO : 226 >gi|15964804|ref|NP_385157. 1| CONSERVED HYPOTHETICAL PROTEIN [Sinorhizobium meliloti] MIVGFRDDWLRTFFVDDVRSRNIPYDLEARLFRKLQMIDDAATDQDLRVPPSNHFEKLRG NLAGLHSIRVNQQWRLIFRW DGTRGEADGIYLDDHSYR SEQ ID NO : 227 >gi|15966812|ref|NP_387165. 11 CONSERVED HYPOTHETICAL PROTEIN [Sinorhizobium meliloti] MIQSFGNKETEAVFKRQRTRRFGAFQKPALVKLLMLHAATRIEDLRVPPGNRLEALKGDR AGQYSIRINQQWRICFRFEN GDAYDVEISDYH SEQ ID NO : 228 >gi|16273169|ref|NP_439406. 1| hypothetical protein [Haemophilus influenzae Rd] MFNLKREHFRDDYLYRFYQYGDTHSKIPSNLYKVLARKLDMISASENINDLRSPPANHLE LLEPKENKIYSIRVNKQYCL IFKYENNEVNNLYLDPHSYNL SEQ ID NO : 229 >gi|17230416|ref|NP_486964. 1| hypothetical protein [Nostoc sp. PCC 7120] MSPSDEYPKYKDKRTEKFALGERVKEFQSFERQAQKRLDIIDAAPNKEVLMQLPSNRFES LGGDRKGQYSIRINEQWRIC FNWPDDFLKPFNIEITDYH SEQ ID NO : 230 >gi|26247767|ref|NP_753807. 11 Hypothetical protein [Escherichia coli CFT073] MNFRHKGLRDLFLLGKTSGVIPTQVKRLRHRLAVIDAACCLADIDMPGYRLHPLSGDRDG IWAISVSGNWRITFEFVNGD AYILDYEDYH SEQ ID NO : 231 >gi|26988318|ref|NP_743743. 1| killer protein, putative [Pseudomonas putida KT2440] MIRSFSCADTEALFTTGKTRRGSDIKSVAERKLAMLDAATELRDLRSPPGNRLESLSGNR ADQHSIRVNDQWRLCFTWTE HGPVNVEIVDYH SEQ ID NO : 232 >gi27378123refNP_769652. 1 bs13012 [Bradyrhizobium japonicum] MIRTFRDKTTEAVFDGESPKGFPADLVKVARRKLRYLHAAGELGDLRAPPGNRLEALSGN RKGQHSIRINDQFRVCFIWT PQGPVEVEIVDYH SEQ ID NO : 233 >gi|28377333|ref|NP_784225. 11 plantaricin biosynthesis protein PlnX (putative) [Lac- tobacillus plantarum WCFS1] MPPTIQQLALRKLLMIDHAETINDLSLPPANHLEKLSHDRQGQYSIRINNQYRICFAIRN GNEFYDVEIVDYHHG

SEQ ID NO : 234 >gi|28867445|ref|NP_790064. 1| proteic killer protein, putative [Pseudomonas syringae pv. tomato str. DC3000] MIVSFKCVHTRYLFLQGKTRLWPSIKSVAERKLAMLDAATSILDLRSPPGNRLEALDGSR SGQYSVRINAPFRICFVWSI NGPEDVEIVDYH SEQ ID NO : 235 >gi|28867653|ref|NP_790272. 11 proteic killer protein, putative [Pseudomonas syringae pv. tomato str. DC3000] MIVSWRHKGLKAFFETGSSSGIRADHSKRLAHVLAVLNRARTPANVNMPGWRLHPLKGEL EGFWSITINANWRIIFRFFD TDVELVDYLDYH SEQ ID NO : 236 >gi|29654782|ref|NP_820474. 1| proteic killer protein, putative [Coxiella burnetii RSA 493] MLDVTRKTVILEVIIKSFKDKYTKYLYKGVSVSKWQAIRKQAERRLQILDSVTSLDDLRS LPSNRFESLRGNRKGQFSIR INKQWRICFKWINNEPTEVEIVDYH SEQ ID NO : 237 >gi|30248497|ref|NP 840567. 1| conserved hypothetical protein [Nitrosomonas europaea ATCC 19718] MGCMIQSFRCKSTQAMFEGECPQRFSAIQAVAERKLAQLEAAQTLDFLRSPPGNRLEKLA GDREGQWSIRINAQWRICFT WSDLDPADVEIVDYH SEQ ID NO : 238 >gi|30248506|ref|NP_840576. 1| conserved hypothetical protein [Nitrosomonas europaea ATCC 19718] MSFDANIATQYYILMTIKTFRCADPETLFKLGRVARFVNIERPALRKLKQLDLARCIEDI RVPPANRPEILKGDRAGQHS IRINDQWRVCFRWTGTDAEDVEIVDYH SEQ ID NO : 239 >gi|30249098|ref|NP_841168. 11 conserved hypothetical protein [Nitrosomonas europaea ATCC 19718] MIKTFATKETAALFANEKIRRLPPEILRVARRKMAQLHRVSSIEELRIPPGNRLEKLSGN RNEQWSIRINDQWRICFRFE AGDVFDVEITDYH SEQ ID NO : 240 >gi|30249284|ref|NP_841354. 11 proteic killer suppression protein [Nitrosomonas eu- ropaea ATCC 19718] MIRHFKHKGLQLFFETGDKSGIRPDHASRLARQLRQLNDAVNPREMNIPGWKLHPLSGDL SGYWSVMVNGNWRMIFVFDG EDVILVDYRDDH SEQ ID NO : 241 Phd from plasmid Pl, antitoxin >gi|1083979, Length 73 mqsinfrtar gnlsevlnnv eageeveitr rgrepavivs katfeaykka aldaefaslf dtldstnkel vnr SEQ ID NO : 242 Doc from plasmid PI, toxin >gi|1083978, Length 126 mrhispeeli alhdanisry gglpgmsdpg raeaiigrvq arvayeeitd lfevsatylv atarghifnd ankrtalnsa llflrrngvq vfdspeladl tvgaatgeis vssvadtlrr lygsae Doc core sequences : SEQ ID NO : 243 >gi|15601236|ref|NP_232867. 1| doc protein [Vibrio cholerae] MDIICFPFERVIEINAFILKTEPGMKGAVDIPKLQGALGRIDNAIVYEGLDDVFEIAAKY TACIAVSHALPDANKRTGLA VALEYLSLNDFELTQENDLLADAVRDLVIGIINETDFADILYAQYAKEQNSAL SEQ ID NO : 244 >gi|15676812|ref|NP_273957. 11 death-on-curing protein [Neisseria meningitidis MC58] MIDGELVALIHQTVLADEAGLKGRADMARLDGALSRIANWRQYENLEDIYEIAALYAQAI AKAHAFPDGNKRTALLTMLT YLDLQGISIAADQGLDDLIVSLAAGETDFKQLAETLRRLDKE SEQ ID NO : 245 >gi|16122086|ref|NP_405399. 11 conserved hypothetical protein [Yersinia pestis] MADIVEGIHYLSVEDFIYINRTLIEAQTPSEPIDVINHNNLCSSQARPSWKYYQQTDDMF ELSAALIESLIQNHAFANA

NKRTAMMAGYMFLLLNGYELTAPGDEIWMAEGMARKVYNCEDLENWLCYWSRPYDSRNLC DCEISSLWTATQVKIE SEQ ID NO : 246 >gill6l27593lreflNp-422l57. ll death on curing protein [Caulobacter crescentus CB15] MSGVGEPVWVRIEALKVLHERSLALHGGPSGVRDEGLLESALERPKNRFHYEGVDDWELA ATYAVAVSSNHPFVDGNKR AAFHAMTLFLRLNGLRLVADQADAARTIFKLAAGELDIPALTDWLRTRVA SEQ ID NO : 247 >gi|16759893|ref|NP_455510. 11 putative bacteriophage protein [Salmonella enterica subsp. enterica serovar Typhi] MAIEYVEGVNYLSIEDIVYINRSLIEIQTPNEPIGVLNPNNLSSSQSRPSTIRYYEQTDD MFRLSAVLIESLIQNHPFAN ANKRTAMMAGYVFLLLNGYELTAPSDEVVTIAEGLARKDYAVDDLENWLCHWSREYDSRT LCETGGNMIQALVATSRYIR IKSNE SEQ ID NO : 248 >gi|16766844|ref|NP_462459. 11 homology to death-on-curing protein of phage P1 [Sal- monella typhimurium LT2] MTLQLISAEEIIQFHDRLLRVTPGVTGMPDPGRAEALMYRVLKQIEYEGVTDVWLLAAMH LLAISRGHIFNDGNKRTALF ITLLFLKRNGISLAANPDFVDMTVDAAAGRLTLEQIAVRLRA SEQ ID NO : 249 >gi|17987659|ref|NP_540293. 11 DEATH ON CURING PROTEIN [Brucella melitensis] MIDFHSRVFIEALHQEQLRLHGGATGIRDSSLLDSALARAQHKEAYGNPDIFDLAAAYLF GILKNHPFIDGNKRTGLAAA DLFLYFNGYSLEAEQEDVIQLVLMVTTSEIDETGAAAFFRDHAWINED SEQ ID NO : 250 >gi|21241948|ref|NP_641530. 1| death-on-curing protein [Xanthomonas axonopodis pv. citri str. 306] MNTRMLVWVTHALALAIHERQLSEHGGASGVRDEALLDSALARPQQLFSYGDPPPDLVGL TASLAYGLARNHPFVDGNKR TAHVCYRVFLLLNGAELIASQEEKYVAMMRLADGAWSEATFAQWLRPRVRLRADTHVHEP QGHYG SEQ ID NO : 251 >gi|21673172|ref|NP 661237. 1| Doc protein [Chlorobium tepidum TLS] MRFLDLHEVLHIHRDQITRYGGTLGVRDMGLLTSAIAMPTAMFKGDFLHTDIYEMAAAYL FHLVRNHPFLDGNKRVGAVS AIVFLALNGYDFEAPENDLVEMVYGVARSEFEKSDVALFMRRWSVKW SEQ ID NO : 252 >gi|22126357|ref|NP_669780. 1| hypothetical [Yersinia pestis KIM] MADIVEGIHYLSVEDFIYINRTLIEAQTPSEPIDVINHNNLCSSQARPSWKYYQQTDDMF ELSAALIESLIQNHAFANA NKRTAMMAGYMFLLLNGYELTAPGDEIWMAEGMARKVYNCEDLENWLCYWSRPYDSRNLC DCEISSLWTATQVKIE SEQ ID NO : 253 >gi|23501446|ref|NP_697573. 1| death-on-curing family protein [Brucella suis 1330] MIDFHSRVFIEALHQEQLRLHGGATGIRDSSLLDSALARAQHKEAYGNPDIFDLAAAYLF GILKNHPFIDGNKRTGLAAA DLFLYFNGYSLEAEQEDVIQLVLMVTTSEIDETGAAAFFRDHAWINDD SEQ ID NO : 254 >gi|28211562|ref|NP_782506. 11 death on curing protein [Clostridium tetani E88] MKHLSKEQMMYLHSMAVKKTGGLDGIRDEGLLDSALNSPFQSFAGEELYPSIQAKAARLG FSIIKNHPFLDGNKRIGMLA MMVFLEINGIQLECSDEDIVDIGLGIASGKYEDDYIIDWIISCSNNS SEQ ID NO : 255 >gi|29142335|ref|NP_805677. 11 putative bacteriophage protein [Salmonella enterica subsp. enterica serovar Typhi Ty2] MAIEYVEGVNYLSIEDIVYINRSLIEIQTPNEPIGVLNPNNLSSSQSRPSTIRYYEQTDD MFRLSAVLIESLIQNHPFAN ANKRTAMMAGYVFLLLNGYELTAPSDEWTIAEGLARKDYAVDDLENWLCHWSREYDSRTL CETGGNMIQALVATSRYIR IKSNE SEQ ID NO : 256 >gi|30249247|ref|NP_841317. 11 putative death on curing protein [Nitrosomonas europaea ATCC 19718] MTTPVWINEQDVLAIHERLIFLHGGASGIRDRNLLKSALARPLNFSVYDQQSDIFLLAAT YTSGILQNHPFVDGNKRTGF VIGVLFLELNGYKFIANEEDSAQAIISLAEGSLDELGFRLFIEHNSIAT SEQ ID NO : 257 >gi|30250372|ref|NP_842442. 11 putative death on curing protein [Nitrosomonas europaea ATCC 19718] MIEPIWIDEQVALAIHERLISLHSGASGVRDKELLKSALARPLNLLAYDQQADVIHLAAA YTAGILQNHPFVDRNKRTGF WGVLFLELNGYRFTAAEEDSAQAVIALAAGSLDEARFKLFLADNSIPV SEQ ID NO : 258 CcdA of plasmid F, antitoxin >gi|141247, Length 72

mkqritvtvd sdsyqllkay dvnisglvst tmqnearrlr aerwkaenqe gmaevarfie mngsfadenr dw SEQ ID NO : 259 CcdB of plasmid F, toxin >gi|141246, Length 101 mqfkvytykr esryrlfvdv qsdiidtpgr rmviplasar llsdkvsrel ypwhigdes wrmmttdmas vpvsvigeev adlshrendi knainlmfwg i SEQ ID NO : 260 >gi|15799733|ref|NP_285745. 1| putative toxin of gyrase inhibiting toxin-antitoxin system [Escherichia coli 0157 : H7 EDL933] MQFTVYRSRSRNAAFPFVIDVTSDIIGVINRRIVIPLTPIERFSRIRPPERLNPILLLVD GKEYVLMTHETATVPVNALG TKFCDASAHRTLIKGALDFMLDGI SEQ ID NO : 261 >gi|15829307|ref|NP_308080. 1| CcdB-like protein [Escherichia coli 0157 : H7] MQFTVYRSRSRNAAFPFVIDVTSDIIGVINRRIVIPLTPIERFSRIRPPERLNPILLLVD GKEYVLMTHETATVPVNALG TKFCDASAHRTLIKGALDFMLDGI SEQ ID NO : 262 >gi26245973refINP 752012. 1 Putative toxin of gyrase inhibiting toxin-antitoxin system [Escherichia coli CFT073] MQFTVYRSRGRNAAFPFVIDVTSDIIGEINRRIVIPLTPIERFSRIRPPERLNPILLLVD GKEYVLMTHETATVPVNALG TKFCDASAHRTLIKGALDFMLDGI SEQ ID NO : 263 >gi|30249069|ref|NP_841139. 1| putative CcdB-like protein [Nitrosomonas europaea ATCC 19718] MARFDVYVNPGSHAATTPYLLDVQSDLLDVLDSCMVIPLRSLEHFPKVKLPGRLTPWTIK GQDFLLETPKMGAIPRRLL TMPVLSLRDMQPEITSALDFLFHGY