Supplementary Table 2. Evaluation of Phenotypes with their significantly correlated Pfam families by the Šidák correction method Phenotype Description Anaerobic Organisms which do not grow in the presence of oxygen Bacillus or coccobacillu s Bacterial colony with Bacilli predominate with -highly pleomorphic and inconclusive morphology. Catalase To test for catalase activity, the bacteria to be tested are mixed with Hydrogen Peroxide. Catalase is an enzyme that catalyzes the breakdown of hydrogen peroxide to oxygen and water. Coccus A bacterium having a spherical or spheroidal shape. Coccus pairs or chains The predominant forms are cocci in chains or pairs. Summary of Results Only one prediction was highly significant according to Bonferroni and also found to be correct in our evaluation: PF02915.6 Rubrerythrin (Rr). According to the PFAM entry, this protein domain is found in anaerobic sulphate-reducing bacteria. According to Karlin et al. “the anaerobic delta genomes encode multiple copies of the anaerobic detoxification protein rubrerythrin that can neutralize hydrogen peroxide.” Additionally, Putz et al have identified rubrerythrin in the anaerobic organelles (hydrogenosomes) of parasitic flagellate Trichomonas vaginalis. Only one prediction was highly significant according to Bonferroni and also found to be incorrect in our evaluation: PF02388 - FemAB family negatively correlated with bacillus. According to the PFAM and PubMed entries, this protein domain involved in Staphylococcal species which are bacilli. The PFAM family PF00199 (catalase) was perfectly matched to the phenotype associated with catalase activity (p<0.019). The remainder of the predictions could be related to catalase via metabolism (catalytic activity). This is to be expected, as catalase breaks down the cytotoxic hydrogen peroxide byproduct of the electron transport chain. Another group of predictions relate histidine biosynthesis activity with catalase. There is anecdotal evidence that histidine biosynthesis and catalase activity are related in a variety of metabolic processes with over 300 publications in PubMed. Since only negatively correlated Pfam families are identified, which means that the 'coccus' phenotype is associated with the absence of these Pfam families. It suggests that the functions of these Pfam families are not involved in the phenotype. Since only negatively correlated Pfam families are identified, which means that this phenotype is associated with the absence of these Pfam families. It suggests that the functions of these Pfam families are Reference (s) Num. corre lated Pfam Num. positi vely correl ated Pfam Num. anticorrel ated Pfam 60 Corroborated Pfams out of a set of 100 reviewed Pfam [1,2] 1 1 0 PF02915.6 [3] [4,5] 1 0 1 [6] 15 15 0 N/A 10 0 10 N/A 6 0 6 PF00180.7 [7] PF00199.8 (#) not involved in the phenotype. predominate ColistinPolymyxin susceptible This is a particular susceptibility to the antibiotic colistin (polymyxin E), which are active against gram-negative bacteria. Curved bacilli Curved, comma or 'gull wing' rods. Does not include helical or spirochete forms There are 27 significant Pfam families predicted for this phenotype, and 14 of them are also found in the predicted Pfam families for ‘gram negative,’ such as 'Lipid-A-disaccharide synthetase', and ‘Phosphatidylglycerophosphatase A' that are involved in the lipopolysaccharide biosynthesis. There is only one PFAM family predicted for this phenotype. In PFAM this family includes functionally uncharacterized proteins from such pathogenic bacteria as Helicobacter pylori, Campylobacter jejuni, and Vibrio cholerae, of which all are 'curved bacilli'. [8,9] 27 27 0 N/A 1 1 0 PF03968.3 [10] PF04453.4 [10] PF04972.3 [11] D-Mannitol * Results from this class are explained in more detail in the section Results and Discussion Organisms which grow in the medium containing only DMannitol There are two Pfam families predicted. Both seem to be involved in mannitol metabolism. [12,13] 2 2 0 Organisms which grow both in the presence and absence of air All the three Pfam families are involved in the phosphotransferase system pathway, which is a major carbohydrate transport system in bacteria. [14-17] 3 3 0 PF02302.6 [18] PF00358.7 [18] PF04215.2 [17] 63 PF04279.4 [26] PF02321.6 [27] PF00529.8 [24] PF00593.10 [28] PF07715.1 [29] PF04413.3 [30] PF07660.2 [31] PF02684.5 [8] PF04613.2 [32] PF03331.3 [33] PF03279.3 [34] PF02348.6 [35] PF06293.3 [36] Facultative * Results from this class are explained in more detail in the section Results and Discussion Gram negative * Results from this class are explained in more detail in the section Results and Discussion Gram-negative forms predominate Gram positive Gram-positive forms predominate Growth on MacConkey agar is used for the As discussed in more detail in the paper, the most significant predicted Pfam families for the Gram negative are classified as lipopolysaccharide biosynthesis, lipopolysaccharide metabolism and lipid A biosynthesis, which are characteristics of Gram negative bacteria. Compared to the 'Gram positive', the positive correlated Pfam families (86 total) for the 'Gram negative' have a good correlation with the negative correlated Pfam families (24 total) for the 'Gram positive', of which 22 Pfam families are shared. On the other hand, there are 51 shared Pfam families between positively correlated 'Gram positive' Pfam families and negatively correlated 'Gram negative' Pfam families. Some of the top 10 Pfam families are found in the literature to be associated with 'Gram-positive' bacteria. Since this test is used to distinguish lactose fermenting [19-25] 149 86 [15,37] 110 86 24 PF04918.2 [38] PF04203.3 [39] PF02684.5 [8] PF04613.2 [32] PF03331.3 [40] PF03279.3 [34] PF02321.6 [27] [15,37,41] 111 110 1 PF00593.10 [42] MacConkey agar Growth on ordinary blood agar Indole L-Arabinose isolation of gram-negative enteric bacteria and the differentiation of lactose fermenting from lactose non-fermenting gram-negative bacteria. It has also become common to use the media to differentiate bacteria by their abilities to ferment sugars other than lactose. In these cases lactose is replaced in the medium by another sugar. It also inhibits growth of gram-positive bacteria. This describes a growth phenotype on a general purpose non-selective medium used commonly for cultures. Enriched with whole blood, it is used to isolate certain microorganisms and detect hemolytic activity. Indole is a component of the amino acid tryptophan, which some bacteria are able to metabolize using the enzyme tryptophanase. Indole is tested to determine tryptophan metabolism. This conventional biochemical testing consists on measuring the anaerobic acid production of the bacterial isolate in presence of a medium containing L_Arabinose and no other sugars. gram-negative bacteria, it shares a number of predictions with the 'Gram negative' phenotype. There are 26 positively correlated Pfam families shared between them. 7 out of top 10 most significant correlated Pfam families have unknown function, which may be of interest for further exploration. PF07715.1 [29] There was only one association with this phenotype and its relationship to the phenotype could not be established in the literature. N/A 1 1 0 The results associated to this phenotype were in the lower portion of our set near the statistical significance threshold. There was no clear pattern of association between the associated Pfam families and the phenotype. N/A 5 5 0 The predicted PFAM family L-arabinose isomerase is a perfect match with the L-Arabinose phenotype. N/A 1 1 0 This phenotype indicates the ability of the organisms to move, typically using flagella or cilia. The most significant PFAM families associated with this are involved in flagellar motility and chemotaxis. More details are descried in the paper. [43-59] 18 18 0 PF00460.8 (#) PF00669.8 (#) PF01584.8 [60] PF01514.7 [61] PF00771.7 [62] PF02154.5 (#) PF00700.8 (#) PF00813.7 [63] PF01052.8 [64] PF01311.8 [65] PF01312.8 [66] PF00015.10 (#) PF03963.3 (#) PF03705.5 [67] PF01739.8 [67] PF01313.7 [53] ONPG is a lactose analog used to test for beta galactosidase The PFAM family found to be associated with this phenotype includes beta galacosidase, which facilitates [68-73] 1 1 0 PF00703.9 [74] Motile Results from this class are explained in more detail in the section Results and Discussion and in Tables 4A and 4B ONPG (beta galactosidas e) Oxidase activity. the hydrolysis of ONPG. Proteins with oxidase activity participate in a reduction/oxidation reaction where atmospheric oxygen is the electron acceptor The two Pfam families PF02630.4 and PF00033.8, are a mitochondrion-associated cytochrome c oxidase assembly factor and a component of respiratory chain complex III (which has oxidoreductase activity), respectively. Both are directly associated to oxidase activity. Spore formation This phenotype includes proteins involved in the development of spores. Except for two Pfam families that have unknown functions, the remaining 9 PFAM families, constituted of proteins involved in spore development as well as structure, are found to be directly related to this phenotype. Strictly aerobic This phenotype describes the ability of organisms to grow only in the presence of air. Only a single Pfam prediction was found for this phenotype: "Bacterial signaling protein N terminal repeat." According to Galperin et al. it is found exclusively in aerobic or facultative aerobic bacteria. Urea hydrolysis This phenotype describes an organism’s ability to perform the breakdown of Urea by the enzyme Urease to form ammonia and carbamine acid. The two Pfam families found significantly associated to this phenotype form some of the subdomains of the Urease enzyme, which is involved in urea hydrolysis. [75-78] 2 2 0 PF02630.4 [79] PF06898.1 (#) PF03323.3 (#) PF03419.3 (#) PF03862.3 (#) PF05504.1 (#) PF05580.2 [84] PF05582.2 [85] PF07451.1 (#) PF07454.1 (#) [70,80-86] 11 11 0 [87] 1 1 0 [88-92] 2 2 0 PF02814.5 (#) PF05194.2 (#) Legend: # denotes self-evident relationships References: 1. Karlin S, Brocchieri L, Mrazek J, Kaiser D (2006) Distinguishing features of delta-proteobacterial genomes. Proc Natl Acad Sci U S A 103: 11352-11357. 2. Putz S, Gelius-Dietrich G, Piotrowski M, Henze K (2005) Rubrerythrin and peroxiredoxin: two novel putative peroxidases in the hydrogenosomes of the microaerophilic protozoon Trichomonas vaginalis. Mol Biochem Parasitol 142: 212-223. 3. Bateman A, Coin L, Durbin R, Finn RD, Hollich V, et al. Rubrerythrin. (PF02915) The Pfam Protein Families Database. http://pfam.wustl.edu/cgibin/getdesc?name=Rubrerythrin 4. Vannuffel P, Heusterspreute M, Bouyer M, Vandercam B, Philippe M, et al. (1999) Molecular characterization of femA from Staphylococcus hominis and Staphylococcus saprophyticus, and femA-based discrimination of staphylococcal species. Res Microbiol 150: 129-141. 5. Ehlert K, Schroder W, Labischinski H (1997) Specificities of FemA and FemB for different glycine residues: FemB cannot substitute for FemA in staphylococcal peptidoglycan pentaglycine side chain formation. J Bacteriol 179: 7573-7576. 6. Bai J, Cederbaum AI (2001) Mitochondrial catalase and oxidative injury. Biol Signals Recept 10: 189-199. 7. Bateman A, Coin L, Durbin R, Finn RD, Hollich V, et al. Isocitrate/isopropylmalate dehydrogenase. (PF00180) The Pfam Protein Families Database. http://www.sanger.ac.uk/cgi-bin/Pfam/getacc?PF00180 8. Crowell DN, Reznikoff WS, Raetz CR (1987) Nucleotide sequence of the Escherichia coli gene for lipid A disaccharide synthase. J Bacteriol 169: 5727-5734. 9. Funk CR, Zimniak L, Dowhan W (1992) The pgpA and pgpB genes of Escherichia coli are not essential: evidence for a third phosphatidylglycerophosphate phosphatase. J Bacteriol 174: 205-213. 10. Aono R, Negishi T, Nakajima H (1994) Cloning of organic solvent tolerance gene ostA that determines n-hexane tolerance level in Escherichia coli. Appl Environ Microbiol 60: 4624-4626. 11. Bateman A, Coin L, Durbin R, Finn RD, Hollich V, et al. Putative phospholipid-binding domain. (PF04972) The Pfam Protein Families Database. http://www.sanger.ac.uk//cgi-bin/Pfam/getacc?PF04972 12. Fischer R, von Strandmann RP, Hengstenberg W (1991) Mannitol-specific phosphoenolpyruvate-dependent phosphotransferase system of Enterococcus faecalis: molecular cloning and nucleotide sequences of the enzyme IIIMtl gene and the mannitol-1-phosphate dehydrogenase gene, expression in Escherichia coli, and comparison of the gene products with similar enzymes. J Bacteriol 173: 3709-3715. 13. Schneider KH, Giffhorn F, Kaplan S (1993) Cloning, nucleotide sequence and characterization of the mannitol dehydrogenase gene from Rhodobacter sphaeroides. J Gen Microbiol 139: 2475-2484. 14. Meadow ND, Fox DK, Roseman S (1990) The bacterial phosphoenolpyruvate: glycose phosphotransferase system. Annu Rev Biochem 59: 497-542. 15. Ab E, Schuurman-Wolters G, Reizer J, Saier MH, Dijkstra K, et al. (1997) The NMR side-chain assignments and solution structure of enzyme IIBcellobiose of the phosphoenolpyruvate-dependent phosphotransferase system of Escherichia coli. Protein Sci 6: 304-314. 16. Postma PW, Lengeler JW, Jacobson GR (1993) Phosphoenolpyruvate:carbohydrate phosphotransferase systems of bacteria. Microbiol Rev 57: 543-594. 17. Yew WS, Gerlt JA (2002) Utilization of L-ascorbate by Escherichia coli K-12: assignments of functions to products of the yjf-sga and yia-sgb operons. J Bacteriol 184: 302-306. 18. Bateman A, Coin L, Durbin R, Finn RD, Hollich V, et al. phosphoenolpyruvate-dependent sugar phosphotransferase system, EIIA 1: "The phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS) PUBMED:8246840, PUBMED:2197982 is a major carbohydrate transport system in bacteria. " (PF00358) The Pfam Protein Families Database. http://www.sanger.ac.uk/cgi-bin/Pfam/getacc?PF00358 19. Stevenson G, Andrianopoulos K, Hobbs M, Reeves PR (1996) Organization of the Escherichia coli K-12 gene cluster responsible for production of the extracellular polysaccharide colanic acid. J Bacteriol 178: 4885-4893. 20. Yethon JA, Whitfield C (2001) Purification and characterization of WaaP from Escherichia coli, a lipopolysaccharide kinase essential for outer membrane stability. J Biol Chem 276: 5498-5504. 21. Johnson JM, Church GM (1999) Alignment and structure prediction of divergent protein families: periplasmic and outer membrane proteins of bacterial efflux pumps. J Mol Biol 287: 695-715. 22. Duong F, Lazdunski A, Cami B, Murgier M (1992) Sequence of a cluster of genes controlling synthesis and secretion of alkaline protease in Pseudomonas aeruginosa: relationships to other secretory pathways. Gene 121: 47-54. 23. Gilson L, Mahanty HK, Kolter R (1990) Genetic analysis of an MDR-like export system: the secretion of colicin V. Embo J 9: 3875-3884. 24. Letoffe S, Delepelaire P, Wandersman C (1990) Protease secretion by Erwinia chrysanthemi: the specific secretion functions are analogous to those of Escherichia coli alpha-haemolysin. Embo J 9: 1375-1382. 25. Stoddard GW, Petzel JP, van Belkum MJ, Kok J, McKay LL (1992) Molecular analyses of the lactococcin A gene cluster from Lactococcus lactis subsp. lactis biovar diacetylactis WM4. Appl Environ Microbiol 58: 1952-1961. 26. Gilleland HE, Jr., Murray RG (1975) Demonstration of cell division by septation in a variety of gram-negative rods. J Bacteriol 121: 721-725. 27. Bateman A, Coin L, Durbin R, Finn RD, Hollich V, et al. Outer membrane efflux protein: "The OEP family (Outer membrane efflux protein) form trimeric channels that allow export of a variety of substrates in Gram negative bacteria." (PF02321) The Pfam Protein Families Database. http://www.sanger.ac.uk//cgi-bin/Pfam/getacc?PF02321 28. Chimento DP, Kadner RJ, Wiener MC (2003) The Escherichia coli outer membrane cobalamin transporter BtuB: structural analysis of calcium and substrate binding, and identification of orthologous transporters by sequence/structure conservation. J Mol Biol 332: 999-1014. 29. Oke M, Sarra R, Ghirlando R, Farnaud S, Gorringe AR, et al. (2004) The plug domain of a neisserial TonB-dependent transporter retains structural integrity in the absence of its transmembrane beta-barrel. FEBS Lett 564: 294-300. 30. Brabetz W, Muller-Loennies S, Brade H (2000) 3-Deoxy-D-manno-oct-2-ulosonic acid (Kdo) transferase (WaaA) and kdo kinase (KdkA) of Haemophilus influenzae are both required to complement a waaA knockout mutation of Escherichia coli. J Biol Chem 275: 34954-34962. 31. Burghout P, van Boxtel R, Van Gelder P, Ringler P, Muller SA, et al. (2004) Structure and electrophysiological properties of the YscC secretin from the type III secretion system of Yersinia enterocolitica. J Bacteriol 186: 4645-4654. 32. Kelly TM, Stachula SA, Raetz CR, Anderson MS (1993) The firA gene of Escherichia coli encodes UDP-3-O-(R-3-hydroxymyristoyl)-glucosamine Nacyltransferase. The third step of endotoxin biosynthesis. J Biol Chem 268: 19866-19874. 33. Bateman A, Coin L, Durbin R, Finn RD, Hollich V, et al. UDP-3-O-acyl N-acetylglycosamine deacetylase: "The enzymes in this family catalyse the second step in the biosynthetic pathway for lipid A. " (PF03331) The Pfam Protein Families Database. http://www.sanger.ac.uk//cgi-bin/Pfam/getacc?PF03331 34. Bateman A, Coin L, Durbin R, Finn RD, Hollich V, et al. Bacterial lipid A biosynthesis acyltransferase: "The bacterial lipid A biosynthesis protein, or lipid A biosynthesis (KDO)2-(lauroyl)-lipid IVA acyltransferase (EC 2.3.1.-), transfers myristate or laurate, activated on ACP, to the lipid IVA moiety of (KDO)2(lauroyl)-lipid IVA during lipopolysaccharide core biosynthesis. " (PF03279) The Pfam Protein Families Database. http://www.sanger.ac.uk//cgibin/Pfam/getacc?PF03279 35. Bateman A, Coin L, Durbin R, Finn RD, Hollich V, et al. Cytidylyltransferase: "Acylneuraminate cytidylyltransferase () (CMP-NeuAc synthetase) catalyzes the reaction of CTP and NeuAc to form CMP-NeuAc, which is the nucleotide sugar donor used by sialyltransferases PUBMED:8663048. The outer membrane lipooligosaccharides of some microorganisms contain terminal sialic acid attached to N-acetyllactosamine and so this modification may be important in pathogenesis." (PF02348) The Pfam Protein Families Database. http://www.sanger.ac.uk//cgi-bin/Pfam/getacc?PF02348 36. Bateman A, Coin L, Durbin R, Finn RD, Hollich V, et al. Lipopolysaccharide kinase (Kdo/WaaP) family: "These lipopolysaccharide kinases are related to protein kinases Pkinase. This family includes waaP (rfaP) gene product is required for the addition of phosphate to O-4 of the first heptose residue of the lipopolysaccharide (LPS) inner core region." (PF06293) The Pfam Protein Families Database. http://www.sanger.ac.uk//cgibin/Pfam/getacc?PF06293 37. Mazmanian SK, Liu G, Ton-That H, Schneewind O (1999) Staphylococcus aureus sortase, an enzyme that anchors surface proteins to the cell wall. Science 285: 760-763. 38. Debabov DV, Kiriukhin MY, Neuhaus FC (2000) Biosynthesis of lipoteichoic acid in Lactobacillus rhamnosus: role of DltD in D-alanylation. J Bacteriol 182: 2855-2864. 39. Cossart P, Jonquieres R (2000) Sortase, a universal target for therapeutic agents against gram-positive bacteria? Proc Natl Acad Sci U S A 97: 5013-5015. 40. Jackman JE, Fierke CA, Tumey LN, Pirrung M, Uchiyama T, et al. (2000) Antibacterial agents that target lipid A biosynthesis in gram-negative bacteria. Inhibition of diverse UDP-3-O-(r-3-hydroxymyristoyl)-n-acetylglucosamine deacetylases by substrate analogs containing zinc binding motifs. J Biol Chem 275: 11002-11009. 41. Forbes B, Sahm D, Weissfeld A (2002) Diagnostic Microbiology: Elsevier. 42. Bateman A, Coin L, Durbin R, Finn RD, Hollich V, et al. TonB dependent receptor: "the TonB protein interacts with outer membrane receptor proteins that carry out high-affinity binding and energy-dependent uptake of specific substrates into the periplasmic space ". (PF00593) The Pfam Protein Families Database. http://www.sanger.ac.uk/cgi-bin/Pfam/getacc?PF00593 43. Allaoui A, Sansonetti PJ, Parsot C (1992) MxiJ, a lipoprotein involved in secretion of Shigella Ipa invasins, is homologous to YscJ, a secretion factor of the Yersinia Yop proteins. J Bacteriol 174: 7661-7669. 44. Bilwes AM, Alex LA, Crane BR, Simon MI (1999) Structure of CheA, a signal-transducing histidine kinase. Cell 96: 131-141. 45. Bischoff DS, Ordal GW (1992) Identification and characterization of FliY, a novel component of the Bacillus subtilis flagellar switch complex. Mol Microbiol 6: 2715-2723. 46. DeRosier DJ (1995) Spinning tails. Curr Opin Struct Biol 5: 187-193. 47. Djordjevic S, Stock AM (1997) Crystal structure of the chemotaxis receptor methyltransferase CheR suggests a conserved structural motif for binding Sadenosylmethionine. Structure 5: 545-558. 48. Fedorov OV, Efimov AV (1990) Flagellin as an object for supramolecular engineering. Protein Eng 3: 411-413. 49. Gough CL, Genin S, Lopes V, Boucher CA (1993) Homology between the HrpO protein of Pseudomonas solanacearum and bacterial proteins implicated in a signal peptide-independent secretion mechanism. Mol Gen Genet 239: 378-392. 50. Homma M, Kutsukake K, Hasebe M, Iino T, Macnab RM (1990) FlgB, FlgC, FlgF and FlgG. A family of structurally related proteins in the flagellar basal body of Salmonella typhimurium. J Mol Biol 211: 465-477. 51. Komoriya K, Shibano N, Higano T, Azuma N, Yamaguchi S, et al. (1999) Flagellar proteins and type III-exported virulence factors are the predominant proteins secreted into the culture media of Salmonella typhimurium. Mol Microbiol 34: 767-779. 52. Lory S (1992) Determinants of extracellular protein secretion in gram-negative bacteria. J Bacteriol 174: 3423-3428. 53. Malakooti J, Ely B, Matsumura P (1994) Molecular characterization, nucleotide sequence, and expression of the fliO, fliP, fliQ, and fliR genes of Escherichia coli. J Bacteriol 176: 189-197. 54. Ohnishi K, Ohto Y, Aizawa S, Macnab RM, Iino T (1994) FlgD is a scaffolding protein needed for flagellar hook assembly in Salmonella typhimurium. J Bacteriol 176: 2272-2281. 55. Roman SJ, Frantz BB, Matsumura P (1993) Gene sequence, overproduction, purification and determination of the wild-type level of the Escherichia coli flagellar switch protein FliG. Gene 133: 103-108. 56. Suzuki H, Yonekura K, Murata K, Hirai T, Oosawa K, et al. (1998) A structural feature in the central channel of the bacterial flagellar FliF ring complex is implicated in type III protein export. J Struct Biol 124: 104-114. 57. Wandersman C (1992) Secretion across the bacterial outer membrane. Trends Genet 8: 317-322. 58. Wei ZM, Beer SV (1993) HrpI of Erwinia amylovora functions in secretion of harpin and is a member of a new protein family. J Bacteriol 175: 7958-7967. 59. Zhuang WY, Shapiro L (1995) Caulobacter FliQ and FliR membrane proteins, required for flagellar biogenesis and cell division, belong to a family of virulence factor export proteins. J Bacteriol 177: 343-356. 60. Bateman A, Coin L, Durbin R, Finn RD, Hollich V, et al. CheW-like domain. (PF01584) The Pfam Protein Families Database. http://www.sanger.ac.uk//cgibin/Pfam/getacc?PF01584 61. Bateman A, Coin L, Durbin R, Finn RD, Hollich V, et al. Secretory protein of YscJ/FliF family. (PF01514) The Pfam Protein Families Database. http://www.sanger.ac.uk//cgi-bin/Pfam/getacc?PF01514 62. Bateman A, Coin L, Durbin R, Finn RD, Hollich V, et al. FHIPEP family. (PF00771) The Pfam Protein Families Database. http://www.sanger.ac.uk//cgibin/Pfam/getacc?PF00771 63. Bateman A, Coin L, Durbin R, Finn RD, Hollich V, et al. FliP family. (PF00813) The Pfam Protein Families Database. http://www.sanger.ac.uk//cgibin/Pfam/getacc?PF00813 64. Bateman A, Coin L, Durbin R, Finn RD, Hollich V, et al. Surface presentation of antigens (SPOA) protein. (PF01052) The Pfam Protein Families Database. http://www.sanger.ac.uk//cgi-bin/Pfam/getacc?PF01052 65. Bateman A, Coin L, Durbin R, Finn RD, Hollich V, et al. Bacterial export proteins, family 1. (PF01311) The Pfam Protein Families Database. http://www.sanger.ac.uk//cgi-bin/Pfam/getacc?PF01311 66. Bateman A, Coin L, Durbin R, Finn RD, Hollich V, et al. FlhB HrpN YscU SpaS Family. (PF01312) The Pfam Protein Families Database. http://www.sanger.ac.uk//cgi-bin/Pfam/getacc?PF01312 67. Springer WR, Koshland DE, Jr. (1977) Identification of a protein methyltransferase as the cheR gene product in the bacterial sensing system. Proc Natl Acad Sci U S A 74: 533-537. 68. Davies G, Henrissat B (1995) Structures and mechanisms of glycosyl hydrolases. Structure 3: 853-859. 69. el Hassouni M, Henrissat B, Chippaux M, Barras F (1992) Nucleotide sequences of the arb genes, which control beta-glucoside utilization in Erwinia chrysanthemi: comparison with the Escherichia coli bgl operon and evidence for a new beta-glycohydrolase family including enzymes from eubacteria, archeabacteria, and humans. J Bacteriol 174: 765-777. 70. Fujita M, Losick R (2002) An investigation into the compartmentalization of the sporulation transcription factor sigmaE in Bacillus subtilis. Mol Microbiol 43: 27-38. 71. Henrissat B (1991) A classification of glycosyl hydrolases based on amino acid sequence similarities. Biochem J 280 ( Pt 2): 309-316. 72. Henrissat B, Bairoch A (1993) New families in the classification of glycosyl hydrolases based on amino acid sequence similarities. Biochem J 293 ( Pt 3): 781-788. 73. Henrissat B, Bairoch A (1996) Updating the sequence-based classification of glycosyl hydrolases. Biochem J 316 ( Pt 2): 695-696. 74. Coombs J, Brenchley JE (2001) Characterization of two new glycosyl hydrolases from the lactic acid bacterium Carnobacterium piscicola strain BA. Appl Environ Microbiol 67: 5094-5099. 75. Buchwald P, Krummeck G, Rodel G (1991) Immunological identification of yeast SCO1 protein as a component of the inner mitochondrial membrane. Mol Gen Genet 229: 413-420. 76. Buggy J, Bauer CE (1995) Cloning and characterization of senC, a gene involved in both aerobic respiration and photosynthesis gene expression in Rhodobacter capsulatus. J Bacteriol 177: 6958-6965. 77. Esposti MD, De Vries S, Crimi M, Ghelli A, Patarnello T, et al. (1993) Mitochondrial cytochrome b: evolution and structure of the protein. Biochim Biophys Acta 1143: 243-271. 78. Howell N (1989) Evolutionary conservation of protein regions in the protonmotive cytochrome b and their possible roles in redox catalysis. J Mol Evol 29: 157-169. 79. Bateman A, Coin L, Durbin R, Finn RD, Hollich V, et al. SCO1/SenC. (PF02630) The Pfam Protein Families Database. http://www.sanger.ac.uk//cgibin/Pfam/getacc?PF02630 80. Eichenberger P, Jensen ST, Conlon EM, van Ooij C, Silvaggi J, et al. (2003) The sigmaE regulon and the identification of additional sporulation genes in Bacillus subtilis. J Mol Biol 327: 945-972. 81. Paidhungat M, Setlow P (2000) Role of ger proteins in nutrient and nonnutrient triggering of spore germination in Bacillus subtilis. J Bacteriol 182: 25132519. 82. Tovar-Rojo F, Chander M, Setlow B, Setlow P (2002) The products of the spoVA operon are involved in dipicolinic acid uptake into developing spores of Bacillus subtilis. J Bacteriol 184: 584-587. 83. Hudson KD, Corfe BM, Kemp EH, Feavers IM, Coote PJ, et al. (2001) Localization of GerAA and GerAC germination proteins in the Bacillus subtilis spore. J Bacteriol 183: 4317-4322. 84. Hoa NT, Brannigan JA, Cutting SM (2001) The PDZ domain of the SpoIVB serine peptidase facilitates multiple functions. J Bacteriol 183: 4364-4373. 85. Takamatsu H, Imamura A, Kodama T, Asai K, Ogasawara N, et al. (2000) The yabG gene of Bacillus subtilis encodes a sporulation specific protease which is involved in the processing of several spore coat proteins. FEMS Microbiol Lett 192: 33-38. 86. Eichenberger P, Fawcett P, Losick R (2001) A three-protein inhibitor of polar septation during sporulation in Bacillus subtilis. Mol Microbiol 42: 1147-1162. 87. Galperin MY, Gaidenko TA, Mulkidjanian AY, Nakano M, Price CW (2001) MHYT, a new integral membrane sensor domain. FEMS Microbiology Letters 205: 17-23. 88. Ciurli S, Safarov N, Miletti S, Dikiy A, Christensen SK, et al. (2002) Molecular characterization of Bacillus pasteurii UreE, a metal-binding chaperone for the assembly of the urease active site. J Biol Inorg Chem 7: 623-631. 89. Colpas GJ, Hausinger RP (2000) In vivo and in vitro kinetics of metal transfer by the Klebsiella aerogenes urease nickel metallochaperone, UreE. J Biol Chem 275: 10731-10737. 90. Lee MH, Pankratz HS, Wang S, Scott RA, Finnegan MG, et al. (1993) Purification and characterization of Klebsiella aerogenes UreE protein: a nickelbinding protein that functions in urease metallocenter assembly. Protein Sci 2: 1042-1052. 91. Park IS, Hausinger RP (1995) Evidence for the presence of urease apoprotein complexes containing UreD, UreF, and UreG in cells that are competent for in vivo enzyme activation. J Bacteriol 177: 1947-1951. 92. Mulrooney SB, Ward SK, Hausinger RP (2005) Purification and properties of the Klebsiella aerogenes UreE metal-binding domain, a functional metallochaperone of urease. J Bacteriol 187: 3581-3585.