The E.faecalis pathogenicity island is 153 kbp and encodes 129 predicted ORFs. Present on this element are genes encoding for virulence factors, transposases, transcriptional regulators, and other proteins potentially involved in adaptation to diverse environments. Spread across the pathogenicity island are 11 transposases and insertion elements, with homology to ORFs from other low G+C gram-positive organisms such as E. faecium, S. aureus, Listeria innocua, L. monocytogenes, S. pneumoniae, and S. epidermidis. In addition, the 5' region of the pathogenicity island has extensive nucleotide sequence identity to the pheromone-responsive plasmids pAM373, pCF10, and pAD1 (EF0005-EF0026), suggesting integration of a pheromone-response plasmid. The only transfer-related genes present, however, comprise a TraG-like protein (EF0011) and a region with 87% identity at the nucleotide level to the second transfer origin (oriT) identified in pAD1.
Within the pathogenicity island are the virulence traits, Esp, cytolysin, and aggregation substance. In addition are a number of proteins that may have potential roles in virulence and/or environmental adaptation in E.faecalis. One of these traits is a putative bile salt hydrolase (cbh) (EF0040), which could add a new ecological niche to this E. faecalis strain, perhaps allowing growth in bile-rich environments such as the bile ducts, and therefore potentially giving this strain a competitive advantage. EF0040 has 67% similarity to the Bsh from L. monocytogenes, which is a bile salt hydrolase . In L. monocytogenes, Bsh is a virulence factor and is regulated by the virulence regulator PrfA . In vivo, deletion of this gene results in decreased fecal carriage in guinea pigs, and reduced liver colonization and virulence was noted in a mouse intravenous model . The contribution of cbh to the pathogenesis of enterococcal infections has not yet been investigated.
In terms of adaptation to different environments, in addition to the bile salt hydrolase, the pathogenicity island contains a phosphotransferase system (PTS) (EF0078-EF0081) and adjacent xylose metabolism genes (EF0082-EF0083), potentially allowing growth on xylose. Other metabolism genes include a ketopantoate reductase (EF0037), an ornithine cyclodeaminase (EF0124), a polysaccharide dea-cetylase (EF0108), and a glycosyl hydrolase (EF0077). These pathways may aid survival in nutrient limiting conditions, or in diverse environments. Additional mechanisms to cope with nutrient limiting conditions include a second putative manganese transporter with homology to EfaCBA, and a putative iron transporter (EF0095, EF0096), both of which may aid in survival in vivo.
As previously mentioned, two Gls24-like proteins are present on the pathogenicity island (EF0117 and EF0055). The Gls24 protein has been shown to be induced under certain stress conditions , and disruption of gls24 affects virulence in a mouse model . The exact function of Gls24 or its homologues is unknown.
Also potentially involved in stress response is a Dps-family surface protein (EF0119), with closest homology to Lactobacillus rhamnosus. Some members of this protein family have been shown to bind nonspecifically to DNA under starved conditions, protecting it from cleavage by reactive oxygen species . In addition a DNA-J homologue is present (EF0028), and a putative DNA-damage-induci-ble protein (EF0032). Potentially these three proteins may contribute to DNA repair and protection, and may have an important role in bacterial survival in harsh environmental conditions.
Encoded on the pathogenicity island is a putative potassium ABC transporter and a neighboring two-component regulatory system (EF0087-EF0091) with homology to the kdp operon from E. coli , but with closer identity to putative homologues in L. innocua. This operon may be involved in stress response to osmotic shock, allowing transport ofpotassium ions.
Other potential genes involved in virulence or environmental adaptation include a putative N-actylmannosamine-6-phosphate epimerase (EF0066), which is part of the N-acetylmannosamine utilization pathway, often found in oropharyngeal pathogens . In addition, a large cell-wall-associated protein is present (EF0109), with a predicted size of 207kDa. This large protein may have a role in colonization or virulence through adhesion or immune evasion, but its role is at present unknown.
Two genes (EF0120 and EF0122) present on the pathogenicity island have homology to IbrB, and IbrA, respectively, from E.coli . In E.coli these proteins are responsible for activation of the otherwise silent phage-derived eib genes, which bind immunoglobin . Interestingly, also on the pathogenicity island is a protein EF0052, with 49% similarity to the nisin-resistance protein from L. lactis subsp. lactis biovar diacetylactis DRC3, which has been demonstrated to be involved in resistance to nisin in this strain [127, 128]. In a study of S. agalactiae virulence using signature-tagged mutagenesis, two attenuated mutants were identified with insertions in an NisR homologue, although the function of this gene has not been characterized . As nisin is a cationic peptide, it is possible that this protein may confer cross-resistance to other cationic peptides such as defen-sins, or bacteriocins produced by other gut bacteria.
140 | 7 Pathogenomics of Enterococcusfaecalis 7.4
E.faecalis is a leading cause of nosocomial infection and this is probably associated with its ability both to survive in the hospital environment and also to overcome the harsh conditions associated with colonization and infection. In addition, over a quarter of the genome is mobile and acquired DNA, suggesting that this organism has the ability to rapidly acquire genetic information and evolve to adapt to its environment. The expeditious acquisition and dissemination of antimicrobial resistance in this organism has been previously demonstrated. Although several traits that contribute to virulence have been characterized in E.faecalis, little is known about the function of many of the potential virulence genes encoded both on the chromosome and in the pathogenicity island. The bacterial/host relationship is very complex, and the mechanisms that enterococci use to change from commensal organism to the etiologic agent of disease are not yet fully understood. However, with information from the genome sequence it is now possible to look closer at gene loci that may have important roles in this interaction.
1 Martin, J. D. and J. O. Mundt. 1972. Enterococci in insects. Appl. Microbiol. 24:575-580.
2 Rice, E. W., J. W. Messer, C. H. Johnson and D. J. Reasoner. 1995. Occurrence of high-level aminoglycoside resistance in environmental isolates of enterococci. Appl. Environ. Microbiol. 61:374-376.
3 Schaberg, D. R., D. H. Culver and R. P. Gaynes. 1991. Major trends in the microbial etiology ofnosocomial infection. Am. J. Med. 91:72S-75S.
4 Gordon, K. A. and R. N. Jones. 2003. Susceptibility patterns of orally administered antimicrobials among urinary tract infection pathogens from hospitalized patients in North America: comparison report to Europe and Latin America. Results from the SENTRY Antimicrobial Surveillance Program (2000). Diagn. Microbiol. Infect. Dis. 45:295-301.
5 National Nosocomial Infections Surveillance System. 1999. National Nosocomial Infections Surveillance (NNIS) System report, data summary from January 1990-May 1999, issued June 1999. Am. J. Infect. Control 27:520-532.
6 Low, D. E., N. Keller, A. Barth and R. N. Jones. 2001. Clinical prevalence, antimicrobial susceptibility, and geographic resistance patterns of enterococci: results from the SENTRY Antimicrobial Surveillance Program, 1997-1999. Clin. Infect. Dis. 32:133-145.
7 Sahm, D. F., J. Kissinger, M. S. Gil-more, P. R. Murray, R. Mulder, J. Solli-day and B. Clarke. 1989. In vitro susceptibility studies of vancomycin-resistant Enterococcusfaecalis. Antimicrob. Agents Chemother. 33:1588-1591.
8 Paulsen, I. T., L. Banerjei, G. S. Myers, K. E. Nelson, R. Seshadri, T. D. Read, D. E. Fouts, J. A. Eisen, S. R. Gill, J. F. Heidelberg et al. 2003. Role of mobile DNA in the evolution of vancomycin-resistant Enterococcusfaecalis. Science 299:2071-2074.
9 Shankar, N., A. S. Baghdayan and M. S. Gilmore. 2002. Modulation of virulence within a pathogenicity island in vanco-mycin-resistant Enterococcusfaecalis. Nature 417:746-750.
10 Singh, K. V. and B. E. Murray. 1994. Revised estimates of enterococcal chro mosomal sizes. DNA Cell. Biol. 13:1145-1146.
11 Oana, K., Y. Okimura, Y. Kawakami, N. Hayashida, M. Shimosaka, M. Oka-zaki, T. Hayashi and M. Ohnishi. 2002. Physical and genetic map of Enterococcus faecium ATCC19434 and demonstration of intra- and interspecific genomic diversity in enterococci. FEMS Microbiol. Lett. 207:133-139.
12 Hayashi, T., K. Makino, M. Ohnishi, K. Kurokawa, K. Ishii, K. Yokoyama,
C. G. Han, E. Ohtsubo, K. Nakayama, T. Murata et al. 2001. Complete genome sequence of enterohemorrhagic Escherichia coli O157:H7 and genomic comparison with a laboratory strain K-12. DNA Res. 8:11-22.
13 Nelson, K. E., D. E. Fouts, E. F. Mongo-din, J. Ravel, R. T. DeBoy, J. F. Kolonay,
I. T. Paulsen et al. 2004. Whole genome comparisons of serotype 4b and 1/2a strains of the food-borne pathogen Listeria monocytogenes reveal new insights into the core genome components of this species. Nucleic Acids Res. 32:2386-2395.
14 Novak, R., E. Charpentier, J. S. Braun and E. Tuomanen. 2000. Signal trans-duction by a death signal peptide: uncovering the mechanism ofbacterial killing by penicillin. Mol. Cell. 5:49-57.
15 Robertson, G. T., J. Zhao, B. V. Desai, W. H. Coleman, T. I. Nicas, R. Gilmour, L. Grinius, D. A. Morrison and M. E. Winkler. 2002. Vancomycin tolerance induced by erythromycin but not by loss of vncRS, vex3, or pep27 function in Streptococcus pneumoniae. J. Bacteriol. 184:6987-7000.
16 Haas, W., J. Sublett, D. Kaushal and E. I. Tuomanen. 2004. Revising the role of the pneumococcal vex-vncRS locus in vancomycin tolerance. J. Bacteriol. 186:8463-8471.
17 Bensing, B. A., I. R. Siboo and P. M. Sullam. 2001. Proteins PblA and PblB of Streptococcus mitis, which promote binding to human platelets, are encoded within a lysogenic bacteriophage. Infect. Immun. 69:6186-6192.
18 Smoot, J. C., K. D. Barbian, J. J. Van Gompel, L. M. Smoot, M. S. Chaussee,
G. L. Sylva, D. E. Sturdevant, S. M. Rick-lefs, S. F. Porcella, L. D. Parkins et al. 2002. Genome sequence and comparative microarray analysis of serotype M18 group A Streptococcus strains associated with acute rheumatic fever outbreaks. Proc. Natl. Acad. Sci. U. S.A. 99:46684673.
19 Kozitskaya, S., S. H. Cho, K. Dietrich, R. Marre, K. Naber and W. Ziebuhr. 2004. The bacterial insertion sequence element IS256 occurs preferentially in nosocomial Staphylococcus epidermidis isolates: association with biofilm formation and resistance to aminoglycosides. Infect. Immun. 72:1210-1215.
20 Kiem, S., W. S. Oh, K. R. Peck, N. Y. Lee, J. Y. Lee, J. H. Song, E. S. Hwang, E. C. Kim, C. Y. Cha and K. W. Choe. 2004. Phase variation of biofilm formation in Staphylococcus aureus by IS256 insertion and its impact on the capacity adhering to polyurethane surface.
21 Conlon, K. M., H. Humphreys and J. P. O'Gara. 2004. Inactivations of rsbUand sarA by IS256 represent novel mechanisms ofbiofilm phenotypic variation in Staphylococcus epidermidis. J. Bacteriol. 186:6208-6219.
22 Chain, P. S., E. Carniel, F. W. Larimer, J. Lamerdin, P. O. Stoutland, W. M. Regala, A. M. Georgescu, L. M. Vergez, M. L. Land, V. L. Motin et al. 2004. Insights into the evolution of Yersinia pestis through whole-genome comparison with Yersinia pseudotuberculosis. Proc. Natl. Acad. Sci. U. S.A. 101:13826-13831.
E. Samberger, A. Muscholl-Silberhorn, M. S. Gilmore, Y. Ike, K. E. Weaver, F. Y. An and D. B. Clewell. 2001. Completion of the nucleotide sequence of the Enterococcus faecalis conjugative virulence plas-mid pAD1 and identification of a second transfer origin. Plasmid 46:117127.
C. M. Fraser. 2000. Enterococcus faecalis conjugative plasmid pAM373: complete nucleotide sequence and genetic analyses of sex pheromone response. Mol. Microbiol. 37:1327-1341.
25 Dunny, G. M. and B. A. Leonard. 1997. Cell-cell communication in gram-positive bacteria. Annu. Rev. Microbiol. 51:527-564.
26 Evers, S., D. F. Sahm and P. Courvalin. 1993. The vanB gene ofvancomycin-resistant Enterococcus faecalis V583 is structurally related to genes encoding D-Ala:D-Ala ligases and glycopeptide-resistance proteins VanA and VanC. Gene 124:143-144.
P. Courvalin and M. Galimand. 2000. Characterization of transposon Tnl549, conferring VanB-type resistance in Enterococcus spp. Microbiology 146:1481-1489.
C. Rusniok, A. Amend, F. Baquero, P. Berche, H. Bloecker, P. Brandt,
T. Chakraborty et al. 2001. Comparative genomics of Listeria species. Science 294:849-852.
O. Jaillon, K. Malarme, J. Weissenbach, S. D. Ehrlich and A. Sorokin. 2001. The complete genome sequence of the lactic acid bacterium Lactococcus lactis ssp. lac-tis IL1403. Genome Res. 11:731-753.
D. J. Savic, G. Savic, K. Lyon, C. Pri-meaux, S. Sezate, A. N. Suvorov, S. Kenton et al. 2001. Complete genome sequence of an M1 strain of Streptococcus pyogenes. Proc. Natl. Acad. Sci. U.S.A. 98:4658-4663.
31 Borezee, E., T. Msadek, L. Durant and P. Berche. 2000. Identification in Listeria monocytogenes of MecA, a homologue ofthe Bacillus subtilis competence regulatory protein. J. Bacteriol. 182:5931-5934.
32 Jones, C. H., T. C. Bolken, K. F. Jones, G. O. Zeller and D. E. Hruby. 2001. Conserved DegP protease in gram-positive bacteria is essential for thermal and oxidative tolerance and full virulence in Streptococcus pyogenes. Infect. Immun. 69:5538-5545.
33 Brenot, A., K. Y. King, B. Janowiak, O. Griffith and M. G. Caparon. 2004. Contribution of glutathione peroxidase to the virulence of Streptococcus pyogenes. Infect. Immun. 72:408-413.
34 Halsey, T. A., A. Vazquez-Torres, D. J. Gravdahl, F. C. Fang and S. J. Libby. 2004. The ferritin-like Dps protein is required for Salmonella enterica serovar Typhimurium oxidative stress resistance and virulence. Infect. Immun. 72:11551158.
35 Brown, J. S., S. M. Gilliland, S. Basa-vanna and D. W. Holden. 2004. phgABC, a three-gene operon required for growth of Streptococcus pneumoniae in hyperosmotic medium and in vivo. Infect. Immun. 72:4579-4588.
36 Casiano-Colon, A. and R. E. Marquis. 1988. Role of the arginine deiminase system in protecting oral bacteria and an enzymatic basis for acid tolerance. Appl. Environ. Microbiol. 54:1318-1324.
37 Sukharev, S. I., P. Blount, B. Martinac and C. Kung. 1997. Mechanosensitive channels of Escherichia coli: the MscL gene, protein, and activities. Annu. Rev. Physiol. 59:633-657.
38 Agranoff, D. D. and S. Krishna. 1998. Metal ion homeostasis and intracellular parasitism. Mol. Microbiol. 28:403-412.
39 Laport, M. S., J. A. Lemos, C. Bastos Md Mdo, R. A. Burne and M. Giambiagi-De Marval. 2004. Transcriptional analysis of the groE and dnaK heat-shock operons of Enterococcus faecalis. Res. Microbiol. 155:252-258.
40 Derre, I., G. Rapoport and T. Msadek. 1999. CtsR, a novel regulator of stress and heat shock response, controls clp and molecular chaperone gene expression in gram-positive bacteria. Mol. Microbiol. 31:117-131.
41 Krüger, E., E. Witt, S. Ohlmeier, R. Hanschke and M. Hecker. 2000. The clp proteases of Bacillus subtilis are directly involved in degradation of mis-folded proteins. J. Bacteriol. 182:32593265.
T. Msadek. 2004. clpB, a novel member of the Listeria monocytogenes CtsR regu-lon, is involved in virulence but not in general stress tolerance. J. Bacteriol. 186:1165-1174.
43 Diaz-Torres, M. L. and R. R. Russell. 2001. HtrA protease and processing of extracellular proteins of Streptococcus mutans. FEMS Microbiol. Lett. 204:2328.
44 Lyon, W. R. and M. G. Caparon. 2004. Role for serine protease HtrA (DegP) of Streptococcus pyogenes in the biogenesis of virulence factors SpeB and the hemolysin streptolysin S. Infect. Immun. 72:1618-1625.
45 Ibrahim, Y. M., A. R. Kerr, J. McCluskey and T. J. Mitchell. 2004. Role of HtrA in the virulence and competence of Streptococcus pneumoniae. Infect. Immun. 72:3584-3591.
Y. Auffray and A. Hartke. 2000. Inactiva-tion ofthe stress- and starvation-induci-ble gls24 operon has a pleiotrophic effect on cell morphology, stress sensitivity, and gene expression in Enterococcus fae-calis. J. Bacteriol. 182:4512-4520.
47 Shepard, B. D. and M. S. Gilmore. 2002. Differential expression of virulence-related genes in Enterococcus faecalis in response to biological cues in serum and urine. Infect. Immun. 70:43444352.
48 Teng, F., E. C. Nannini and B. E. Murray. 2005. Importance of gls24 in virulence and stress response of Enterococ-cusfaecalis and use of the Gls24 protein as a possible immunotherapy target.
S. Lemarinier, Y. Auffray and A. Rincé. 2002. Isolation and characterization of bile salts-sensitive mutants of Enterococ-cusfaecalis. Curr. Microbiol. 45:434-439.
50 Sleator, R. D., H. H. Wemekamp-Kam-huis, C. G. M. Gahan, T. Abee and
C. Hill. 2005. A PrfA-regulated bile extrusion system (BilE) is a novel virulence factor in Listeria monocytogenes. Mol. Microbiol. 55:1183-1195.
51 Huycke, M. M. 2002. Physiology of enterococci. In: The Enterococci: Pathogenesis, Molecular Biology, and Antibiotic Resistance. M. S. Gilmore, D. B. Cle-well, P. Courvalin, G. M. Dunny, B. E. Murray, and L. B. Rice, editors. ASM Press, Washington, DC, 133-175.
S. Flahaut and Y. Auffray. 2001. Identification and characterization of gsp65, an organic hydroperoxide resistance (ohr)
gene encoding a general stress protein in Enterococcusfaecalis. J. Bacteriol. 183:1482-1488.
53 Frankenberg, L., M. Brugna and
L. Hederstedt. 2002. Enterococcus faecalis heme-dependent catalase. J. Bacteriol. 184:6351-6356.
54 Huycke, M. M., V. Abrams and D. R. Moore. 2002. Enterococcus faecalis produces extracellular superoxide and hydrogen peroxide that damages colonic epithelial cell DNA. Carcinogenesis 23:529-536.
P. Wise, L. Shepard, Y. Kotake and M. S. Gilmore. 2001. Extracellular superoxide production by Enterococcus faecalis requires demethylmenaquinone and is attenuated by functional terminal qui-nol oxidases. Mol. Microbiol. 42:729740.
56 Huycke, M. M., W. Joyce and M. F. Wack. 1996. Augmented production of extracellular superoxide by blood isolates of Enterococcus faecalis. J. Infect. Dis. 173:743-746.
57 Stock, A. M., V. L. Robinson and P. N. Goudreau. 2000. Two-component signal transduction. Annu. Rev. Biochem. 69:183-215.
58 Hancock, L. E. and M. Perego. 2004. Systematic inactivation and phenotypic characterization of two-component signal transduction systems of Enterococcus faecalis V583. J. Bacteriol. 186:79517958.
L. Dubost, J. P. Brouard, J. E. Hugonnet and M. Arthur. 2003. The CroRS two-component regulatory system is required for intrinsic beta-lactam resistance in Enterococcus faecalis. J. Bacter-iol. 185:7184-7192.
60 Le Breton, Y., G. Boel, A. Benachour, H. Prevost, Y. Auffray and A. Rincé. 2003. Molecular characterization of Enterococcus faecalis two-component signal transduction pathways related to environmental stresses. Environ. Micro-biol. 5:329-337.
61 Teng, F., L. Wang, K. V. Singh, B. E. Murray and G. M. Weinstock. 2002. Involvement of PhoP-PhoS homologs in
Enterococcusfaecalis virulence. Infect. Immun. 70:1991-1996.
62 Verneuil, N., M. Sanguinetti, Y. Le Breton, B. Posteraro, G. Fadda, Y. Auffray, A. Hartke and J. C. Giard. 2004. Effects of the Enterococcusfaecalis hypR gene encoding a new transcriptional regulator on oxidative stress response and intracellular survival within macrophages. Infect. Immun. 72:4424-4431.
63 Schauder, S. and B. L. Bassler. 2001. The language of bacteria. Genes Dev. 15:1468-1480.
64 Marouni, M. J. and S. Sela. 2003. The luxS gene of Streptococcus pyogenes regulates expression ofgenes that affect internalization by epithelial cells. Infect. Immun. 71:5633-5639.
65 Lowe, A. M., P. A. Lambert and A. W. Smith. 1995. Cloning of an Enterococcus faecalis endocarditis antigen: homology with adhesins from some oral streptococci. Infect. Immun. 63:703-706.
66 Singh, K. V., T. M. Coque, G. M. Weinstock and B. E. Murray. 1998. In vivo testing of an Enterococcusfaecalis efaA mutant and use of efaA homologs for species identification. FEMS Immunol. Med. Microbiol. 21:323-331.
67 Kolenbrander, P. E., R. N. Andersen, R. A. Baker and H. F. Jenkinson. 1998. The adhesion-associated sca operon in Streptococcus gordonii encodes an induci-ble high-affinity ABC transporter for Mn2+ uptake. J. Bacteriol. 180:290-295.
68 Jakubovics, N. S., A. W. Smith and H. F. Jenkinson. 2000. Expression of the virulence-related Sca (Mn ) permease in Streptococcus gordonii is regulated by a diphtheria toxin metallorepressor-like protein ScaR. Mol. Microbiol. 38:140153.
69 Low, Y. L., N. S. Jakubovics, J. C. Flat-man, H. F. Jenkinson and A. W. Smith. 2003. Manganese-dependent regulation of the endocarditis-associated virulence factor EfaA of Enterococcusfaecalis.
J. Med. Microbiol. 52:113-119.
70 Baida, G. E. and N. P. Kuzmin. 1995. Cloning and primary structure of a new hemolysin gene from Bacillus cereus. Biochim. Biophys. Acta. 1264:151-154.
71 Hashimoto, W., H. Nankai, B. Mikami and K. Murata. 2003. Crystal structure of Bacillus sp. GL1 xanthan lyase, which acts on the side chains of xanthan. J. Biol. Chem. 278:7663-7673.
72 Ponnuraj, K. and M. J. Jedrzejas. 2000. Mechanism of hyaluronan binding and degradation: structure of Streptococcus pneumoniae hyaluronate lyase in complex with hyaluronic acid disaccharide at 1.7 A resolution. J. Mol. Biol. 299:885-895.
73 Kreil, G. 1995. Hyaluronidases - a group ofneglected enzymes. Protein Sci. 4:1666-1669.
74 Makinen, P. L., D. B. Clewell, F. An and K. K. Makinen. 1989. Purification and substrate specificity of a strongly hydro-phobic extracellular metalloendopepti-dase ("gelatinase") from Streptococcus faecalis (strain 0G1-10). J. Biol. Chem. 264:3325-34.
75 Bleiweis, A. S. and L. N. Zimmerman. 1964. Properties of proteinase from Streptococcus faecalis Var. liquefaciens.
J. Bacteriol. 88:653-659.
76 Waters, C. M., M. H. Antiporta, B. E. Murray and G. M. Dunny. 2003. Role of the Enterococcus faecalis GelE protease in determination of cellular chain length, supernatant pheromone levels, and degradation of fibrin and misfolded surface proteins. J. Bacteriol. 185:3613-3623.
77 Singh, K. V., X. Qin, G. M. Weinstock and B. E. Murray. 1998. Generation and testing of mutants of Enterococcus faeca-lis in a mouse peritonitis model.
J. Infect. Dis. 178:1416-1420.
78 Engelbert, M., E. Mylonakis, F. M. Ausubel, S. B. Calderwood and M. S. Gilmore. 2004. Contribution of gelatinase, serine protease, and fsr to the pathogenesis of Enterococcusfaecalis endophthalmitis. Infect. Immun. 72:3628-3633.
79 Sifri, C. D., E. Mylonakis, K. V. Singh, X. Qin, D. A. Garsin, B. E. Murray, F. M. Ausubel and S. B. Calderwood. 2002. Virulence effect of Enterococcusfaecalis protease genes and the quorum-sensing locus fsr in Caenorhabditis elegans and mice. Infect. Immun. 70:5647-5650.
J. Travis and B. E. Murray. 2005. Molecular diversity of a putative virulence factor: purification and characterization of isoforms of an extracellular serine glutamyl endopeptidase of Enterococcusfaeca-lis with different enzymatic activities. J. Bacteriol. 187:266-275.
81 Qin, X., K. V. Singh, G. M. Weinstock and B. E. Murray. 2000. Effects of Enter-ococcus faecalis fsr genes on production of gelatinase and a serine protease and virulence. Infect. Immun. 68:25792586.
82 Jha, A. K., H. P. Bais and J. M. Vivanco. 2005. Enterococcusfaecalis mammalian virulence-related factors exhibit potent pathogenicity in the Arabidopsis thaliana plant model. Infect. Immun. 73:464475.
83 Qin, X., K. V. Singh, G. M. Weinstock and B. E. Murray. 2001. Characterization offsr, a regulator controlling expression ofgelatinase and serine protease in Enterococcusfaecalis OG1RF. J. Bacteriol. 183:3372-3382.
S. Sakuda, A. D. Akkermans, W. M. de Vos and H. Nagasawa. 2001. Gelatinase biosynthesis-activating pheromone: a peptide lactone that mediates a quorum sensing in Enterococcusfaecalis. Mol. Microbiol. 41:145-154.
85 Gilmore, M. S., P. S. Coburn, S. R. Nal-lapareddy and B. E. Murray. 2002. Enter-ococcal virulence. In: The Enterococci: Pathogenesis, Molecular Biology, and Antibiotic Resistance. M. S. Gilmore,
D. B. Clewell, P. Courvalin, G. M. Dunny, B. E. Murray, and L. B. Rice, editors. ASM Press, Washington, DC, 301-354.
86 Hancock, L. E. and M. Perego. 2004. The Enterococcus faecalis fsr two-component system controls biofilm development through production ofgelatinase. J. Bacteriol. 186:5629-5639.
87 An, F. Y., M. C. Sulavik and D. B. Cle-well. 1999. Identification and characterization of a determinant (eep) on the Enterococcusfaecalis chromosome that is involved in production of the peptide sex pheromone cAD1. J. Bacteriol. 181:5915-5921.
88 Gilmore, M. S., R. A. Segarra, M. C. Booth, C. P. Bogie, L. R. Hall and D. B. Clewell. 1994. Genetic structure of the Enterococcusfaecalis plasmid pAD1-
encoded cytolytic toxin system and its relationship to lantibiotic determinants. J. Bacteriol. 176:7335-7344.
T. Uji, K. Yamaguchi and S. Goto. 1993. Cytotoxic effect of hemolytic culture supernatant from Enterococcusfaecalis on mouse polymorphonuclear neutrophils and macrophages. Microbiol. Immunol. 37:265-270.
90 Coburn, P. S., C. M. Pillar, B. D. Jett, W. Haas and M. S. Gilmore. 2004. Enter-ococcus faecalis senses target cells and in response expresses cytolysin. Science 306:2270-2272.
91 Ike, Y., H. Hashimoto and D. B. Clewell. 1984. Hemolysin of Streptococcus faecalis subspecies zymogenes contributes to virulence in mice. Infect. Immun. 45:528-530.
92 Chow, J. W., L. A. Thal, M. B. Perri, J. A. Vazquez, S. M. Donabedian, D. B. Clewell and M. J. Zervos. 1993. Plasmid-associated hemolysin and aggregation substance production contribute to virulence in experimental enterococcal endocarditis. Antimicrob. Agents Chemother. 37:2474-2477.
93 Jett, B. D., H. G. Jensen, R. E. Nordquist and M. S. Gilmore. 1992. Contribution of the pAD1-encoded cytolysin to the severity of experimental Enterococcusfaecalis endophthalmitis. Infect. Immun. 60:2445-2452.
94 Garsin, D. A., C. D. Sifri, E. Mylonakis, X. Qin, K. V. Singh, B. E. Murray, S. B. Calderwood and F. M. Ausubel. 2001. A simple model host for identifying Gram-positive virulence factors. Proc. Natl. Acad. Sci. U. S. A. 98:1089210897.
95 Sillanpaa, J., Y. Xu, S. R. Nallapareddy, B. E. Murray and M. Hook. 2004. A family of putative MSCRAMMs from Enterococcusfaecalis. Microbiology 150:20692078.
96 Rich, R. L., B. Kreikemeyer, R. T. Owens, S. LaBrenz, S. V. Narayana, G. M. Weinstock, B. E. Murray and M. Hook. 1999. Ace is a collagen-binding MSCRAMM from Enterococcus faecalis. J. Biol. Chem. 274:2693926945.
97 Nallapareddy, S. R., X. Qin, G. M. Weinstock, M. Hook and B. E. Murray. 2000. Enterococcusfaecalis adhesin, ace, mediates attachment to extracellular matrix proteins collagen type IV and laminin as well as collagen type I. Infect. Immun. 68:5218-5224.
98 Nallapareddy, S. R., K. V. Singh, R. W. Duh, G. M. Weinstock and B. E. Murray.
2000. Diversity of ace, a gene encoding a microbial surface component recognizing adhesive matrix molecules, from different strains of Enterococcusfaecalis and evidence for production of ace during human infections. Infect. Immun. 68:5210-5217.
E. Gouin and P. Cossart. 1991. Entry of Listeria monocytogenes into cells is mediated by internalin, a repeat protein reminiscent of surface antigens from gram-positive cocci. Cell 65:1127-1141.
100 Mengaud, J., H. Ohayon, P. Gounon, R. M. Mege and P. Cossart. 1996. E-cad-herin is the receptor for internalin, a surface protein required for entry of
L. monocytogenes into epithelial cells. Cell 84:923-932.
101 Lecuit, M., S. Vandormael-Pournin, J. Lefort, M. Huerre, P. Gounon,
2001. A transgenic model for listeriosis: role of internalin in crossing the intestinal barrier. Science 292:1722-1725.
102 Jacquet, C., M. Doumith, J. I. Gordon, P. M. Martin, P. Cossart and M. Lecuit. 2004. A molecular marker for evaluating the pathogenic potential of food-borne Listeria monocytogenes. J. Infect. Dis. 189:2094-2100.
103 Reid, S. D., A. G. Montgomery, J. M. Voyich, F. R. DeLeo, B. Lei, R. M. Ireland, N. M. Green, M. Liu, S. Lukomski and J. M. Musser. 2003. Characterization of an extracellular virulence factor made by group A Streptococcus with homology to the Listeria monocytogenes internalin family ofproteins. Infect. Immun. 71:7043-7052.
104 Rakita, R. M., N. N. Vanek, K. Jacques-Palaz, M. Mee, M. M. Mariscalco, G. M. Dunny, M. Snuggs, W. B. Van Winkle and S. I. Simon. 1999. Enterococcus fae-calis bearing aggregation substance is resistant to killing by human neutrophils despite phagocytosis and neutrophil activation. Infect. Immun. 67:6067-6075.
105 Vanek, N. N., S. I. Simon, K. Jacques-Palaz, M. M. Mariscalco, G. M. Dunny and R. M. Rakita. 1999. Enterococcusfae-calis aggregation substance promotes opsonin-independent binding to human neutrophils via a complement receptor type 3-mediated mechanism. FEMS Immunol. Med. Microbiol. 26:49-60.
106 Kreft, B., R. Marre, U. Schramm and R. Wirth. 1992. Aggregation substance of Enterococcusfaecalis mediates adhesion to cultured renal tubular cells. Infect. Immun. 60:25-30.
107 Waters, C. M., H. Hirt, J. K. McCormick, P. M. Schlievert, C. L. Wells and G. M. Dunny. 2004. An amino-terminal domain of Enterococcus faecalis aggregation substance is required for aggregation, bacterial internalization by epithelial cells and binding to lipoteichoic acid. Mol. Microbiol. 52:1159-1171.
108 Wells, C. L., E. A. Moore, J. A. Hoag, H. Hirt, G. M. Dunny and S. L. Erland-sen. 2000. Inducible expression of Enter-ococcus faecalis aggregation substance surface protein facilitates bacterial inter-nalization by cultured enterocytes. Infect. Immun. 68:7190-7194.
109 Isenmann, R., M. Schwarz, E. Rozd-zinski, R. Marre and H. G. Beger. 2000. Aggregation substance promotes colo-nic mucosal invasion of Enterococcusfaecalis in an ex vivo model. J. Surg. Res. 89:132-138.
110 Olmsted, S. B., G. M. Dunny, S. L. Erlandsen and C. L. Wells. 1994. A plas-mid-encoded surface protein on Entero-coccus faecalis augments its internaliza-tion by cultured intestinal epithelial cells. J. Infect. Dis. 170:1549-1556.
C. Waters and G. Dunny. 2004. Entero-coccal aggregation substance and binding substance are not major contributors to urinary tract colonization by Enterococcus faecalis in a mouse model of ascending unobstructed urinary tract infection. Infect. Immun. 72:24452448.
112 Dramsi, S., F. Bourdichon, D. Cabanes, M. Lecuit, H. Fsihi and P. Cossart. 2004. FbpA, a novel multifunctional Listeria monocytogenes virulence factor. Mol. Microbiol. 53:639-649.
113 Shankar, V., A. S. Baghdayan, M. M. Huycke, G. Lindahl and M. S. Gilmore. 1999. Infection-derived Enterococcusfaecalis strains are enriched in esp, a gene encoding a novel surface protein. Infect. Immun. 67:193-200.
114 Shankar, N., C. V. Lockatell, A. S. Baghdayan, C. Drachenberg, M. S. Gilmore and D. E. Johnson. 2001. Role of Enterococcusfaecalis surface protein Esp in the pathogenesis of ascending urinary tract infection. Infect. Immun. 69:43664372.
115 Tendolkar, P. M., A. S. Baghdayan, M. S. Gilmore and N. Shankar. 2004. Entero-coccal surface protein, Esp, enhances biofilm formation by Enterococcusfaecalis. Infect. Immun. 72:6032-6039.
116 Kristich, C. J., Y. H. Li, D. G. Cvitkovitch and G. M. Dunny. 2004. Esp-indepen-dent biofilm formation by Enterococcus faecalis. J. Bacteriol. 186:154-163.
117 Hancock, L. E. and M. S. Gilmore. 2002. The capsular polysaccharide of Entero-coccus faecalis and its relationship to other polysaccharides in the cell wall. Proc. Natl. Acad. Sci. U. S.A. 99:15741579.
118 Hufnagel, M., L. E. Hancock, S. Koch, C. Theilacker, M. S. Gilmore and
J. Huebner. 2004. Serological and genetic diversity of capsular polysaccha-rides in Enterococcus faecalis. J. Clin. Microbiol. 42:2548-2557.
119 Zeng, J., F. Teng, G. M. Weinstock and B. E. Murray. 2004. Translocation of Enterococcus faecalis strains across a monolayer of polarized human entero-cyte-like T84 cells. J. Clin. Microbiol. 42:1149-1154.
E. Milohanic, F. Fiedler, P. Berche and P. Trieu-Cuot. 2002. Formation of D-alanyl-lipoteichoic acid is required for adhesion and virulence of Listeria monocytogenes. Mol. Microbiol. 43:1-14.
L. V. Collins, P. Staubitz, G. Nicholson, H. Kalbacher, W. F. Nieuwenhuizen, G. Jung, A. Tarkowski et al. 2001. Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with 1-lysine. J. Exp. Med. 193:1067-1076.
122 Dussurget, O., D. Cabanes, P. Dehoux, M. Lecuit, C. Buchrieser, P. Glaser and P. Cossart. 2002. Listeria monocytogenes bile salt hydrolase is a PrfA-regulated virulence factor involved in the intestinal and hepatic phases of listeriosis. Mol. Microbiol. 45:1095-1106.
123 Martinez, A. and R. Kolter. 1997. Protection of DNA during oxidative stress by the nonspecific DNA-binding protein Dps. J. Bacteriol. 179:5188-5194.
124 Altendorf,K., and W. Epstein. 1996. The Kdp-ATPase of Escherichia coli. In: Biomembranes. A. G. Lee, editor, vol. 5. JAI Press, Greenwich, Conn., 403-420.
125 Vimr, E. and C. Lichtensteiger. 2002.
To sialylate, or not to sialylate: that is the question. Trends Microbiol. 10:254-257.
126 Sandt, C. H., J. E. Hopper and C. W. Hill. 2002. Activation ofprophage eib genes for immunoglobulin-binding proteins by genes from the IbrAB genetic island of Escherichia coli ECOR-9. J. Bacteriol. 184:3640-3648.
127 Froseth, B. R., R. E. Herman and L. L. McKay. 1988. Cloning of nisin resistance determinant and replication origin on 7.6-kilobase EcoRI fragment of pNP40 from Streptococcus lactis subsp. diacetylactis DRC3. Appl. Environ. Microbiol. 54:2136-2139.
128 Froseth, B. R. and L. L. McKay. 1991. Molecular characterization ofthe nisin resistance region of Lactococcus lactis subsp. lactis biovar diacetylactis DRC3. Appl. Environ. Microbiol. 57:804-811.
129 Jones, A. L., K. M. Knoll and C. E. Rubens. 2000. Identification of Streptococcus agalactiae virulence genes in the neonatal rat sepsis model using signature-tagged mutagenesis. Mol. Microbiol. 37:1444-1455.
Was this article helpful?