Virulence Plasmids of Nonsporulating Gram-Positive Pathogens

Chris M. Pillar; Michael S. Gilmore

doi:10.1128/9781555817732.ch21

Chapter 21 : Virulence Plasmids of Nonsporulating Gram-Positive Pathogens

Authors: Chris M. Pillar¹, Michael S. Gilmore²

VIEW AFFILIATIONS HIDE AFFILIATIONS

Affiliations: 1: Department of Ophthalmology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190; 2: Departments of Microbiology and Immunology, and Ophthalmology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190

Content Type: Monograph

Publication Year: 2004

Category: Microbial Genetics and Molecular Biology

Book DOI: 10.1128/9781555817732

Chapter DOI: 10.1128/9781555817732.ch21

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:

Virulence Plasmids of Nonsporulating Gram-Positive Pathogens, Page 1 of 2

< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555817732/9781555812652_Chap21-1.gif /docserver/preview/fulltext/10.1128/9781555817732/9781555812652_Chap21-2.gif

Abstract:

Gram-positive bacteria are leading causes of many types of human infection, including pneumonia; skin and nasopharyngeal infections; and, among hospitalized patients, bloodstream, urinary tract, and surgical wound infections. As variable traits of the species, many of these virulence properties are encoded by mobile genetic elements, such as virulence plasmids and pathogenicity islands. This chapter reviews virulence plasmids in nonsporulating gram-positive bacteria and examines their contribution to the pathogenesis of disease. More recent studies have determined the nature of the bacteriocin activity linked with exfoliative toxin B (ETB) virulence plasmids. Some Enterococcus faecalis strains produce a cytolysin with both bactericidal and toxin activity against eukaryotic cells. The cytolysin operon occurs along with aggregation substance on pheromone-responsive plasmids and within the recently described 150-kb pathogenicity island on which enterococcal surface protein (Esp) and aggregation substance are found. Aggregation substance expression has also been shown to correlate with an enhanced uptake of enterococci by intestinal epithelial cells. However, this increase in uptake did not result in an increase in translocation across intestinal epithelium in vitro. Virulence plasmids may then represent "selfish DNA" of limited benefit to the bacterium that takes advantage of an otherwise stable, intimate association to ensure its perpetuation, with selection limiting its presence to a small proportion of the population so as not to jeopardize the commensal existence of the vast majority.

Citation: Pillar C, Gilmore M. 2004. Virulence Plasmids of Nonsporulating Gram-Positive Pathogens, p 439-454. In Funnell B, Phillips G (ed), Plasmid Biology. ASM Press, Washington, DC. doi: 10.1128/9781555817732.ch21

Key Concept Ranking

Mobile Genetic Elements: 0.6988185
Toxic Shock Syndrome: 0.4367659
Urinary Tract Infections: 0.42768192

0.6988185

Highlighted Text: Show | Hide

Full text loading...

Figures

Virulence Plasmids of Nonsporulating Gram-Positive Pathogens

[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555817732.chap21-1,webId=/content/author/10.1128/9781555817732.chap21-1,properties={foaf_givenname=Chris M., foaf_name=Chris M. Pillar, foaf_surname=Pillar, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555817732.chap21-aff1]]}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555817732.chap21-2,webId=/content/author/10.1128/9781555817732.chap21-2,properties={foaf_givenname=Michael S., foaf_name=Michael S. Gilmore, foaf_surname=Gilmore, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555817732.chap21-aff2]]}]]

/content/10.1128/9781555817732.chap21.fig21-1

Figure 1

Restriction map of pIB485 encoding SED and SEJ. Genes encoding cadmium resistance (cad) and resistance to beta-lactams (bla) are also indicated. Plasmid diagram contributed by J. J. landolo, Oklahoma University Health Sciences Center (OUHSC), Oklahoma City, Okla.

10.1128/9781555817732/fig21-1_thmb.gif

10.1128/9781555817732/fig21-1.gif

Figure 1

/content/10.1128/9781555817732.chap21.fig21-2

Figure 2

Plasmid map of a representative ETB-expressing plasmid, pETB. ORFs encoding ETB, cadmium resistance (cad), an operon responsible for production of staphylococcin c55 (bacteriocin operon), and the virulence factor EDIN-C are depicted (accession no. NC_003265) (174).

10.1128/9781555817732/fig21-2_thmb.gif

10.1128/9781555817732/fig21-2.gif

Figure 2

/content/10.1128/9781555817732.chap21.fig21-3

Figure 3

(A) Plasmid map of pADl depicting UV-resistance genes (uvr), the cytolysin operon, and genes involved in plasmid maintenance/transmission ( 46 , 56 ). (B) Depiction of genes involved in plasmid transfer and pheromone-sensing (adapted from reference 162 ). (C) Regulation of pheromone-response-mediated plasmid transfer; transcripts are depicted by arrows (adapted from reference 22 ).

10.1128/9781555817732/fig21-3_thmb.gif

10.1128/9781555817732/fig21-3.gif

Figure 3

/content/10.1128/9781555817732.chap21.fig21-4

Figure 4

(A) Detailed schematic of cytolysin operon (contributed by W. Haas, OUHSC, Oklahoma City, Okla.). (B) Schematic of cytolysin expression and posttranslational modification. ( 1 ) CyILL and CylLS, are synthesized, ( 2 ) arc intracellulary modified by CylM to create CylLL * and CylLS,* ( 3 ) arc secreted and further modified by CylB, resulting in CyILL′ and CylLS ′ and ( 4 ) are cleaved extracellularly by CylA to form the active cytolysin components CylLL″ and CylLS″. CylLL″ and CylLS″ are capable of forming aggregates ( 5 ) but are prevented from lysing cytolysin expressing cells via Cyl ( 6 ) (contributed by W. Haas, OUHSC, Oklahoma City, Okla.).

10.1128/9781555817732/fig21-4_thmb.gif

10.1128/9781555817732/fig21-4.gif

Figure 4

/content/10.1128/9781555817732.chap21.fig21-5

Figure 5

Plasmid map of virulence plasmid p33701 of R. equi. ORFs believed to be involved in plasmid maintenance and conjugation are depicted in gray, ORFs encoding Vaps are depicted in black, and putative ORFs within the proposed pathogenicity island are depicted in white ( 148 ).

10.1128/9781555817732/fig21-5_thmb.gif

10.1128/9781555817732/fig21-5.gif

Figure 5

References

/content/book/10.1128/9781555817732.chap21

1. Adesiyun, A. A.,, W. Lenz,, and K. P. Schaal. 1991. Exfoliative toxin production by Staphylococcus aureus strains isolated from animals and human beings in Nigeria. Microbiologica 14: 357– 362.

2. Aktories, K. 1997. Rho proteins: targets for bacterial toxins. Trends Microbiol. 5: 282– 288.

3. Altboum, Z.,, I. Hertman,, and S. Sarid. 1985. Penicillinase plasmid-linked genetic determinants for enterotoxins B and CI production in Staphylococcus aureus. Infect. Immun. 47: 514– 521.

4. Amagai, M.,, N. Matsuyoshi,, Z. H. Wang,, C. Andl,, and J. R. Stanley. 2000. Toxin in bullous impetigo and staphylococcal scalded-skin syndrome targets desmoglein 1. Nat. Med. 6: 1275– 1277.

5. An, F. Y.,, and D. B. Clewell. 1994. Characterization of the determinant (traB) encoding sex pheromone shutdown by the hemolysin/bacteriocin plasmid pAD1 in Enterococcus faecalis. Plasmid 31: 215– 221.

6. Arbuthnott, J. P.,, J. Kent,, A. Lyell, and C G. Gemmell. 1971. Toxic epidermal necrolysis produced by an extracellular product of Staphylococcus aureus. Br. J. Dermatol. 85: 145– 149.

7. Balaban, N.,, and A. Rasooly. 2000. Staphylococcal enterotoxins. Int. J. Food Microbiol. 61: 1– 10.

8. Banerjee, S.,, and J. N. Hansen. 1988. Structure and expression of a gene encoding the precursor of subtilin, a small protein antibiotic. J. Biol. Chem. 263: 9508– 9514.

9. Bayles, K. W.,, and J. J. landolo. 1989. Genetic and molecular analyses of the gene encoding staphylococcal enterotoxin D. J. Bacteriol. 171: 4799– 4806.

10. Bensing, B. A.,, and G. M. Dunny. 1993. Cloning and molecular analysis of genes affecting expression of binding substance, the recipient-encoded receptor(s) mediating mating aggregate formation in Enterococcus faecalis. J. Bacteriol. 175: 7421– 7429.

11. Bergdoll, M. S.,, J . K. Czop,, and S. S. Gould. 1974. Enterotoxin synthesis by the staphylococci. Ann. N. Y. Acad. Sci. 236: 307– 316.

12. Berti, M.,, G. Candiani,, A. Kaufhold,, A. Muscholl,, and R. Wirth. 1998. Docs aggregation substance of Enterococcus faecalis contribute to development of endocarditis? Infection 26: 48– 53.

13. Bohach, G. A.,, and P. M. Sclilievert. 1987. Expression of staphylococcal enterotoxin C1 in Escherichia coli. Infect. Immun. 55: 428– 432.

14. Booth, M. CM C. P. Bogie, H. G. Sahl, R. J. Siezen, K. L. Hatter, and M. S. Gilmore. 1996. Structural analysis and proteolytic activation of Enterococcus faecalis cytolysin, a novel lantibiotic. Mol. Microbiol. 21: 1175– 1184.

15. Booth, M. C., L. M. Pence,, P. Mahasreshti,, M. C. Callegan,, and M. S. Gilmore. 2001. Clonal associations among Staphylococcus aureus isolates from various sites of infection. Infect. Immun. 69: 345– 352.

16. Brock, T.,, B. Peachcr,, and D. Pierson. 1963. Survey of the bacteriocines of enterococci. J. Bacteriol. 86: 702– 707.

17. Byrne, B. A.,, J. F. Prescott,, G. H. Palmer,, S. Takai,, V. M. Nicholson,, D. C. Alperin,, and S. A. Hines. 2001. Virulence plasmid of Rhodococcus equi contains inducible gene family encoding secreted proteins. Infect. Immun. 69: 650– 656.

18. Casman, E. P. 1965. Staphylococcal enterotoxin. Ann. N. V. Acad. Sci. 128: 124– 131.

19. Chintagumpala, M. M.,, J. A. Mollick,, and R. R. Rich. 1991. Staphylococcal toxins bind to different sites on HLA-DR. J. Immunol. 147: 3876– 3881.

20. Choi, Y. W.,, A. Herman,, D. DiGiusto,, T. Wade,, P. Marrack,, and J. Kapplcr. 1990. Residues of the variable region of the T-cell-receptor beta-chain that interact with S. aureus toxin superantigens. Nature 346: 471– 473.

21. Chow, J. W.,, L. A. Thai,, 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 Cbemother. 37: 2474– 247.

22. Clewell, D., 1999. Sex pheromone systems in enterococci, p. 47– 65. In G. Dunny, and S. Winans (ed.), Cell-Cell Signaling in Bacteria. American Society for Microbiology, Washington, D.C..

23. Clewell, D.,, Y. Yagi,, Y. Ike,, R. Craig,, B. Brown,, and F. An,. 1982. S ex pheromones in Streptococcus faecalis: multiple pheromone systems in strain DS5, similarities of pAD1 and pAMdl,and mutants of pAD1 altered in conjugative properties, p. 97– 100. In D. Schlessinger (ed.), Microbiology—1982. American Society for Microbiology, Washington, D.C..

24. Clewell, D. B. 1993. Bacterial sex pheromone-induced plasmid transfer. Cell 73: 9– 12.

25. Clewell, D. B. 1981. Plasmids, drug resistance, and gene transfer in the genus Streptococcus. Microbiol. Rev. 45: 409– 436.

26. Clewell, D. B.,, P. K. Tomich,, M. C Gawron-Burke,, A. E. Franke,, Y. Yagi,, and F. Y. An. 1982. Mapping of Streptococcus faecalis plasmids pADl and pAD2 and studies relating to transposition of Tn 917 J . Bacteriol. 152: 1220– 1230.

27. Coburn, P. S.,, L. E. Hancock,, M. C. Booth,, and M. S. Gilmore. 1999. A novel means of self-protection, unrelated to toxin activation, confers immunity to the bactericidal effects of the Enterococcus faecalis cytolysin. Infect. Immun. 67: 3339– 3347.

28. Colmar, I.,, and T. Horaud. 1987. Enterococcus faecalis hemolysin-bacteriocin plasmids belong to the same incompatibility group. Appl. Environ. Microbiol. 53: 567– 570.

29. Crupper, S. S.,, A. J. Gies,, and J. J. landolo. 1997. Purification and characterization of staphylococcin BacR1, a broad-spectrum bacteriocin. Appl. Environ. Microbiol. 63: 4185– 4190.

30. Dajani, A. S. 1972. The scalded-skin syndrome: relation to phage-group II staphylococci. J. Infect. Dis. 125: 548– 551.

31. Dancer, S. J.,, R. Garratt,, J. Saldanha,, H. Jhoti,, and R. Evans. 1990. The epidermolytic toxins are serine proteases. EEBS Lett. 268: 129– 132.

32. Dancer, S. J.,, and W. C Noble. 1991. Nasal, axillary, and perineal carriage of Staphylococcus aureus among women: identification of strains producing epidermolytic toxin, J. Clin. Pathol. 44: 681– 684.

33. Davies, J.. 1994. Inactivation of antibiotics and the dissemination of resistance genes. Science 264: 375– 382.

34. de Azavedo, J.,, and J. P. Arbuthnott. 1981. Prevalence of epidermolytic toxin in clinical isolates of Staphylococcus aureus .J. Med. Microbiol. 14: 341– 344.

35. Doolittle, W. F.,, and C. Sapienza. 1980. Selfish genes, the phenotype paradigm and genome evolution. Nature 284: 601– 603.

36. Dorman, C. J.,, and M. E. Porter. 1998. The Shigella virulence gene regulatory cascade: a paradigm of bacterial gene control mechanisms. Mol. Microbiol. 29: 677– 684.

37. Dunny, G. M.,, and D. B. Clewell. 1975. Transmissible toxin (hemolysin) plasmid in Streptococcus faecalis and its mobilization of a noninfectious drug resistance plasmid. J. Bacteriol. 124: 784– 790.

38. Dunny, G.,, M. R. A. Craig,, R. L. Carron,, and D. B. Clewell. 1979. Plasmid transfer in Streptococcus faecalis: production of multiple sex pheromones by recipients. Plasmid 2: 454– 465.

39. Dunny, G. M.,, B. A. Leonard,, and P. J. Hedberg. 1995. Pheromone-inducible conjugation in Enterococcus faecalis: interbacterial and host-parasite chemical communication. J. Bacteriol. 177: 871– 876.

40. Dupont, H.,, P. Montravers,, J. Mohler,, and C. Carbon. 1998. Disparate findings on the role of virulence factors of Enterococcus faecalis in mouse and rat models of peritonitis. Infect. Immun. 66: 2570– 2575.

41. Ehrenfeld, E. E.,, R. E. Kesslcr,, and D. B. Clewell. 1986. Identification of pheromone-induced surface proteins in Streptococcus faecalis and evidence of a role for lipoteichoic acid in formation of mating aggregates. J. Bacteriol. 168: 6– 12.

42. Elias, P. M.,, P. Fritsch,, G. Tappeiner,, H. Mittermayer,, and K. Wolff. 1974. Experimental staphylococcal toxic epidermal necrolysis (TEN) in adult humans and mice. J. Lab. Clin. Med. 84: 414– 424.

43. Flahaut, S.,, J. Frere,, P. Boutibonnes,, and Y. Auffray. 1996. Comparison of the bile salts and sodium dodecyl sulfate stress responses in Enterococcus faecalis. Appl. Environ. Microbiol. 62: 2416– 2420.

44. Flahaut, S.,, A. Hartke,, J. C. Giard,, and Y. Auffray. 1997. Alkaline stress response in Enterococcus faecalis: adaptation, cross-protection, and changes in protein synthesis. Appl. Environ. Microbiol. 63: 812– 814.

45. Flahaut, S.,, A. Hartke,, J. C. Giard,, A. Benachour,, P. Boutibonnes,, and Y. Auffray. 1996. Relationship between stress response toward bile salts, acid and heat treatment in Enterococcus faecalis. FEMS Microbiol. Lett. 138: 49– 54.

46. Francia, M. V.,, W. Haas,, R. Wirth,, 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 plasmid pAD1 and identification of a second transfer origin. Plasmid 46: 117– 127.

47. Galli, D.,, F. Lottspeich,, and R. Wirth. 1990. Sequence analysis of Enterococcus faecalis aggregation substance encoded by the sex pheromone plasmid pAD1 Mol. Microbiol. 4: 895– 904.

48. Galli, D.,, R. Wirth,, and G. Wanner. 1989. Identification of aggregation substances of Enterococcus faecalis cells after induction by sex pheromones. An immunological and ultra-structural investigation. Arch. Microbiol. 151: 486– 490.

49. 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. USA 98: 10892– 10897.

50. Giguere, S.,, M. K. Hondalus,, J. A. Yager,, P. Darrah,, D. M. Mosser,, and J. F. Prescott. 1999. Role of the 85-kilobase plasmid and plasmid-encoded virulence-associated protein A in intracellular survival and virulence of Rhodococcus equi. Infect. Immun. 67: 3548– 3557.

51. Gilmore, M. S.,, P. S. Coburn,, S. R. Nallapareddy,, and B. E. Murray,. 2002. Enterococcal virulence, p. 301– 354. In M. S. Gilmore (ed.), The Enterococci. Pathogenesis, Molecular Biology, and Antimicrobial Resistance. American Society for Microbiology, Washington, D.C..

52. Gilmore, M. S.,, R. A. Segarra,, and M. C. Booth. 1990. An HlyB-type function is required for expression of the Enterococcus faecalis hemolysin/bacteriocin. Infect. Immun. 58: 3914– 3923.

53. Gilmore, M. S.,, R. A. Segarra,, M. C, Booth, C. P. Bogie, L. R. Hall, and D. B. Clewell. 1994. Genetic structure of the Enterococcus faecalis plasmid pAD1-encoded cytolytic toxin system and its relationship to lantibiotic determinants. J. Bacteriol. 176: 7335– 7344.

54. Gomez-Lus, R. 1998. Evolution of bacterial resistance to antibiotics during the last three decades. Int. Microbiol 1: 279– 284.

55. Gutschik, E.,, S. Moller,, and N. Christensen. 1979. Experimental endocarditis in rabbits. 3. Significance of the proteolytic capacity of the infecting strains of Streptococcus faecalis. Acta Pathol. Microbiol. Scand. Sect. B 87: 353– 362.

56. Haas, W.,, and M. S. Gilmore. 1999. Molecular nature of a novel bacterial toxin; the cytolysin of Enterococcus faecalis. Med. Microbiol. Immunol. (Berlin) 187: 183– 190.

57. Haas, W.,, B. D. Shepard,, and M. S. Gilmore. 2002. Two-component regulator of Enterococcus faecalis cytolysin responds to quorum-sensing autoinduction. Nature 415: 84– 87.

58. Hancock, L. E.,, and M. S. Gilmore. 2002. The capsular polysaccharide of Enterococcus faecalis and its relationship to other polysaccharides in the cell wall. Proc. Natl. Acad. Sci. USA 99: 1574– 1579.

59. Hancock, L., E. and M. S. Gilmore. 1999. Enterococcal pathogenicity, p. 251– 258 . In V. Fischetti,, R. Novick,, J. Ferretti,, D. Portnoy,, and J. Rood (ed.), Gram-Positive Pathogens. American Society for Microbiology, Washington, D.C..

60. Hirt, H.,, P. M. Schlievert,, and G. M. Dunny. 2002. In vivo induction of virulence and antibiotic resistance transfer in Enterococcus faecalis mediated by the sex pheromone-sensing system of pCF10. Infect. Immun. 70: 716– 723.

61. Hirt, H.,, R. Wirth,, and A. Muscholl. 1996. Comparative analysis of 18 sex pheromone plasmids from Enterococcus faecalis: detection of a new insertion element on pPD1 and implications for the evolution of this plasmid family. Mol Gen. Genet. 252: 640– 647.

62. Holmberg, S. D.,, and P. A. Blake. 1984. Staphylococcal food poisoning in the United States. New facts and old misconceptions. JAMA 251: 487– 489.

63. 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.

64. Huycke, M. M.,, and M. S. Gilmore. 1995. Frequency of aggregation substance and cytolysin genes among enterococcal endocarditis isolates. Plasmid 34: 152– 156.

65. Huycke, M. M.,, M. S. Gilmore,, B. D. Jett,, and J. L. Booth. 1992. Transfer of pheromone-inducible plasmids between Enterococcus faecalis in the Syrian hamster gastrointestinal tract J. Infect. Dis. 166: 1188– 1191.

66. Huycke, M. M.,, W. A. Joyce,, and M. S. Gilmore. 1995. Enterococcus faecalis cytolysin without effect on the intestinal growth of susceptible enterococci in mice.;. Infect. Dis. 172: 273– 276.

67. Huycke, M. M. D. Moore, W. Joyce, 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 quinol oxidases. Mol. Microbiol. 42: 729– 740.

68. Huycke, M. M.,, D. F. Sahm,, and M. S. Gilmore. 1998. Multiple-drug resistant enterococci: the nature of the problem and an agenda for the future. Emerg. Infect. Dis. 4: 239– 249.

69. Huycke, M. M.,, C. A. Spiegel,, and M. S. Gilmore. 1991. Bacteremia caused by hemolytic, high-level gentamicin-resistant Enterococcus faecalis. Antimicrob. Agents Chemother. 35: 1626– 1634.

70. Ike, Y.,, and D. B. Clewell. 1984. Genetic analysis of the pAD1 pheromone response in Streptococcus faecalis, using transposon Tn 917 as an insertional mutagen. J. Bacteriol 158: 777– 783.

71. Ike, Y.,, D. B. Clewell,, R. A. Segarra,, and M. S. Gilmore. 1990. Genetic analysis of the pAD1 hemolysin/bacteriocin determinant in Enterococcus faecalis: Tn 917 insertional mutagenesis and cloning. J. Bacteriol. 172: 155– 163.

72. 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.

73. Ike, Y.,, H. Hashimoto,, and D. B. Clewell. 1987. High incidence of hemolysin production by Enterococcus (Streptococcus) faecalis strains associated with human parenteral infections. J. Clin. Microbiol 25: 1524– 1528.

74. Inoue, S.,, M. Sugai,, Y. Murooka, S, Y. Paik, Y. M. Hong, H. Ohgai, and H. Suginaka. 1991. Molecular cloning and sequencing of the epidermal cell differentiation inhibitor gene from Staphylococcus aureus. Biochem. Biopbys. Res. Commun. 174: 459– 464.

75. Jackson, M. P.,, and J. J. landolo. 1986. Cloning and expres sion of the exfoliative toxin B gene from Staphylococcus aureus. J. Bacteriol. 166: 5745– 80.

76. Jackson, M. P.,, and J. J. landolo. 1986. Sequence of the exfoliative toxin B gene of Staphylococcus aureus. J. Bacteriol 167: 726– 728.

77. Jacob, A. E.,, G. J. Douglas,, and S. J. Hobbs. 1975. Self-transferable plasmids determining the hemolysin and bacteriocin of Streptococcus faecalis var. zymogenes. J. Bacteriol 121: 863– 872.

78. Jett, B. D. R. V. Atkuri, and M. S. Gilmore. 1998. Enterococcus faecalis localization in experimental endophthalmitis: role of plasmid-encoded aggregation substance. Infect Immun. 66: 843– 848.

79. Jett, B. D.,, and M. S. Gilmore. 1990. The growth-inhibitory effect of the Enterococcus faecalis bacteriocin encoded by pAD1 extends to the oral streptococci. J. Dent. Res. 69: 1640– 1645.

80. Jett, B. D.,, M. M. Huycke,, and M. S. Gilmore. 1994. Virulence of enterococci. Clin. Microbiol. Rev. 7: 462– 478.

81. 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 F,nterococcus faecalis endophthalmitis. Infect. Immun. 60: 2445– 2452.

82. Kaletta, C.,, and K. D. Entian. 1989. Nisin, a peptide antibiotic: cloning and sequencing of the nisA gene and posttranslational processing of its peptide product. J. Bacteriol 171: 1597– 1601.

83. Kapral, F. A. 1974. Staphylococcus aureus: some host-parasite interactions, Ann. N. Y. Acad. Sci. 236: 267– 276.

84. Kondo, I.,, S. Sakurai,, and Y. Sarai. 1973. Purification of exfoliatin produced by Staphylococcus aureus of bacterio-phage group 2 and its physicochemical properties. Infect. Immun. 8: 156– 164.

85. Kondo, L.,, S. Sakurai,, Y. Sarai,, and S. Futaki. 1975. Two serotypes of exfoliatin and their distribution in staphylococcal strains isolated from patients with scalded skin syndrome. J. Clin. Microbiol. 1: 3974– 400.

86. Kornblum, J.,, B. N. Krciswirth,, S. J. Projan,, H. Ross,, and R. P. Novick,, 1991. Agn A polycistronic locus regulating exoprotein synthesis in Staphylococcus aureus, p. 3734– 02. In R. P. Novick (ed.), Molecular Biology of the Staphylococci. VCH Publishers, New York, N.Y..

87. Kreft, B.,, R. Marre,, U. Schramm,, and R. Wirth. 1992. Aggregation substance of Enterococcus faecalis mediates adhesion to cultured renal tubular cells. Infect. Immun. 60: 25– 30.

88. Ladhani, S.,, C. L. Joannou,, D. P. Lochrie,, R. W. Evans,, and S. M. Poston, 1999. Clinical, microbial, and biochemical aspects of the exfoliative toxins causing staphylococcal scalded-skin syndrome. Clin. Microbiol. Rev. 12: 224– 242.

89. Le Bouguenec, C.,, G. de Cespedes,, and T. Horaud. 1988. Molecular analysis of a composite chromosomal conjugative element (TnMOl) of Streptococcus pyogenes. J. Bacteriol 170: 3930– 3936.

90. Lee, C. Y.,, J. J. Schmidt,, A. D. Johnson-Winegar,, L. Spero,, and J. J. landolo. 1987. Sequence determination and comparison of the exfoliative toxin A and toxin B genes from Staphylococcus aureus. J. Bacteriol. 169: 3904– 3909.

91. Lindler, L. E.,, G. V. Piano,, V. Burland,, G. F. Mayhew,, and F. R. Blattner. 1998. Complete DNA sequence and detailed analysis of the Yersinia pestis KIM5 plasmid encoding murine toxin and capsular antigen. Infect. Immun. 66: 5731– 5742.

92. Lowney, E. D.,, J. V. Baublis,, G. M. Kreye,, E. R. Harrell,, and A. R. McKenzie. 1967. The scalded skin syndrome in small children. Arch. Dermatol. 95: 359– 369.

93. Mackawa, S.,, M. Yoshioka,,and Y. Kumamoto. 1992. Proposal of a new scheme for the serological typing of Enterococcus facialis strains. Microbiol. Immunol. 36: 671– 681.

94. McLay, A. L.,, J. P. Arbuthnott,, and A. LyelL. 1975. Action of staphylococcal epidermolytic toxin on mouse skin: an electron microscopic study. J . Invest. Dermatol. 65: 423– 428.

95. Melish, M. E.,, and L. A, Glasgow. 1971. Staphylococcal scalded skin syndrome: the expanded clinical syndrome. J. Pediatr. 78: 958– 967.

96. Melish, M. E., and L. A. Glasgow. 1970. The staphylococcal scalded-skin syndrome. N. Engl. J. Med. 282: 1114– 1119.

97. Melish, M. E.,, L. A. Glasgow,, and M. D. Turner. 1972. The staphylococcal scalded-skin syndrome: isolation and partial characterization of the exfoliative toxin. J. Infect. Dis. 125: 129– 140.

98. Melish, M. E.,, L. A. Glasgow,, M. D. Turner,, and C. B. Lillibridge. 1974. The staphylococcal epidermolytic toxin: its isolation, characterization, and site of action. Ann. N. Y. Acad. Sci. 236: 317– 342.

99. Miller, M. M.,, and F. A. Kapral. 1972. Neutralization of Staphylococcus aureus exfoliatin by antibody. Infect. Immun. 6: 561– 563.

100. Moellering, R.,. 1995. Enterococcus species, Streptococcus bovis, and Leuconostac species, p. 1826– 1835. In G. Mandell,, J. Bennett,, and R. Dolin (ed.), Principles and Practices of Infectious Diseases, 4th ed. Churchill Livingston, New York, N.Y..

101. Mollick, J. A.,, M. Chintagumpala,, R. G. Cook,, and R. R. Rich. 1991. Staphylococcal exotoxin activation of T cells. Role of exotoxin-MHC class II binding affinity and class II isotype. J. Immunol. 146: 463– 468.

102. Monday, S. R.,, and G. A. Bohach,. 1999. Properties of Staphylococcus aureus enterotoxins and toxic shock syndrome toxin-1, p. 589– 610. In J. Alouf, and J. Freer (ed.), The Comprehensive Sourcebook of Bacterial Protein Toxins. Academic Press, London, United Kingdom.

103. Mori, M.,, Y. Sakagami,, M. Narita,, A. Isogai,, M. Fujino,, C. Kitada,, R. A. Craig,, D. B. Clewell,, and A. Suzuki. 1984. Isolation and structure of the bacterial sex pheromone, cAD1, that induces plasmid transfer in Streptococcus faecalis. FEBS Lett. 178: 97– 100.

104. Mori, M.,, H. Tanaka,, Y. Sakagami,, A. Isogai,, M. Fujino,, C. Kitada,, B. A. White,, F. Y. An,, D. B. Clewell,, and A. Suzuki. 1986. Isolation and structure of the Streptococcus faecalis sex pheromone, cAM373. FEBS Lett. 206: 69– 72.

105. Mundy, L. M.,, D. F. Sahm,, and M. Gilmore. 2000. Relationships between enterococcal virulence and antimicrobial resistance. Clin. Microbiol. Rev. 13: 513– 522.

106. Murono, K.,, K. Fujita,, and H. Yoshioka. 1988. Microbiologic characteristics of exfoliative toxin-producing Staphylococcus aureus. Pediatr. Infect. Dis. J. 7: 313– 315.

107. Murray, B. E. 1990. The life and times of the Enterococcus. Clin. Microbiol. Rev. 3: 46– 65.

108. Muscholl-Silberhorn, A. B. 2000. Pheromone-regulated expression of sex pheromone plasmid pAD1-encoded aggregation substance depends on at least six upstream genes and a Ws-acting, orientation-dependent factor. J. Bacteriol. 182: 3816– 3825.

109. Nallapareddy, S. R.,, X. Qin,, G. M. Weinstock,, M. Hook,, and B. E. Murray. 2000. Enterococcus faecalis adhesin, ace, mediates attachment to extracellular matrix proteins collagen type IV and hi min in as well as collagen type I. Infect. Immun. 68: 5218– 5224.

110. 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 Enterococcus faecalis and evidence for production of ace during human infections. Infect Immun. 68: 5210– 5217.

111. Navaratna, M. A.,, H. G. Sahl,, and J. R. Tagg. 1999. Identification of genes encoding two-component lantibiotic production in Staphylococcus aureus CSS and other phage group II S. aureus strains and demonstration of an association with the exfoliative toxin B gene. Infect. Immun. 67: 4268– 4271.

112. Neu, H. C. 1992. The crisis in antibiotic resistance. Science 257: 1064– 1073.

113. Novick, R. P., 2000. Pathogenicity factors and their regulation, p. 392– 407. In V. Fischetti,, R. Novick,, J. Ferretti,, D. Portnoy,, and J. Rood (ed.), Gram-Positive Pathogens. American Society for Microbiology, Washington, D.C..

114. Oliver, D. R., B. L. Brown,, and D. B. Clewell. 1977. Characterization of plasmids determining hemolysin and bacteriocin production in Streptococcus faecalis 5952. J. Bacteriol. 130: 948– 950.

115. Olmsted, S. B., G. M. Dunny,, S. L. Erlandsen,, and C. L. Wells. 1994. A plasmid-encoded surface protein on Enterococcus faecalis augments its internalization by cultured intestinal epithelial cells. J. Infect Dis. 170: 1549– 1556.

116. Perry, R. D.,, S. C. Straley,, J. D. Fetherston,, D. J. Rose,, J. Gregor,, and F. R. Blattner. 1998. DNA sequencing and analysis of the low-Ca2+-response plasmid pCD1 of Yersinia pestis KIM5. Infect Immun. 66: 4611– 4623.

117. Piemont, Y., 1999. Staphylococcal epidermolytic toxins: structure, biological and pathophysiological properties, p. 657– 668. In J. Alouf, and J. Freer (ed.), The Comprehensive Sourcebook of Bacterial Protein Toxins. Academic Press, London, United Kingdom.

118. Piemont, Y.,, D. Rasoamananjara,, J. M. Fouace,, and T. Bruce. 1984. Epidemiological investigation of exfoliative toxin-producing Staphylococcus aureus strains in hospitalized patients. J. Clin. Microbiol. 19: 417– 420.

119. Projan, S. J.,, and R. P. Novick,. 1997. The molecular basis of virulence, p. 55– 81. In G. Archer, and K. Crossley (ed.), Staphylococci in Human Disease. Churchill Livingstone, New York, N.Y..

120. Qin, X.,, K. V. Singh,, G. M. Weinstock, and B, E. Murray. 2000. Effects of Enterococctts faecalis fsr genes on production of gelatinase and a serine protease and virulence. Infect. Immun. 68: 2579– 2586.

121. 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 faecalis bearing aggregation substance is resistant to killing by human neutrophils despite phagocytosis and neutrophil activation. Infect Immun. 67: 6067– 6075.

122. Richards, M. J.,, J. R. Edwards,, D. H. Culver,, and R. P. Gaynes. 2000. Nosocomial infections in combined medical-surgical intensive care units in the United States. Infect. Control Hosp. Epidemiol. 21: 510– 515.

123. Richards, M. J.,, J. R. Edwards,, D. H. Culver,, and R. P. Gaynes. 1999. Nosocomial infections in medical intensive care units in the United States. National Nosocomial Infections Surveillance System. Crit. Care Med. 27: 887– 892.

124. Rogolsky, M.,, R. Warren,, B. B. Wiley,, H. T. Nakamura,, and L. A. Glasgow. 1974. Nature of the genetic determinant controlling exfoliative toxin production in Staphylococcus aureus. J. Bacteriol. 117: 157– 165.

125. Rogolsky, M.,, and B. B. Wiley. 1977. Production and properties of a staphylococci genetically controlled by the staphylococcal plasmid for exfoliative toxin synthesis. Infect. Immun. 15: 726– 732.

126. Rowe-Magnus, D. A.,, and D. Mazel. 2001. Integrons: natural tools for bacterial genome evolution. Curr. Opin. Microbiol. 4: 565– 569.

127. Sannomiya, P.,, R. A. Craig,, D. B. Clewell,, A. Suzuki,, M. Fujino,, G. O. Till,, and W. A. Marasco. 1990. Characterization of a class of nonformylated Enterococcus faecalisderived neutrophil chemotactic peptides: the sex pheromones. Proc. Natl. Acad. Sci. USA 87: 66– 70.

128. Sato, H.,, Y. Matsumori, T, Tanabe, H. Saito, A. Shimizu, and J. Kawano. 1994. A new type of staphylococcal exfoliative toxin from a Staphylococcus aureus strain isolated from a horse with phlegmon. Infect Immun. 62: 3780– 3785.

129. Sato, H.,, T. Tanabe,, M. Kuramoto,, K. Tanaka,, T. Hashimoto,, and H. Saito. 1991. Isolation of exfoliative toxin from Staphylococcus hyicus subsp. hyicus and its exfoliative activity in the piglet. Vet. Microbiol. 27: 263– 275.

130. Sato, H.,, T. Watanabe,, Y. Murata,, A. Ohtake,, M. Nakamura,, C. Aizawa,, H. Saito,, and N. Machara. 1999. New exfoliative toxin produced by a plasmid-carrying strain of Staphylococcus hyicus. Infect. Immun. 67: 4014– 4018.

131. Schlievert, P. M.,, P. J. Gahr,, A. P. Assimacopoulos,, M. M. Dinges,, J. A. Stoehr,, J. W. Harmala,, H. Hirt,, and G. M. Dunny. 1998. Aggregation and binding substances enhance pathogenicity in rabbit models of Enterococcus faecalis endocarditis. Infect. Immun. 66: 218– 223.

132. Schnell, N.,, K. D. Entian,, U. Schneider,, F. Gotz,, H. Zahner,, R. Kellner,, and G. Jung. 1988. Prepeptide sequence of epidermin, a ribosomally synthesized antibiotic with four sulphide-rings. Nature 333: 276– 278.

133. Segarra, R. A.,, M. C. Booth,, D. A. Morales,, M. M. Huyeke,, and M. S. Gilmore. 1991. Molecular characterization of the Enterococcus faecalis cytolysin activator. Infect. Immun. 59: 1239– 1246.

134. Shafer, W. M.,, and J. J. landolo. 1978. Chromosomal locus for staphylococcal enterotoxin B. Infect. Immun. 20: 273– 278.

135. Shankar, N.,, A. S. Baghdayan,, and M. S. Gilmore. 2002. Modulation of virulence within a pathogenicity island in vancomycin-resistant Enterococcus faecalis. Nature 417: 746– 750.

136. Shankar, N. C.,, V. Lockatell,, A. S. Baghdayan,, C. Drachenberg,, M. S. Gilmore,, and D. E. Johnson. 2001. Role of Enterococcus faecalis surface protein Esp in the pathogenesis of ascending urinary tract infection. Infect. Immun. 69: 4366– 4372.

137. Sherwood, N.,, B. Russell,, A. Jay,, and K. Bowman. 1949. Studies on streptococci. III. New antibiotic substances produced by beta hemolytic streptococci. J. Infect. Dis. 84: 88– 91.

138. Singh, K. V.,, X. Qin,, G. M. Weinstock,, and B. E. Murray. 1998. Generation and testing of mutants of Enterococcus faecalis in a mouse peritonitis model. J . Infect. Dis. 178: 1416– 1420.

139. Skurray, R. A.,, and N. Firth, 1997. Molecular evolution of multiply-antibiotic-resistant staphylococci. Ciba Pound. Symp. 207: 167– 183; discussion 183– 191.

140. Stark, J. 1960. Antibiotic activity of haemolytic enterococci. Lancet i: 733– 734.

141. Stevens, S. X.,, H. G. Jensen,, B. D. Jett,, and M. S. Gilmore. 1992. A hemolysin-encoding plasmid contributes to bacterial virulence in experimental Enterococcus faecalis endophthalmitis. Invest. Ophthalmol. Vis. Sci. 33: 1650– 1656.

142. Su, Y. A.,, M. C. Sulavik,, P. He,, K. K. Makinen,, P. L. Makinen,, S. Fiedler,, R. Wirth,, and D. B. Clewell. 1991. Nucleotide sequence of the gelatinase gene (gelE) from Enterococcus faecalis subsp. liquefaciens. Infect. Immun. 59: 415– 420.

143. Sugai, M.,, T. Enomoto,, K. Hashimoto,, K. Matsumoto,, Y. Matsuo,, H. Ohgai,, Y. M. Hong,, S. Inoue,, K. Yoshikawa,, and H. Suginaka. 1990. A novel epidermal cell differentiation inhibitor (EDIN): purification and characterization from Staphylococcus aureus. Biochem. Biopbys. Res. Commun. 173: 92– 98.

144. Sussmuth, S. D.,, A. Muscholl-Silberhorn,, R. Wirth,, M. Susa,, R. Marre,, and E. Rozdzinski. 2000. Aggregation substance promotes adherence, phagocytosis, and intracellular survival of Enterococcus faecalis within human macrophages and suppresses respiratory burst. Infect. Immun. 68: 4900– 4906.

145. Takai, S.,, N. Fukunaga,, K. Kamisawa,, Y. Imai,, Y. Sasaki,, and S. Tsubaki. 1996. Expression of virulence-associated antigens of Rhodococcus equi is regulated by temperature and pH. Microbiol. Immunol. 40: 591– 594.

146. Takai, S.,, S. A. Hines,, T. Sekizaki,, V. M. Nicholson,, D. A. Alperin,, M. Osaki,, D. Takamatsu,, M. Nakamura,, K. Suzuki,, N. Ogino,, T. Kakuda,, H. Dan,, and J. F. Prescott. 2000. DNA sequence and comparison of virulence plasmids from Rhodococcus equi ATCC 33701 and 103. Infect. Immun. 68: 6840– 6847.

147. Takai, S.,, M. lie,, Y. Watanabe,, S. Tsubaki,, and T. Sckizaki. 1992. Virulence-associated 15- to 17-kilodalton antigens in Rhodococcus equh temperature-dependent expression and location of the antigens. Infect. Immun. 60: 2995– 2997.

148. Takai, S., Y, Imai, N. Fukunaga, Y. Uchida, K. Kamisawa, Y. Sasaki, S. Tsubaki, and T. Sckizaki. 1995. Identification of virulence-associated antigens and plasmids in Rhodococcus equi from patients with AIDS. J. Infect. Dis. 172: 1306– 1311.

149. Takai, S.,, K. Koike,, S. Ohbushi,, C. Izumi,, and S. Tsubaki. 1991. Identification of 15- to 17-kilodalton antigens associated with virulent Rhodococcus equi. J. Clin. Microbiol. 29: 439– 443.

150. Takai, S.,, T. Sckizaki,, T. Ozawa,, T. Sugawara,, Y. Watanabe,, and S. Tsubaki. 1991. Association between a large plasmid and 15- to 17-kilodalton antigens in virulent Rhodococcus equi. Infect. Immun. 59: 4056– 4060.

151. Takai, S.,, Y. Watanabe,, T. Ikeda,, T. Ozawa,, S. Matsukura,, Y. Tamada,, S. Tsubaki,, and T. Sckizaki. 1993. Virulence-associated plasmids in Rhodococcus equi. J. Clin. Microbiol. 31: 1726– 1729.

152. Tan, C.,, J. F. Prescott,, M. C. Patterson,, and V. M. Nicholson. 1995. Molecular characterization of a lipid-modified virulence-associated protein of Rhodococcus equi and its potential in protective immunity. Can. J. Vet. Res. 59: 51– 59.

153. Tanimoto, K.,, F. Y. An,, and D. B. Clewell. 1993. Characterization of the traC determinant of the Enterococcus faecalis hemolysin-bactcriocin plasmid pADl: binding of sex pheromone. J. Bacteriol. 175: 5260– 5264.

154. Tkachuk-Saad, O.,, and J . Prescott. 1991. Rhodococcus equi plasmids: isolation and partial characterization. J. Clin. Microbiol. 29: 2696– 2700.

155. Todd, E. 1934. A comparative serological study of streptolysins derived from human and from animal infections, with notes on pneumococcal hacmolysin, tetanolysin and staphylococcus toxin. J. Pathol. Bacteriol 39: 299– 321.

156. Todd, J. K. 1985. Staphylococcal toxin syndromes. Annu. Rev. Med. 36: 337– 347.

157. Toledo-Arana, A.,, J. Valle,, C. Solano,, M. J. Arrizubieta,, C. Cucarella,, M. Lamata,, B. Amorena,, J. Leiva,, J. R. Penades,, and I. Lasa. 2001. The enterococcal surface protein, Esp, is involved in Enterococcus faecalis biofilm formation. Appl. Environ. Microbiol. 67: 4538– 4545.

158. Tomich, P. K.,, F. Y. An,, S. P, Damle, and D. B. Clewell. 1979. Plasmid-related transmissibility and multiple drug resistance in Streptococcus faecalis subsp. zymogenes strain DS16, Antimicrob. Agents Chemother. 15: 828– 830.

159. Vanek, N. N.,, S. I. Simon,, K. Jacques-Palaz,, M. M. Mariscalco,, G. M. Dunny,, and R. M. Rakita. 1999. Enterococcus faecalis aggregation substance promotes opsonin-independent binding to human neutrophils via a complement receptor type 3-mediated mechanism. FEMS Immunol. Med. Microbiol. 26: 49– 60.

160. Warren, R.,, M. Rogolsky,, B. B. Wiley,, and L. A. Glasgow. 1974. Effect of ethidium bromide on elimination of exfoliative toxin and bacteriocin production in Staphylococcus aureus. J. Bacteriol. 118: 980– 985.

161. Warren, R. L. 1980. Exfoliative toxin plasmids of bacterio-phage group 2 Staphylococcus aureus: sequence homology. Infect. Immun. 30: 601– 606.

162. Weaver, K., 2000. Enterococcal genetics, p. 259– 271. In V. Fischetti,, R. Novick,, J. Ferretti,, D. Portnoy,, and J. Rood (ed.), Gram-Positive Pathogens. American Society for Microbiology, Washington, D.C..

163. Weaver, K. E.,, and D. B. Clewell. 1989. Construction of Enterococcus faecalis pAD1 miniplasmids: identification of a minimal pheromone response regulatory region and evaluation of a novel pheromone-dependent growth inhibition. Plasmid 22: 106– 119.

164. Weaver, K. E.,, D. B. Clewell,, and F. An. 1993. Identification, characterization, and nucleotide sequence of a region of Enterococcus faecalis pheromone-responsive plasmid pAD1 capable of autonomous replication. J. Bacteriol. 175: 1900– 1909.

165. Weaver, K. E.,, K. D. Jensen,, A. Colwell,, and S. I. Sriram. 1996. Functional analysis of the Enterococcus faecalis plasmid pAD1-encoded stability determinant par. Mol. Microbiol. 20: 53– 63.

166. Wells, C. L.,, R. P. Jechorek,, and S. L. Erlandsen. 1990. Evidence for the translocation of Enterococcus faecalis across the mouse intestinal tract. J Infect. Dis. 162: 82– 90.

167. Wieneke, A. A.,, D. Roberts,, and R. J. Gilbert. 1993. Staphylococcal food poisoning in the United Kingdom, 1969-90. Epidemiol. Infect. 110: 519– 531.

168. Wiley, B. B.,, L. A. Glasgow,, and M. Rogolsky. 1976. Staphylococcal scalded-skin syndrome: development of a primary binding assay for human antibody to the exfoliative toxin. Infect. Immun. 13: 513– 520.

169. Willems, R. J.,, W. Homan,, J. Top,, M. van Santen-Verheuvel,, D. Tribe,, X. Manzioros, C Gaillard, C. M. Vandenbroucke- Grauls, E. M. Mascini, E. van Kregten, J. D. van Embden, and M. J, Bonten. 2001. Variant esp gene as a marker of a distinct genetic lineage of vancomycin-resistant Enterococcus faecium spreading in hospitals. Lancet 357: 853– 855.

170.Wirth, R, 1994. The sex pheromone system of Enterococcus faecalis. More than just a plasmid-collection mechanism? Eur.J. Biochem. 222: 235– 246.

171. Woodford, N. 2001. Epidemiology of the genetic elements responsible for acquired glycopeptide resistance in enterococci. Microb. Drug Resist. 7: 229– 236.

172. Yager, J . A.,, C. A. Prescott,, D. P. Kramar,, H. Hannah,, G. A. Balson,, and B. A. Croy. 1991. The effect of experimental infection with Rhodococcus equi on immunodeficient mice. Vet. Microbiol. 28: 363– 376.

173. Yamaguchi, T.,, T. Hayashi,, H. Takami,, K. Nakasone,, M. Ohnishi,, K. Nakayama,, S. Yamada,, H. Komatsuzawa,, and M. Sugai. 2000. Phage conversion of exfoliative toxin A production in Staphylococcus aureus. Mol Microbiol. 38: 694– 705.

174. Yamaguchi, T.,, T. Hayashi,, H. Takami,, M. Ohnishi,, T. Murata,, K. Nakayama,, K. Asakawa,, M. Ohara,, H. Komatsuzawa,, and M. Sugai. 2001. Complete nucleotide sequence of a Staphylococcus aureus exfoliative toxin B plasmid and identification of a novel ADP-ribosykransfcrase, EDIN-C. Infect. Immun. 69: 7760– 7771.

175. Zhang, S. J. J. landolo, and G. C. Stewart. 1998. The enterotoxin D plasmid of Staphylococcus aureus encodes a second enterotoxin determinant (sej). FEMS Microbiol. Lett. 168: 227– 233.