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Seminars in Immunopathology

, Volume 34, Issue 2, pp 201–214 | Cite as

Molecular basis of Staphylococcus epidermidis infections

  • Michael Otto
Review

Abstract

Staphylococcus epidermidis is the most important member of the coagulase-negative staphylococci and one of the most abundant colonizers of human skin. While for a long time regarded as innocuous, it has been identified as the most frequent cause of device-related infections occurring in the hospital setting and is therefore now recognized as an important opportunistic pathogen. S. epidermidis produces a series of molecules that provide protection from host defenses. Specifically, many proteins and exopolymers, such as the exopolysaccharide PIA, contribute to biofilm formation and inhibit phagocytosis and the activity of human antimicrobial peptides. Furthermore, recent research has identified a family of pro-inflammatory peptides in S. epidermidis, the phenol-soluble modulins (PSMs), which have multiple functions in immune evasion and biofilm development, and may be cytolytic. However, in accordance with the relatively benign relationship that S. epidermidis has with its host, production of aggressive members of the PSM family is kept at a low level. Interestingly, in contrast to S. aureus with its large arsenal of toxins developed for causing infection in the human host, most if not all “virulence factors” of S. epidermidis appear to have original functions in the commensal lifestyle of this bacterium.

Keywords

Staphylococcus epidermidis Biofilm Phenol-soluble modulins Polysaccharide intercellular adhesin Device-related infections Hospital-associated infections 

Notes

Acknowledgments

This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

References

  1. 1.
    Kloos WE, Musselwhite MS (1975) Distribution and persistence of Staphylococcus and Micrococcus species and other aerobic bacteria on human skin. Appl Microbiol 30(3):381–385PubMedGoogle Scholar
  2. 2.
    Grice EA, Segre JA (2011) The skin microbiome. Nat Rev Microbiol 9(4):244–253. doi: 10.1038/nrmicro2537 PubMedGoogle Scholar
  3. 3.
    Kloos W, Schleifer KH (1986) Staphylococcus. In: Sneath PHA, Mair NS, Sharpe ME, Holt JG (eds) Bergey’s manual of systematic bacteriology. Williams & Wilkins, BaltimoreGoogle Scholar
  4. 4.
    Rogers KL, Fey PD, Rupp ME (2009) Coagulase-negative staphylococcal infections. Infect Dis Clin North Am 23(1):73–98PubMedGoogle Scholar
  5. 5.
    Etienne J, Pangon B, Leport C, Wolff M, Clair B, Perronne C, Brun Y, Bure A (1989) Staphylococcus lugdunensis endocarditis. Lancet 1(8634):390PubMedGoogle Scholar
  6. 6.
    Zinkernagel AS, Zinkernagel MS, Elzi MV, Genoni M, Gubler J, Zbinden R, Mueller NJ (2008) Significance of Staphylococcus lugdunensis bacteremia: report of 28 cases and review of the literature. Infection 36(4):314–321PubMedGoogle Scholar
  7. 7.
    Lina G, Etienne J, Vandenesch F (2000) Biology and pathogenicity of staphylococci other than Staphylococcus aureus and Staphylococcus epidermidis. In: Fischetti VA, Novick RP, Ferretti JJ, Portnoy DA, Rood JI (eds) Gram-positive pathogens. ASM, Washington, DCGoogle Scholar
  8. 8.
    O’Grady NP, Alexander M, Dellinger EP, Gerberding JL, Heard SO, Maki DG, Masur H, McCormick RD, Mermel LA, Pearson ML, Raad II, Randolph A, Weinstein RA (2002) Guidelines for the prevention of intravascular catheter-related infections. Centers for Disease Control and Prevention. MMWR Recomm Rep 51(RR-10):1–29PubMedGoogle Scholar
  9. 9.
    Raad I, Hanna H, Maki D (2007) Intravascular catheter-related infections: advances in diagnosis, prevention, and management. Lancet Infect Dis 7(10):645–657PubMedGoogle Scholar
  10. 10.
    Wang A, Athan E, Pappas PA, Fowler VG Jr, Olaison L, Pare C, Almirante B, Munoz P, Rizzi M, Naber C, Logar M, Tattevin P, Iarussi DL, Selton-Suty C, Jones SB, Casabe J, Morris A, Corey GR, Cabell CH (2007) Contemporary clinical profile and outcome of prosthetic valve endocarditis. Jama 297(12):1354–1361PubMedGoogle Scholar
  11. 11.
    Cheung GY, Otto M (2010) Understanding the significance of Staphylococcus epidermidis bacteremia in babies and children. Curr Opin Infect Dis. doi: 10.1097/QCO.0b013e328337fecb
  12. 12.
    Anday EK, Talbot GH (1985) Coagulase-negative Staphylococcus bacteremia—a rising threat in the newborn infant. Ann Clin Lab Sci 15(3):246–251PubMedGoogle Scholar
  13. 13.
    Diekema DJ, Pfaller MA, Schmitz FJ, Smayevsky J, Bell J, Jones RN, Beach M (2001) Survey of infections due to Staphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, Latin America, Europe, and the Western Pacific region for the SENTRY Antimicrobial Surveillance Program, 1997–1999. Clin Infect Dis 32(Suppl 2):S114–S132PubMedGoogle Scholar
  14. 14.
    Chambers HF, Hartman BJ, Tomasz A (1985) Increased amounts of a novel penicillin-binding protein in a strain of methicillin-resistant Staphylococcus aureus exposed to nafcillin. J Clin Invest 76(1):325–331PubMedGoogle Scholar
  15. 15.
    Tomasz A, Nachman S, Leaf H (1991) Stable classes of phenotypic expression in methicillin-resistant clinical isolates of staphylococci. Antimicrob Agents Chemother 35(1):124–129PubMedGoogle Scholar
  16. 16.
    Jones RN (2006) Microbiological features of vancomycin in the 21st century: minimum inhibitory concentration creep, bactericidal/static activity, and applied breakpoints to predict clinical outcomes or detect resistant strains. Clin Infect Dis 42(Suppl 1):S13–S24PubMedGoogle Scholar
  17. 17.
    Costerton JW, Lewandowski Z, Caldwell DE, Korber DR, Lappin-Scott HM (1995) Microbial biofilms. Annu Rev Microbiol 49:711–745PubMedGoogle Scholar
  18. 18.
    Costerton JW, Stewart PS, Greenberg EP (1999) Bacterial biofilms: a common cause of persistent infections. Science 284(5418):1318–1322PubMedGoogle Scholar
  19. 19.
    Leid JG, Shirtliff ME, Costerton JW, Stoodley AP (2002) Human leukocytes adhere to, penetrate, and respond to Staphylococcus aureus biofilms. Infect Immun 70(11):6339–6345PubMedGoogle Scholar
  20. 20.
    Thurlow LR, Hanke ML, Fritz T, Angle A, Aldrich A, Williams SH, Engebretsen IL, Bayles KW, Horswill AR, Kielian T (2011) Staphylococcus aureus biofilms prevent macrophage phagocytosis and attenuate inflammation in vivo. J Immunol 186(11):6585–6596PubMedGoogle Scholar
  21. 21.
    Mah TF, O’Toole GA (2001) Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol 9(1):34–39PubMedGoogle Scholar
  22. 22.
    Walters MC 3rd, Roe F, Bugnicourt A, Franklin MJ, Stewart PS (2003) Contributions of antibiotic penetration, oxygen limitation, and low metabolic activity to tolerance of Pseudomonas aeruginosa biofilms to ciprofloxacin and tobramycin. Antimicrob Agents Chemother 47(1):317–323PubMedGoogle Scholar
  23. 23.
    Leite B, Gomes F, Teixeira P, Souza C, Pizzolitto E, Oliveira R (2011) In vitro activity of daptomycin, linezolid and rifampicin on Staphylococcus epidermidis biofilms. Curr Microbiol 63(3):313–317PubMedGoogle Scholar
  24. 24.
    Dunne WM Jr, Mason EO Jr, Kaplan SL (1993) Diffusion of rifampin and vancomycin through a Staphylococcus epidermidis biofilm. Antimicrob Agents Chemother 37(12):2522–2526PubMedGoogle Scholar
  25. 25.
    Keren I, Kaldalu N, Spoering A, Wang Y, Lewis K (2004) Persister cells and tolerance to antimicrobials. FEMS Microbiol Lett 230(1):13–18PubMedGoogle Scholar
  26. 26.
    Shapiro JA, Nguyen VL, Chamberlain NR (2011) Evidence for persisters in Staphylococcus epidermidis RP62a planktonic cultures and biofilms. J Med Microbiol 60(Pt 7):950–960PubMedGoogle Scholar
  27. 27.
    Yao Y, Sturdevant DE, Otto M (2005) Genomewide analysis of gene expression in Staphylococcus epidermidis biofilms: insights into the pathophysiology of S. epidermidis biofilms and the role of phenol-soluble modulins in formation of biofilms. J Infect Dis 191(2):289–298PubMedGoogle Scholar
  28. 28.
    Rodgers J, Phillips F, Olliff C (1994) The effects of extracellular slime from Staphylococcus epidermidis on phagocytic ingestion and killing. FEMS Immunol Med Microbiol 9(2):109–115PubMedGoogle Scholar
  29. 29.
    Johnson GM, Lee DA, Regelmann WE, Gray ED, Peters G, Quie PG (1986) Interference with granulocyte function by Staphylococcus epidermidis slime. Infect Immun 54(1):13–20PubMedGoogle Scholar
  30. 30.
    Noble MA, Reid PE, Park CM, Chan VY (1986) Inhibition of human neutrophil bacteriocidal activity by extracellular substance from slime-producing Staphylococcus epidermidis. Diagn Microbiol Infect Dis 4(4):335–339PubMedGoogle Scholar
  31. 31.
    Kristian SA, Birkenstock TA, Sauder U, Mack D, Gotz F, Landmann R (2008) Biofilm formation induces C3a release and protects Staphylococcus epidermidis from IgG and complement deposition and from neutrophil-dependent killing. J Infect Dis 197(7):1028–1035PubMedGoogle Scholar
  32. 32.
    Otto M (2006) Bacterial evasion of antimicrobial peptides by biofilm formation. Curr Top Microbiol Immunol 306:251–258PubMedGoogle Scholar
  33. 33.
    O’Toole G, Kaplan HB, Kolter R (2000) Biofilm formation as microbial development. Annu Rev Microbiol 54:49–79PubMedGoogle Scholar
  34. 34.
    Wang R, Khan BA, Cheung GY, Bach TH, Jameson-Lee M, Kong KF, Queck SY, Otto M (2011) Staphylococcus epidermidis surfactant peptides promote biofilm maturation and dissemination of biofilm-associated infection in mice. J Clin Invest 121(1):238–248PubMedGoogle Scholar
  35. 35.
    Boles BR, Thoendel M, Singh PK (2005) Rhamnolipids mediate detachment of Pseudomonas aeruginosa from biofilms. Mol Microbiol 57(5):1210–1223PubMedGoogle Scholar
  36. 36.
    Branda SS, Gonzalez-Pastor JE, Ben-Yehuda S, Losick R, Kolter R (2001) Fruiting body formation by Bacillus subtilis. Proc Natl Acad Sci U S A 98(20):11621–11626PubMedGoogle Scholar
  37. 37.
    Foster TJ, Hook M (1998) Surface protein adhesins of Staphylococcus aureus. Trends Microbiol 6(12):484–488PubMedGoogle Scholar
  38. 38.
    Bowden MG, Chen W, Singvall J, Xu Y, Peacock SJ, Valtulina V, Speziale P, Hook M (2005) Identification and preliminary characterization of cell-wall-anchored proteins of Staphylococcus epidermidis. Microbiology 151(Pt 5):1453–1464PubMedGoogle Scholar
  39. 39.
    Davis SL, Gurusiddappa S, McCrea KW, Perkins S, Hook M (2001) SdrG, a fibrinogen-binding bacterial adhesin of the microbial surface components recognizing adhesive matrix molecules subfamily from Staphylococcus epidermidis, targets the thrombin cleavage site in the Bbeta chain. J Biol Chem 276(30):27799–27805PubMedGoogle Scholar
  40. 40.
    Hartford O, O’Brien L, Schofield K, Wells J, Foster TJ (2001) The Fbe (SdrG) protein of Staphylococcus epidermidis HB promotes bacterial adherence to fibrinogen. Microbiology 147(Pt 9):2545–2552PubMedGoogle Scholar
  41. 41.
    Williams RJ, Henderson B, Sharp LJ, Nair SP (2002) Identification of a fibronectin-binding protein from Staphylococcus epidermidis. Infect Immun 70(12):6805–6810PubMedGoogle Scholar
  42. 42.
    Heilmann C, Hussain M, Peters G, Gotz F (1997) Evidence for autolysin-mediated primary attachment of Staphylococcus epidermidis to a polystyrene surface. Mol Microbiol 24(5):1013–1024PubMedGoogle Scholar
  43. 43.
    Heilmann C, Thumm G, Chhatwal GS, Hartleib J, Uekotter A, Peters G (2003) Identification and characterization of a novel autolysin (Aae) with adhesive properties from Staphylococcus epidermidis. Microbiology 149(Pt 10):2769–2778PubMedGoogle Scholar
  44. 44.
    Bowden MG, Visai L, Longshaw CM, Holland KT, Speziale P, Hook M (2002) Is the GehD lipase from Staphylococcus epidermidis a collagen binding adhesin? J Biol Chem 277(45):43017–43023PubMedGoogle Scholar
  45. 45.
    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(5428):760–763PubMedGoogle Scholar
  46. 46.
    Heilmann C (2011) Adhesion mechanisms of staphylococci. Adv Exp Med Biol 715:105–123PubMedGoogle Scholar
  47. 47.
    Mack D, Fischer W, Krokotsch A, Leopold K, Hartmann R, Egge H, Laufs R (1996) The intercellular adhesin involved in biofilm accumulation of Staphylococcus epidermidis is a linear beta-1,6-linked glucosaminoglycan: purification and structural analysis. J Bacteriol 178(1):175–183PubMedGoogle Scholar
  48. 48.
    Heilmann C, Schweitzer O, Gerke C, Vanittanakom N, Mack D, Gotz F (1996) Molecular basis of intercellular adhesion in the biofilm-forming Staphylococcus epidermidis. Mol Microbiol 20(5):1083–1091PubMedGoogle Scholar
  49. 49.
    Conlon KM, Humphreys H, O’Gara JP (2002) Regulation of icaR gene expression in Staphylococcus epidermidis. FEMS Microbiol Lett 216(2):171–177PubMedGoogle Scholar
  50. 50.
    Conlon KM, Humphreys H, O’Gara JP (2002) icaR encodes a transcriptional repressor involved in environmental regulation of ica operon expression and biofilm formation in Staphylococcus epidermidis. J Bacteriol 184(16):4400–4408PubMedGoogle Scholar
  51. 51.
    Jefferson KK, Pier DB, Goldmann DA, Pier GB (2004) The teicoplanin-associated locus regulator (TcaR) and the intercellular adhesin locus regulator (IcaR) are transcriptional inhibitors of the ica locus in Staphylococcus aureus. J Bacteriol 186(8):2449–2456PubMedGoogle Scholar
  52. 52.
    Handke LD, Slater SR, Conlon KM, O’Donnell ST, Olson ME, Bryant KA, Rupp ME, O’Gara JP, Fey PD (2007) SigmaB and SarA independently regulate polysaccharide intercellular adhesin production in Staphylococcus epidermidis. Can J Microbiol 53(1):82–91PubMedGoogle Scholar
  53. 53.
    Li M, Villaruz AE, Vadyvaloo V, Sturdevant DE, Otto M (2008) AI-2-dependent gene regulation in Staphylococcus epidermidis. BMC Microbiol 8:4PubMedGoogle Scholar
  54. 54.
    Vuong C, Gerke C, Somerville GA, Fischer ER, Otto M (2003) Quorum-sensing control of biofilm factors in Staphylococcus epidermidis. J Infect Dis 188(5):706–718PubMedGoogle Scholar
  55. 55.
    Gerke C, Kraft A, Sussmuth R, Schweitzer O, Gotz F (1998) Characterization of the N-acetylglucosaminyltransferase activity involved in the biosynthesis of the Staphylococcus epidermidis polysaccharide intercellular adhesin. J Biol Chem 273(29):18586–18593PubMedGoogle Scholar
  56. 56.
    Vuong C, Kocianova S, Voyich JM, Yao Y, Fischer ER, DeLeo FR, Otto M (2004) A crucial role for exopolysaccharide modification in bacterial biofilm formation, immune evasion, and virulence. J Biol Chem 279(52):54881–54886PubMedGoogle Scholar
  57. 57.
    Maira-Litran T, Kropec A, Goldmann DA, Pier GB (2005) Comparative opsonic and protective activities of Staphylococcus aureus conjugate vaccines containing native or deacetylated staphylococcal poly-N-acetyl-beta-(1–6)-glucosamine. Infect Immun 73(10):6752–6762PubMedGoogle Scholar
  58. 58.
    Mack D, Haeder M, Siemssen N, Laufs R (1996) Association of biofilm production of coagulase-negative staphylococci with expression of a specific polysaccharide intercellular adhesin. J Infect Dis 174(4):881–884PubMedGoogle Scholar
  59. 59.
    Kogan G, Sadovskaya I, Chaignon P, Chokr A, Jabbouri S (2006) Biofilms of clinical strains of Staphylococcus that do not contain polysaccharide intercellular adhesin. FEMS Microbiol Lett 255(1):11–16PubMedGoogle Scholar
  60. 60.
    Rohde H, Burandt EC, Siemssen N, Frommelt L, Burdelski C, Wurster S, Scherpe S, Davies AP, Harris LG, Horstkotte MA, Knobloch JK, Ragunath C, Kaplan JB, Mack D (2007) Polysaccharide intercellular adhesin or protein factors in biofilm accumulation of Staphylococcus epidermidis and Staphylococcus aureus isolated from prosthetic hip and knee joint infections. Biomaterials 28(9):1711–1720PubMedGoogle Scholar
  61. 61.
    Mack D, Riedewald J, Rohde H, Magnus T, Feucht HH, Elsner HA, Laufs R, Rupp ME (1999) Essential functional role of the polysaccharide intercellular adhesin of Staphylococcus epidermidis in hemagglutination. Infect Immun 67(2):1004–1008PubMedGoogle Scholar
  62. 62.
    Stevens NT, Sadovskaya I, Jabbouri S, Sattar T, O’Gara JP, Humphreys H, Greene CM (2009) Staphylococcus epidermidis polysaccharide intercellular adhesin induces IL-8 expression in human astrocytes via a mechanism involving TLR2. Cell Microbiol 11(3):421–432PubMedGoogle Scholar
  63. 63.
    Vuong C, Otto M (2008) The biofilm exopolysaccharide polysaccharide intercellular adhesin—a molecular and biochemical approach. Methods Mol Biol 431:97–106PubMedGoogle Scholar
  64. 64.
    Rupp ME, Fey PD, Heilmann C, Gotz F (2001) Characterization of the importance of Staphylococcus epidermidis autolysin and polysaccharide intercellular adhesin in the pathogenesis of intravascular catheter-associated infection in a rat model. J Infect Dis 183(7):1038–1042PubMedGoogle Scholar
  65. 65.
    Rupp ME, Ulphani JS, Fey PD, Bartscht K, Mack D (1999) Characterization of the importance of polysaccharide intercellular adhesin/hemagglutinin of Staphylococcus epidermidis in the pathogenesis of biomaterial-based infection in a mouse foreign body infection model. Infect Immun 67(5):2627–2632PubMedGoogle Scholar
  66. 66.
    Rupp ME, Ulphani JS, Fey PD, Mack D (1999) Characterization of Staphylococcus epidermidis polysaccharide intercellular adhesin/hemagglutinin in the pathogenesis of intravascular catheter-associated infection in a rat model. Infect Immun 67(5):2656–2659PubMedGoogle Scholar
  67. 67.
    Begun J, Gaiani JM, Rohde H, Mack D, Calderwood SB, Ausubel FM, Sifri CD (2007) Staphylococcal biofilm exopolysaccharide protects against Caenorhabditis elegans immune defenses. PLoS Pathog 3(4):e57PubMedGoogle Scholar
  68. 68.
    Kristian SA, Golda T, Ferracin F, Cramton SE, Neumeister B, Peschel A, Gotz F, Landmann R (2004) The ability of biofilm formation does not influence virulence of Staphylococcus aureus and host response in a mouse tissue cage infection model. Microb Pathog 36(5):237–245PubMedGoogle Scholar
  69. 69.
    Chokr A, Leterme D, Watier D, Jabbouri S (2007) Neither the presence of ica locus, nor in vitro-biofilm formation ability is a crucial parameter for some Staphylococcus epidermidis strains to maintain an infection in a guinea pig tissue cage model. Microb Pathog 42(2–3):94–97PubMedGoogle Scholar
  70. 70.
    Glaser L (1973) Bacterial cell surface polysaccharides. Annu Rev Biochem 42:91–112PubMedGoogle Scholar
  71. 71.
    Sadovskaya I, Vinogradov E, Li J, Jabbouri S (2004) Structural elucidation of the extracellular and cell-wall teichoic acids of Staphylococcus epidermidis RP62A, a reference biofilm-positive strain. Carbohydr Res 339(8):1467–1473PubMedGoogle Scholar
  72. 72.
    Lambert PA, Worthington T, Tebbs SE, Elliott TS (2000) Lipid S, a novel Staphylococcus epidermidis exocellular antigen with potential for the serodiagnosis of infections. FEMS Immunol Med Microbiol 29(3):195–202PubMedGoogle Scholar
  73. 73.
    Queck SY, Khan BA, Wang R, Bach TH, Kretschmer D, Chen L, Kreiswirth BN, Peschel A, DeLeo FR, Otto M (2009) Mobile genetic element-encoded cytolysin connects virulence to methicillin resistance in MRSA. PLoS Pathog 5(7):e1000533PubMedGoogle Scholar
  74. 74.
    Gross M, Cramton SE, Gotz F, Peschel A (2001) Key role of teichoic acid net charge in Staphylococcus aureus colonization of artificial surfaces. Infect Immun 69(5):3423–3426PubMedGoogle Scholar
  75. 75.
    Weidenmaier C, Kokai-Kun JF, Kristian SA, Chanturiya T, Kalbacher H, Gross M, Nicholson G, Neumeister B, Mond JJ, Peschel A (2004) Role of teichoic acids in Staphylococcus aureus nasal colonization, a major risk factor in nosocomial infections. Nat Med 10(3):243–245PubMedGoogle Scholar
  76. 76.
    Weidenmaier C, Peschel A (2008) Teichoic acids and related cell-wall glycopolymers in Gram-positive physiology and host interactions. Nat Rev Microbiol 6(4):276–287PubMedGoogle Scholar
  77. 77.
    Hussain M, Heilmann C, Peters G, Herrmann M (2001) Teichoic acid enhances adhesion of Staphylococcus epidermidis to immobilized fibronectin. Microb Pathog 31(6):261–270PubMedGoogle Scholar
  78. 78.
    Holland LM, Conlon B, O’Gara JP (2011) Mutation of tagO reveals an essential role for wall teichoic acids in Staphylococcus epidermidis biofilm development. Microbiology 157(Pt 2):408–418PubMedGoogle Scholar
  79. 79.
    Peschel A, Otto M, Jack RW, Kalbacher H, Jung G, Gotz F (1999) Inactivation of the dlt operon in Staphylococcus aureus confers sensitivity to defensins, protegrins, and other antimicrobial peptides. J Biol Chem 274(13):8405–8410PubMedGoogle Scholar
  80. 80.
    Li M, Cha DJ, Lai Y, Villaruz AE, Sturdevant DE, Otto M (2007) The antimicrobial peptide-sensing system aps of Staphylococcus aureus. Mol Microbiol 66(5):1136–1147PubMedGoogle Scholar
  81. 81.
    Peschel A, Jack RW, Otto M, Collins LV, Staubitz P, Nicholson G, Kalbacher H, Nieuwenhuizen WF, Jung G, Tarkowski A, van Kessel KP, van Strijp JA (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 l-lysine. J Exp Med 193(9):1067–1076PubMedGoogle Scholar
  82. 82.
    Li M, Lai Y, Villaruz AE, Cha DJ, Sturdevant DE, Otto M (2007) Gram-positive three-component antimicrobial peptide-sensing system. Proc Natl Acad Sci U S A 104(22):9469–9474PubMedGoogle Scholar
  83. 83.
    Hussain M, Herrmann M, von Eiff C, Perdreau-Remington F, Peters G (1997) A 140-kilodalton extracellular protein is essential for the accumulation of Staphylococcus epidermidis strains on surfaces. Infect Immun 65(2):519–524PubMedGoogle Scholar
  84. 84.
    Banner MA, Cunniffe JG, Macintosh RL, Foster TJ, Rohde H, Mack D, Hoyes E, Derrick J, Upton M, Handley PS (2007) Localized tufts of fibrils on Staphylococcus epidermidis NCTC 11047 are comprised of the accumulation-associated protein. J Bacteriol 189(7):2793–2804PubMedGoogle Scholar
  85. 85.
    Conrady DG, Brescia CC, Horii K, Weiss AA, Hassett DJ, Herr AB (2008) A zinc-dependent adhesion module is responsible for intercellular adhesion in staphylococcal biofilms. Proc Natl Acad Sci U S A 105(49):19456–19461PubMedGoogle Scholar
  86. 86.
    Rohde H, Burdelski C, Bartscht K, Hussain M, Buck F, Horstkotte MA, Knobloch JK, Heilmann C, Herrmann M, Mack D (2005) Induction of Staphylococcus epidermidis biofilm formation via proteolytic processing of the accumulation-associated protein by staphylococcal and host proteases. Mol Microbiol 55(6):1883–1895PubMedGoogle Scholar
  87. 87.
    Macintosh RL, Brittan JL, Bhattacharya R, Jenkinson HF, Derrick J, Upton M, Handley PS (2009) The terminal A domain of the fibrillar accumulation-associated protein (Aap) of Staphylococcus epidermidis mediates adhesion to human corneocytes. J Bacteriol 191(22):7007–7016PubMedGoogle Scholar
  88. 88.
    Christner M, Franke GC, Schommer NN, Wendt U, Wegert K, Pehle P, Kroll G, Schulze C, Buck F, Mack D, Aepfelbacher M, Rohde H (2010) The giant extracellular matrix-binding protein of Staphylococcus epidermidis mediates biofilm accumulation and attachment to fibronectin. Mol Microbiol 75(1):187–207PubMedGoogle Scholar
  89. 89.
    Cucarella C, Solano C, Valle J, Amorena B, Lasa I, Penades JR (2001) Bap, a Staphylococcus aureus surface protein involved in biofilm formation. J Bacteriol 183(9):2888–2896PubMedGoogle Scholar
  90. 90.
    Tormo MA, Knecht E, Gotz F, Lasa I, Penades JR (2005) Bap-dependent biofilm formation by pathogenic species of Staphylococcus: evidence of horizontal gene transfer? Microbiology 151(Pt 7):2465–2475PubMedGoogle Scholar
  91. 91.
    Lasa I, Penades JR (2006) Bap: a family of surface proteins involved in biofilm formation. Res Microbiol 157(2):99–107PubMedGoogle Scholar
  92. 92.
    Davies DG, Parsek MR, Pearson JP, Iglewski BH, Costerton JW, Greenberg EP (1998) The involvement of cell-to-cell signals in the development of a bacterial biofilm. Science 280(5361):295–298PubMedGoogle Scholar
  93. 93.
    Yarwood JM, Bartels DJ, Volper EM, Greenberg EP (2004) Quorum sensing in Staphylococcus aureus biofilms. J Bacteriol 186(6):1838–1850PubMedGoogle Scholar
  94. 94.
    Vuong C, Saenz HL, Gotz F, Otto M (2000) Impact of the agr quorum-sensing system on adherence to polystyrene in Staphylococcus aureus. J Infect Dis 182(6):1688–1693PubMedGoogle Scholar
  95. 95.
    Vuong C, Kocianova S, Yao Y, Carmody AB, Otto M (2004) Increased colonization of indwelling medical devices by quorum-sensing mutants of Staphylococcus epidermidis in vivo. J Infect Dis 190(8):1498–1505PubMedGoogle Scholar
  96. 96.
    Boles BR, Horswill AR (2008) Agr-mediated dispersal of Staphylococcus aureus biofilms. PLoS Pathog 4(4):e1000052PubMedGoogle Scholar
  97. 97.
    Ashiuchi M, Misono H (2002) Biochemistry and molecular genetics of poly-gamma-glutamate synthesis. Appl Microbiol Biotechnol 59(1):9–14PubMedGoogle Scholar
  98. 98.
    Oppermann-Sanio FB, Steinbuchel A (2002) Occurrence, functions and biosynthesis of polyamides in microorganisms and biotechnological production. Naturwissenschaften 89(1):11–22PubMedGoogle Scholar
  99. 99.
    Kocianova S, Vuong C, Yao Y, Voyich JM, Fischer ER, DeLeo FR, Otto M (2005) Key role of poly-gamma-DL-glutamic acid in immune evasion and virulence of Staphylococcus epidermidis. J Clin Invest 115(3):688–694PubMedGoogle Scholar
  100. 100.
    Makino S, Uchida I, Terakado N, Sasakawa C, Yoshikawa M (1989) Molecular characterization and protein analysis of the cap region, which is essential for encapsulation in Bacillus anthracis. J Bacteriol 171(2):722–730PubMedGoogle Scholar
  101. 101.
    Foster TJ (2005) Immune evasion by staphylococci. Nat Rev Microbiol 3(12):948–958PubMedGoogle Scholar
  102. 102.
    Bautista L, Gaya P, Medina M, Nunez M (1988) A quantitative study of enterotoxin production by sheep milk staphylococci. Appl Environ Microbiol 54(2):566–569PubMedGoogle Scholar
  103. 103.
    Marin ME, de la Rosa MC, Cornejo I (1992) Enterotoxigenicity of Staphylococcus strains isolated from Spanish dry-cured hams. Appl Environ Microbiol 58(3):1067–1069PubMedGoogle Scholar
  104. 104.
    Madhusoodanan J, Seo KS, Remortel B, Park JY, Hwang SY, Fox LK, Park YH, Deobald CF, Wang D, Liu S, Daugherty SC, Gill AL, Bohach GA, Gill SR (2011) An enterotoxin-bearing pathogenicity island in Staphylococcus epidermidis. J Bacteriol 193(8):1854–1862PubMedGoogle Scholar
  105. 105.
    Marraffini LA, Sontheimer EJ (2008) CRISPR interference limits horizontal gene transfer in staphylococci by targeting DNA. Science 322(5909):1843–1845PubMedGoogle Scholar
  106. 106.
    Mehlin C, Headley CM, Klebanoff SJ (1999) An inflammatory polypeptide complex from Staphylococcus epidermidis: isolation and characterization. J Exp Med 189(6):907–918PubMedGoogle Scholar
  107. 107.
    Liles WC, Thomsen AR, O’Mahony DS, Klebanoff SJ (2001) Stimulation of human neutrophils and monocytes by staphylococcal phenol-soluble modulin. J Leukoc Biol 70(1):96–102PubMedGoogle Scholar
  108. 108.
    Hajjar AM, O’Mahony DS, Ozinsky A, Underhill DM, Aderem A, Klebanoff SJ, Wilson CB (2001) Cutting edge: functional interactions between toll-like receptor (TLR) 2 and TLR1 or TLR6 in response to phenol-soluble modulin. J Immunol 166(1):15–19PubMedGoogle Scholar
  109. 109.
    Kretschmer D, Gleske AK, Rautenberg M, Wang R, Koberle M, Bohn E, Schoneberg T, Rabiet MJ, Boulay F, Klebanoff SJ, van Kessel KA, van Strijp JA, Otto M, Peschel A (2010) Human formyl peptide receptor 2 senses highly pathogenic Staphylococcus aureus. Cell Host Microbe 7(6):463–473PubMedGoogle Scholar
  110. 110.
    Cheung GY, Rigby K, Wang R, Queck SY, Braughton KR, Whitney AR, Teintze M, DeLeo FR, Otto M (2010) Staphylococcus epidermidis strategies to avoid killing by human neutrophils. PLoS Pathog 6(10). doi: 10.1371/journal.ppat.1001133
  111. 111.
    Rautenberg M, Joo HS, Otto M, Peschel A (2011) Neutrophil responses to staphylococcal pathogens and commensals via the formyl peptide receptor 2 relates to phenol-soluble modulin release and virulence. FASEB J 25(4):1254–1263PubMedGoogle Scholar
  112. 112.
    Wang R, Braughton KR, Kretschmer D, Bach TH, Queck SY, Li M, Kennedy AD, Dorward DW, Klebanoff SJ, Peschel A, DeLeo FR, Otto M (2007) Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA. Nat Med 13(12):1510–1514PubMedGoogle Scholar
  113. 113.
    Vuong C, Durr M, Carmody AB, Peschel A, Klebanoff SJ, Otto M (2004) Regulated expression of pathogen-associated molecular pattern molecules in Staphylococcus epidermidis: quorum-sensing determines pro-inflammatory capacity and production of phenol-soluble modulins. Cell Microbiol 6(8):753–759PubMedGoogle Scholar
  114. 114.
    McKevitt AI, Bjornson GL, Mauracher CA, Scheifele DW (1990) Amino acid sequence of a deltalike toxin from Staphylococcus epidermidis. Infect Immun 58(5):1473–1475PubMedGoogle Scholar
  115. 115.
    Gill SR, Fouts DE, Archer GL, Mongodin EF, Deboy RT, Ravel J, Paulsen IT, Kolonay JF, Brinkac L, Beanan M, Dodson RJ, Daugherty SC, Madupu R, Angiuoli SV, Durkin AS, Haft DH, Vamathevan J, Khouri H, Utterback T, Lee C, Dimitrov G, Jiang L, Qin H, Weidman J, Tran K, Kang K, Hance IR, Nelson KE, Fraser CM (2005) Insights on evolution of virulence and resistance from the complete genome analysis of an early methicillin-resistant Staphylococcus aureus strain and a biofilm-producing methicillin-resistant Staphylococcus epidermidis strain. J Bacteriol 187(7):2426–2438PubMedGoogle Scholar
  116. 116.
    Zhang YQ, Ren SX, Li HL, Wang YX, Fu G, Yang J, Qin ZQ, Miao YG, Wang WY, Chen RS, Shen Y, Chen Z, Yuan ZH, Zhao GP, Qu D, Danchin A, Wen YM (2003) Genome-based analysis of virulence genes in a non-biofilm-forming Staphylococcus epidermidis strain (ATCC 12228). Mol Microbiol 49(6):1577–1593PubMedGoogle Scholar
  117. 117.
    Lai Y, Villaruz AE, Li M, Cha DJ, Sturdevant DE, Otto M (2007) The human anionic antimicrobial peptide dermcidin induces proteolytic defence mechanisms in staphylococci. Mol Microbiol 63(2):497–506PubMedGoogle Scholar
  118. 118.
    Dubin G, Chmiel D, Mak P, Rakwalska M, Rzychon M, Dubin A (2001) Molecular cloning and biochemical characterisation of proteases from Staphylococcus epidermidis. Biol Chem 382(11):1575–1582PubMedGoogle Scholar
  119. 119.
    Iwase T, Uehara Y, Shinji H, Tajima A, Seo H, Takada K, Agata T, Mizunoe Y (2010) Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization. Nature 465(7296):346–349PubMedGoogle Scholar
  120. 120.
    Farrell AM, Foster TJ, Holland KT (1993) Molecular analysis and expression of the lipase of Staphylococcus epidermidis. J Gen Microbiol 139(2):267–277PubMedGoogle Scholar
  121. 121.
    Simons JW, van Kampen MD, Riel S, Gotz F, Egmond MR, Verheij HM (1998) Cloning, purification and characterisation of the lipase from Staphylococcus epidermidis—comparison of the substrate selectivity with those of other microbial lipases. Eur J Biochem 253(3):675–683PubMedGoogle Scholar
  122. 122.
    Chamberlain NR, Brueggemann SA (1997) Characterisation and expression of fatty acid modifying enzyme produced by Staphylococcus epidermidis. J Med Microbiol 46(8):693–697PubMedGoogle Scholar
  123. 123.
    von Eiff C, Becker K, Machka K, Stammer H, Peters G (2001) Nasal carriage as a source of Staphylococcus aureus bacteremia. Study Group. N Engl J Med 344(1):11–16Google Scholar
  124. 124.
    Ji G, Beavis R, Novick RP (1997) Bacterial interference caused by autoinducing peptide variants. Science 276(5321):2027–2030PubMedGoogle Scholar
  125. 125.
    Otto M, Echner H, Voelter W, Gotz F (2001) Pheromone cross-inhibition between Staphylococcus aureus and Staphylococcus epidermidis. Infect Immun 69(3):1957–1960PubMedGoogle Scholar
  126. 126.
    Lina G, Boutite F, Tristan A, Bes M, Etienne J, Vandenesch F (2003) Bacterial competition for human nasal cavity colonization: role of staphylococcal agr alleles. Appl Environ Microbiol 69(1):18–23PubMedGoogle Scholar
  127. 127.
    Krismer B, Peschel A (2011) Does Staphylococcus aureus nasal colonization involve biofilm formation? Future Microbiol 6(5):489–493. doi: 10.2217/fmb.11.37 PubMedGoogle Scholar
  128. 128.
    Massey RC, Horsburgh MJ, Lina G, Hook M, Recker M (2006) The evolution and maintenance of virulence in Staphylococcus aureus: a role for host-to-host transmission? Nat Rev Microbiol 4(12):953–958PubMedGoogle Scholar
  129. 129.
    Yao Y, Sturdevant DE, Villaruz A, Xu L, Gao Q, Otto M (2005) Factors characterizing Staphylococcus epidermidis invasiveness determined by comparative genomics. Infect Immun 73(3):1856–1860PubMedGoogle Scholar
  130. 130.
    Kozitskaya S, Cho SH, Dietrich K, Marre R, Naber K, Ziebuhr W (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(2):1210–1215PubMedGoogle Scholar
  131. 131.
    Gu J, Li H, Li M, Vuong C, Otto M, Wen Y, Gao Q (2005) Bacterial insertion sequence IS256 as a potential molecular marker to discriminate invasive strains from commensal strains of Staphylococcus epidermidis. J Hosp Infect 61(4):342–348PubMedGoogle Scholar
  132. 132.
    Li M, Wang X, Gao Q, Lu Y (2009) Molecular characterization of Staphylococcus epidermidis strains isolated from a teaching hospital in Shanghai, China. J Med Microbiol 58(Pt 4):456–461PubMedGoogle Scholar
  133. 133.
    Galdbart JO, Allignet J, Tung HS, Ryden C, El Solh N (2000) Screening for Staphylococcus epidermidis markers discriminating between skin-flora strains and those responsible for infections of joint prostheses. J Infect Dis 182(1):351–355PubMedGoogle Scholar
  134. 134.
    Ziebuhr W, Krimmer V, Rachid S, Lossner I, Gotz F, Hacker J (1999) A novel mechanism of phase variation of virulence in Staphylococcus epidermidis: evidence for control of the polysaccharide intercellular adhesin synthesis by alternating insertion and excision of the insertion sequence element IS256. Mol Microbiol 32(2):345–356PubMedGoogle Scholar
  135. 135.
    Rogers KL, Rupp ME, Fey PD (2008) The presence of icaADBC is detrimental to the colonization of human skin by Staphylococcus epidermidis. Appl Environ Microbiol 74(19):6155–6157PubMedGoogle Scholar
  136. 136.
    Miragaia M, Thomas JC, Couto I, Enright MC, de Lencastre H (2007) Inferring a population structure for Staphylococcus epidermidis from multilocus sequence typing data. J Bacteriol 189(6):2540–2552PubMedGoogle Scholar
  137. 137.
    Rohde H, Kalitzky M, Kroger N, Scherpe S, Horstkotte MA, Knobloch JK, Zander AR, Mack D (2004) Detection of virulence-associated genes not useful for discriminating between invasive and commensal Staphylococcus epidermidis strains from a bone marrow transplant unit. J Clin Microbiol 42(12):5614–5619PubMedGoogle Scholar
  138. 138.
    Otto M (2009) Staphylococcus epidermidis—the ‘accidental’ pathogen. Nat Rev Microbiol 7:555–567PubMedGoogle Scholar

Copyright information

© US Government 2011

Authors and Affiliations

  1. 1.Pathogen Molecular Genetics SectionLaboratory of Human Bacterial Pathogenesis, NIAID, NIHBethesdaUSA

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