Infections of Orthopaedic Implants and Devices

Part of the Springer Series on Biofilms book series (BIOFILMS, volume 3)


Prosthetic implantation is rising in popularity in the United States, and use of prostheses will only continue to increase with the aging of the Baby Boomer generation. A concurrent rise in the number of infections of these implants is also being seen. Prosthetic implant infection (PII) can be caused by direct inoculation of bacteria to the implant or by seeding from the blood (hematogenous). Because the implant is quickly coated by host connective tissue upon implantation, bacteria such as the staphylococcal species S. aureus and S. epidermidis are able to readily gain a foothold in the host. S. aureus is able to quickly develop antibiotic resistance and methicillin-resistant strains (MRSA) are considered endemic in hospitals. This bacterium features a myriad of virulence factors that allow it to colonize and damage the host, as well as avoid the host immune response. These virulence factors are largely regulated through population-based quorum sensing via the agr system. S. aureus is also able to form biofilms, microbial communities encased in a polysaccharide matrix, which allows the bacteria within to persist in the face of antimicrobial therapies and the host response. Diagnosis of PII is difficult with many false results and confusion with aseptic loosening of the implant. Because of ineffective means of diagnosis, combined with S. aureus’ high incidence of antibiotic resistance and its ability to evade both antibiotics and the host response through biofilm formation, treatment for PII is often inadequate and infection can become chronic. Therefore, PII has a high rate of morbidity and mortality for patients, as well as an extreme economic burden on the US healthcare system.


Staphylococcus Aureus Orthopaedic Implant Infected Total Knee Arthroplasty Small Colony Variant Polysaccharide Intercellular Adhesin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Acharya KR, Passalacqua EF, Jones EY, Harlos K, Stuart DI, Brehm RD, Tranter HS (1994) Structural basis of superantigen action inferred from crystal structure of toxic-shock syndrome toxin-1. Nature 367:94–97PubMedGoogle Scholar
  2. Akiyama H, Torigoe R, Arata J (1993) Interaction of Staphylococcus aureus cells and silk threads in vitro and in mouse skin. J Dermatol Sci 6:247–257PubMedGoogle Scholar
  3. Akiyama H, Ueda M, Kanzaki H, Tada J, Arata J (1997) Biofilm formation of Staphylococcus aureus strains isolated from impetigo and furuncle: role of fibrinogen and fibrin. J Environ Pathol Toxicol 16:2–10Google Scholar
  4. Alexander EH and Hudson MC (2001) Factors influencing the internalization of Staphylococcus aureus and impacts on the course of infections in humans. Appl Microbiol Biotechnol 56:361–366PubMedGoogle Scholar
  5. Andersson JA, Cervin A, Lindberg S, Uddman R, Cardeil LO (2002) The paranasal sinuses as reservoirs for nitric oxide. Acta Otolaryngol 122:861–865PubMedGoogle Scholar
  6. Arciola CR, Gamberini S, Campoccia D, Visai L, Speziale P, Baldassarri L, Montanaro L (2005) A multiplex PCR method for the detection of all five individual genes of ica locus in Staphylococcus epidermidis. A survey on 400 clinical isolates from prosthesis-associated infections. J Biomed Mater Res A 75:408–413PubMedGoogle Scholar
  7. Arrizubieta MJ, Toledo-Arana A, Amorena B, Penades JR, Lasa I (2004) Calcium inhibits bap-dependent multicellular behavior in Staphylococcus aureus. J Bacteriol 186:7490–7498PubMedGoogle Scholar
  8. Baker MD and Acharya KR (2004) Superantigens: structure-function relationships. Int J Med Microbiol 293:529–537PubMedGoogle Scholar
  9. Balaban N and Novick RP (1995) Autocrine regulation of toxin synthesis by Staphylococcus aureus. Proc Natl Acad Sci USA 92:1619–1623PubMedGoogle Scholar
  10. Balaban N, Goldkorn T, Nhan RT, Dang LB, Scott S, Ridgley RM, Rasooly A, Wright SC, Larrick JW, Rasooly R, Carlson JR (1998) Autoinducer of virulence as a target for vaccine and therapy against Staphylococcus aureus. Science 280:438–440PubMedGoogle Scholar
  11. Balaban N, Gov Y, Bitler A, Boelaert JR (2003) Prevention of Staphylococcus aureus biofilm on dialysis catheters and adherence to human cells. Kidney Int 63:340–345PubMedGoogle Scholar
  12. Balaban N, Stoodley P, Fux CA, Wilson S, Costerton JW, Dell’Acqua G (2005) Prevention of staphylococcal biofilm-associated infections by the quorum sensing inhibitor RIP. Clin Orthop Relat Res 48–54Google Scholar
  13. Batzilla CF, Rachid S, Engelmann S, Hecker M, Hacker J, Ziebuhr W (2006) Impact of the accessory gene regulatory system (Agr) on extracellular proteins, cod Y expression and amino acid metabolism in Staphylococcus epidermidis. Proteomics 6:3602–3613PubMedGoogle Scholar
  14. Bavari S and Ulrich RG (1995) Staphylococcal enterotoxin A and toxic shock syndrome toxin compete with CD4 for human major histocompatibility complex class II binding. Infect Immun 63:423–429PubMedGoogle Scholar
  15. Bayer MG, Heinrichs JH, Cheung AL (1996) The molecular architecture of the sar locus in Staphylococcus aureus. J Bacteriol 178:4563–4570PubMedGoogle Scholar
  16. Bayles KW, Wesson CA, Liou LE, Fox LK, Bohach GA, Trumble WR (1998) Intracellular Staphylococcus aureus escapes the endosome and induces apoptosis in epithelial cells. Infect Immun 66:336–342PubMedGoogle Scholar
  17. Becker P, Hufnagle W, Peters G, Herrmann M (2001) Detection of differential gene expression in biofilm-forming versus planktonic populations of Staphylococcus aureus using micro-representational-difference analysis. Appl Environ Microbiol 67:2958–2965PubMedGoogle Scholar
  18. Beenken KE, Blevins JS, Smeltzer MS (2003) Mutation of sarA in Staphylococcus aureus limits biofilm formation. Infect Immun 71:4206–4211PubMedGoogle Scholar
  19. Beenken KE, Dunman PM, McAleese F, Macapagal D, Murphy E, Projan SJ, Blevins JS, Smeltzer MS (2004) Global gene expression in Staphylococcus aureus biofilms. J Bacteriol 186:4665–4684PubMedGoogle Scholar
  20. Belmonte G, Cescatti L, Ferrari B, Nicolussi T, Ropele M, Menestrina G (1987) Pore formation by Staphylococcus aureus alpha-toxin in lipid bilayers. Dependence upon temperature and toxin concentration. Eur Biophys J 14:349–358PubMedGoogle Scholar
  21. Bernard L, Lubbeke A, Stern R, Bru JP, Feron JM, Peyramond D, Denormandie P, Arvieux C, Chirouze C, Perronne C, Hoffmeyer P (2004) Value of preoperative investigations in diagnosing prosthetic joint infection: retrospective cohort study and literature review. Scand J Infect Dis 36:410–416PubMedGoogle Scholar
  22. Beveridge TJ, Makin SA, Kadurugamuwa JL, Li Z (1997) Interactions between biofilms and the environment. FEMS Microbiol Rev 20:291–303PubMedGoogle Scholar
  23. Bhakdi S and Tranum-Jensen J (1991) Alpha-toxin of Staphylococcus aureus. Microbiol Rev 55:733–751PubMedGoogle Scholar
  24. Bhasin N, Albus A, Michon F, Livolsi PJ, Park JS, Lee JC (1998) Identification of a gene essential for O-acetylation of the Staphylococcus aureus type 5 capsular polysaccharide. Mol Microbiol 27:9–21PubMedGoogle Scholar
  25. Birch JG and Samchukov ML (2004) Use of the Ilizarov method to correct lower limb deformities in children and adolescents. J Am Acad Orthop Surg 12:144–154PubMedGoogle Scholar
  26. Boelens JJ, van der Poll T, Dankert J, Zaat SA (2000) Interferon-gamma protects against biomaterial-associated Staphylococcus epidermidis infection in mice. J Infect Dis 181:1167–1171PubMedGoogle Scholar
  27. Boles BR and Horswill AR (2008) Agr-mediated dispersal of Staphylococcus aureus biofilms. PLoS Pathog 4:e 1000052Google Scholar
  28. Bost KL, Ramp WK, Nicholson NC, Bento JL, Marriott I, Hudson MC (1999) Staphylococcus aureus infection of mouse or human osteoblasts induces high levels of interleukin-6 and interleukin-12 production. J Infect Dis 180:1912–1920PubMedGoogle Scholar
  29. Boyd A and Chakrabarty AM (1994) Role of alginate lyase in cell detachment of Pseudomonas aeruginosa. Appl Environ Microbiol 60:2355–2359PubMedGoogle Scholar
  30. Brady RA, Leid JG, Kofonow J, Costerton JW, Shirtliff ME (2007) Immunoglobulins to surface-associated biofilm immunogens provide a novel means of visualization of methicillin-resistant Staphylococcus aureus biofilms. Appl Environ Microbiol 73:6612–6619PubMedGoogle Scholar
  31. Brown MR, Allison DG, Gilbert P (1988) Resistance of bacterial biofilms to antibiotics: a growth-rate related effect? J Antimicrob Chemother 22:777–780PubMedGoogle Scholar
  32. Bureau NJ, Chhem RK, Cardinal E (1999) Musculoskeletal infections: US manifestations. Radiographics 19:1585–1592PubMedGoogle Scholar
  33. Butt WP (1973) The radiology of infection. Clin Orthop 96:20–30PubMedGoogle Scholar
  34. Cafiso V, Bertuccio T, Santagati M, Campanile F, Amicosante G, Perilli MG, Selan L, Artini M, Nicoletti G, Stefani S (2004) Presence of the ica operon in clinical isolates of Staphylococcus epidermidis and its role in biofilm production. Clin Microbiol Infect 10:1081–1088PubMedGoogle Scholar
  35. Cafiso V, Bertuccio T, Santagati M, Demelio V, Spina D, Nicoletti G, Stefani S (2007) agr-Genotyping and transcriptional analysis of biofilm-producing Staphylococcus aureus. FEMS Immunol Med Microbiol 51:220–227PubMedGoogle Scholar
  36. Caiazza NC and O’Toole GA (2003) Alpha-toxin is required for biofilm formation by Staphylococcus aureus. J Bacteriol 185:3214–3217PubMedGoogle Scholar
  37. Camargo IL and Gilmore MS (2008) Staphylococcus aureus—probing for host weakness? J Bacteriol 190:2253–2256PubMedGoogle Scholar
  38. Carek PJ, Dickerson LM, Sack JL (2001) Diagnosis and management of osteomyelitis. Am Fam Physician 63:2413–2420PubMedGoogle Scholar
  39. Centers for Disease Control (2003) Methicillin-resistant Staphylococcus aureus infections among competitive sports participants — Colorado, Indiana, Pennsylvania, and Los Angeles County, 2000–2003. Conn Med 67:549–551Google Scholar
  40. Cerca N, Martins S, Cerca F, Jefferson KK, Pier GB, Oliveira R, Azeredo J (2005) Comparative assessment of antibiotic susceptibility of coagulase-negative staphylococci in biofilm versus planktonic culture as assessed by bacterial enumeration or rapid XTT colorimetry. J Antimicrob Chemother 56:331–336PubMedGoogle Scholar
  41. Chakrabarti SK and Misra TK (2000) SarA represses agr operon expression in a purified in vitro Staphylococcus aureus transcription system. J Bacteriol 182:5893–5897PubMedGoogle Scholar
  42. Chan C, Burrows LL, Deber CM (2004) Helix induction in antimicrobial peptides by alginate in biofilms. J Biol Chem 279:38749–38754PubMedGoogle Scholar
  43. Chan PF and Foster SJ (1998) Role of SarA in virulence determinant production and environmental signal transduction in Staphylococcus aureus. J Bacteriol 180:6232–6241PubMedGoogle Scholar
  44. Chan WC, Coyle BJ, Williams P (2004) Virulence regulation and quorum sensing in staphylococcal infections: competitive AgrC antagonists as quorum sensing inhibitors. J Med Chem 47:4633–4641PubMedGoogle Scholar
  45. Chatterjee I, Becker P, Grundmeier M, Bischoff M, Somerville GA, Peters G, Sinha B, Harraghy N, Proctor RA, Herrmann M (2005) Staphylococcus aureus ClpC is required for stress resistance, aconitase activity, growth recovery, and death. J Bacteriol 187:4488–4496PubMedGoogle Scholar
  46. Chen C, Brown DR, Xie Y, Green BT, Lyte M (2003) Catecholamines modulate Escherichia coli O157:H7 adherence to murine cecal mucosa. Shock 20:183–188PubMedGoogle Scholar
  47. Chuard C, Vaudaux PE, Proctor RA, Lew DP (1997) Decreased susceptibility to antibiotic killing of a stable small colony variant of Staphylococcus aureus in fluid phase and on fibronectincoated surfaces. J Antimicrob Chemother 39:603–608PubMedGoogle Scholar
  48. Clasper JC and Phillips SL (2005) Early failure of external fixation in the management of war injuries. J R Army Med Corps 151:81–86PubMedGoogle Scholar
  49. 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 184:4400–4408PubMedGoogle Scholar
  50. Corrigan RM, Rigby D, Handley P, Foster TJ (2007) The role of Staphylococcus aureus surface protein SasG in adherence and biofilm formation. Microbiology 153:2435–2446PubMedGoogle Scholar
  51. Costerton JW, Lewandowski Z, Caldwell DE, Korber DR, Lappin-Scott HM (1995) Microbial biofilms. Annu Rev Microbiol 49:711–745PubMedGoogle Scholar
  52. Cramton SE, Gerke C, Schnell NF, Nichols WW, Gotz F (1999) The intercellular adhesion (ica) locus is present in Staphylococcus aureus and is required for biofilm formation. Infect Immun 67:5427–5433PubMedGoogle Scholar
  53. Cramton SE, Ulrich M, Gotz F, Doring G (2001) Anaerobic conditions induce expression of polysaccharide intercellular adhesin in Staphylococcus aureus and Staphylococcus epidermidis. Infect Immun 69:4079–4085PubMedGoogle Scholar
  54. Cuckler JM, Star AM, Alavi A, Noto RB (1991) Diagnosis and management of the infected total joint arthroplasty. Orthop Clin North Am 22:523–530PubMedGoogle Scholar
  55. Cunnion KM, Lee JC, Frank MM (2001) Capsule production and growth phase influence binding of complement to Staphylococcus aureus. Infect Immun 69:6796–6803PubMedGoogle Scholar
  56. Dagher F and Roukoz S (1991) Compound tibial fractures with bone loss treated by the Ilizarov technique. J Bone Joint Surg Br Vol 73:316–321Google Scholar
  57. Dahl A and Toksvig-Larsen S (2004) Pin site care in external fixation sodium chloride or chlorhexidine solution as a cleansing agent. Arch Orthop Trauma Surg 124:555–558Google Scholar
  58. Datz FL, Jacobs J, Baker W, Landrum W, Alazraki N, Taylor AJ (1984) Decreased sensitivity of early imaging with In-111 oxine-labeled leukocytes in detection of occult infection: concise communication. J Nucl Med 25:303–306PubMedGoogle Scholar
  59. Davies R, Holt N, Nayagam S (2005) The care of pin sites with external fixation. J Bone Joint Surg Br 87:716–719PubMedGoogle Scholar
  60. De Beer D, Srinivasan R, Stewart PS (1994) Direct measurement of chlorine penetration into biofilms during disinfection. Appl Environ Microbiol 60:4339–4344PubMedGoogle Scholar
  61. Dell’Acqua G, Giacometti A, Cirioni O, Ghiselli R, Saba V, Scalise G, Gov Y, Balaban N (2004) Suppression of drug-resistant Staphylococcal Infections by the quorum-sensing inhibitor RNAIII-inhibiting peptide. J Infect Dis 190:318–320PubMedGoogle Scholar
  62. Dinges MM, Orwin PM, Schlievert PM (2000) Exotoxins of Staphylococcus aureus. Clin Microbiol Rev 13:16–34PubMedGoogle Scholar
  63. Doery HM, Magnusson BJ, Cheyne IM, Sulasekharam J (1963) A phospholipase in staphylococcal toxin which hydrolyses sphingomyelin. Nature 198:1091–1092PubMedGoogle Scholar
  64. Donlan RM and Costerton JW (2002) Biofilms: survival mechanisms of clinically relevant micro-organisms. Clin Microbiol Rev 15:167–193PubMedGoogle Scholar
  65. Dubrac S, Boneca IG, Msadek T (2007) New insights into the WalK/WalR (YycG/YycF) essential signal transduction pathway reveal a major role in controlling cell wall metabolism and biofilm formation in Staphylococcus aureus. J Bacteriol 189:8257–8269PubMedGoogle Scholar
  66. Duff GP, Lachiewicz PF, Kelley SS (1996) Aspiration of the knee joint before revision arthroplasty. Clin Orthop Relat Res 132–139Google Scholar
  67. Dunman PM, Murphy E, Haney S, Palacios D, Tucker-Kellogg G, Wu S, Brown EL, Zagursky RJ, Shlaes D, Projan SJ (2001) Transcription profiling-based identification of Staphylococcus aureus genes regulated by the agr and/or sarA loci. J Bacteriol 183:7341–7353PubMedGoogle Scholar
  68. Dziewanowska K, Patti JM, Deobald CF, Bayles KW, Trumble WR, Bohach GA (1999) Fibronectin binding protein and host cell tyrosine kinase are required for internalization of Staphylococcus aureus by epithelial cells. Infect Immun 67:4673–4678PubMedGoogle Scholar
  69. Everts RJ, Chambers ST, Murdoch DR, Rothwell AG, McKie J (2004) Successful antimicrobial therapy and implant retention for streptococcal infection of prosthetic joints. ANZ J Surg 74:210–214PubMedGoogle Scholar
  70. Fallgren C, Utt M, Ljungh A (2001) Isolation and characterisation of a 17-kDa staphylococcal heparin-binding protein with broad specificity. J Med Microbiol 50:547–557PubMedGoogle Scholar
  71. Fedtke I, Mader D, Kohler T, Moll H, Nicholson G, Biswas R, Henseler K, Gotz F, Zahringer U, Peschel A (2007) A Staphylococcus aureus ypfP mutant with strongly reduced lipoteichoic acid (LTA) content: LTA governs bacterial surface properties and autolysin activity. Mol Microbiol 65:1078–1091PubMedGoogle Scholar
  72. Fitzpatrick F, Humphreys H, O’Gara JP (2005a) Evidence for icaADBC-independent biofilm development mechanism in methicillin-resistant Staphylococcus aureus clinical isolates. J Clin Microbiol 43:1973–1976PubMedGoogle Scholar
  73. Fitzpatrick F, Humphreys H, O’Gara JP (2005b) Evidence for low temperature regulation of biofilm formation in Staphylococcus epidermidis. J Med Microbiol 54:509–510PubMedGoogle Scholar
  74. Flivik G, Sloth M, Rydholm U, Herrlin K, Lidgren L (1993) Technetium-99m-nanocolloid scintigraphy in orthopedic infections: a comparison with indium-111-labeled leukocytes. J Nucl Med 34:1646–1650PubMedGoogle Scholar
  75. Fournier B and Hooper DC (2000) A new two-component regulatory system involved in adhesion, autolysis, and extracellular proteolytic activity of Staphylococcus aureus. J Bacteriol 182:3955–3964PubMedGoogle Scholar
  76. Fournier B and Philpott DJ (2005) Recognition of Staphylococcus aureus by the innate immune system. Clin Microbiol Rev 18:521–540PubMedGoogle Scholar
  77. Fournier B, Klier A, Rapoport G (2001) The two-component system ArlS-ArlR is a regulator of virulence gene expression in Staphylococcus aureus. Mol Microbiol 41:247–261PubMedGoogle Scholar
  78. Fowler SA., Stacy DM, Blackwell HE (2008) Design and synthesis of macrocyclic peptomers as mimics of a quorum sensing signal from Staphylococcus aureus. Org Lett 10:2329–2332PubMedGoogle Scholar
  79. Frees D, Chastanet A, Qazi S, Sorensen K, Hill P, Msadek T, Ingmer H (2004) Clp ATPases are required for stress tolerance, intracellular replication and biofilm formation in Staphylococcus aureus. Mol Microbiol 54:1445–1462PubMedGoogle Scholar
  80. Fuqua WC, Winans SC, Greenberg EP (1994) Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators. J Bacteriol 176:269–275PubMedGoogle Scholar
  81. Gao J and Stewart GC (2004) Regulatory elements of the Staphylococcus aureus protein A (Spa) promoter. J Bacteriol 186:3738–3748PubMedGoogle Scholar
  82. Gomez MI, Lee A, Reddy B, Muir A, Soong G, Pitt A, Cheung A, Prince A (2004) Staphylococcus aureus protein A induces airway epithelial inflammatory responses by activating TNFR1. Nat Med 10:842–848PubMedGoogle Scholar
  83. Goodyear CS and Silverman GJ (2004) Staphylococcal toxin induced preferential and prolonged in vivo deletion of innate-like B lymphocytes. Proc Natl Acad Sci USA 101:11392–11397PubMedGoogle Scholar
  84. Gorman SP, Mawhinney WM, Adair CG, Issouckis M (1993) Confocal laser scanning microscopy of peritoneal catheter surfaces. J Med Microbiol 38:411–417PubMedGoogle Scholar
  85. Gould IM (2005) The clinical significance of methicillin-resistant Staphylococcus aureus. J Hasp Infect 61:277–282Google Scholar
  86. Gristina AG, Oga M, Webb LX, Hobgood CD (1985) Adherent bacterial colonization in the pathogenesis of osteomyelitis. Science 228:990–993PubMedGoogle Scholar
  87. Grundmann H, Ires-de-Sousa M, Boyce J, Tiemersma E (2006) Emergence and resurgence of meticillin-resistant Staphylococcus aureus as a public-health threat. Lancet 368:874–885PubMedGoogle Scholar
  88. Haggar A, Hussain M, Lonnies H, Herrmann M, Norrby-Teglund A, Flock JI (2003) Extracellular adherence protein from Staphylococcus aureus enhances internalization into eukaryotic cells. Infect Immun 71:2310–2317PubMedGoogle Scholar
  89. Hall AE, Domanski PJ, Patel PR, Vernachio JH, Syribeys PJ, Gorovits EL, Johnson MA, Ross JM, Hutchins JT, Patti JM (2003) Characterization of a protective monoclonal antibody recognizing Staphylococcus aureus MSCRAMM protein clumping factor A. Infect Immun 71:6864–6870PubMedGoogle Scholar
  90. Harris LG, Foster SJ, Richards RG (2002) An introduction to Staphylococcus aureus, and techniques for identifying and quantifying S. aureus adhesins in relation to adhesion to biomaterials: review. Eur Cell Mater. 4:39–60PubMedGoogle Scholar
  91. Hebert CK, Williams RE, Levy RS, Barrack RL (1996) Cost of treating an infected total knee replacement. Clin Orthop Relat Res 331:140–145PubMedGoogle Scholar
  92. Hedin H and Larsson S (2004) Technique and considerations when using external fixation as a standard treatment of femoral fractures in children. Injury 35:1255–1263PubMedGoogle Scholar
  93. Heilmann C, Hussain M, Peters G, Gotz F (1997) Evidence for autolysin-mediated primary attachment of Staphylococcus epidermidis to a polystyrene surface. Mol Microbiol 24:1013–1024PubMedGoogle Scholar
  94. Heinrichs JH, Bayer MG, Cheung AL (1996) Characterization of the sar locus and its interaction with agr in Staphylococcus aureus. J Bacteriol 178:418–423PubMedGoogle Scholar
  95. Herrmann M, Vaudaux PE, Pittet D, Auckenthaler R, Lew PD, Schumacher-Perdreau F, Peters G, Waldvogel FA (1988) Fibronectin, fibrinogen, and laminin act as mediators of adherence of clinical staphylococcal isolates to foreign material. J Infect Dis 158:693–701PubMedGoogle Scholar
  96. Herrmann T, Baschieri S, Lees RK, MacDonald HR (1992) In vivo responses of CD4 + and CD8 + cells to bacterial superantigens. Eur J Immunol 22:1935–1938PubMedGoogle Scholar
  97. Hoffman LR, D’Argenio DA, MacCoss MJ, Zhang Z, Jones RA, Miller SI (2005) Aminoglycoside antibiotics induce bacterial biofilm formation. Nature 436:1171–1175PubMedGoogle Scholar
  98. Holland LM, O’Donnell ST, Ryjenkov DA, Gomelsky L, Slater SR, Fey PD, Gomelsky M, O’Gara JP (2008) A staphylococcal GGDEF domain protein regulates biofilm formation independently of cyclic dimeric GMP. J Bacteriol 190:5178–5189PubMedGoogle Scholar
  99. Huang SS and Platt R (2003) Risk of methicillin-resistant Staphylococcus aureus infection after previous infection or colonization. Clin Infect Dis 36:281–285PubMedGoogle Scholar
  100. Hultgren O, Kopf M, Tarkowski A (1999) Outcome of Staphylococcus aureus-triggered sepsis and arthritis in IL-4-deficient mice depends on the genetic background of the host. Eur J Immunol 29:2400–2405PubMedGoogle Scholar
  101. Hussain M, Wilcox MH, White PJ (1993) The slime of coagulase-negative staphylococci: biochemistry and relation to adherence. FEMS Microbiol Rev 10:191–207PubMedGoogle Scholar
  102. Hutson JJJr, Zych GA (1998) Infections in periarticular fractures of the lower extremity treated with tensioned wire hybrid fixators. J Orthop Trauma 12:214–218PubMedGoogle Scholar
  103. Ilizarov GA (1989a) The tension-stress effect on the genesis and growth of tissues. II. The influence of the rate and frequency of distraction. Clin Orthop Relat Res 239:263–285PubMedGoogle Scholar
  104. Ilizarov GA (1989b) The tension-stress effect on the genesis and growth of tissues. I. The influence of stability of fixation and soft-tissue preservation. Clin Orthop Relat Res 238:249–281PubMedGoogle Scholar
  105. Itoh Y, Wang X, Hinnebusch BJ, Preston JFIII, Romeo T (2005) Depolymerization of beta-1,6-N-acetyl-d-glucosamine disrupts the integrity of diverse bacterial biofilms. J Bacteriol 187:382–387PubMedGoogle Scholar
  106. Izano EA, Amarante MA, Kher WB, Kaplan JB (2008) Differential roles of poly-N-acetylglucosamine surface polysaccharide and extracellular DNA in Staphylococcus aureus and Staphylococcus epidermidis biofilms. Appl Environ Microbiol 74:470–476PubMedGoogle Scholar
  107. Jager S, Mack D, Rohde H, Horstkotte MA, Knobloch JK (2005) Disintegration of Staphylococcus epidermidis biofilms under glucose-limiting conditions depends on the activity of the alternative sigma factor {sigma}B. Appl Environ Microbiol 71:5577–5581PubMedGoogle Scholar
  108. Jarraud S, Lyon GJ, Figueiredo AM, Gerard L, Vandenesch F, Etienne J, Muir TW, Novick RP (2000) Exfoliatin-producing strains define a fourth agr specificity group in Staphylococcus aureus. J Bacteriol 182:6517–6522PubMedGoogle Scholar
  109. Jefferson KK, Cramton SE, Gotz F, Pier GB (2003) Identification of a 5-nucleotide sequence that controls expression of the ica locus in Staphylococcus aureus and characterization of the DNA-binding properties of IcaR. Mol Microbiol 48:889–899PubMedGoogle Scholar
  110. 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 186:2449–2456PubMedGoogle Scholar
  111. Jevon M, Guo C, Ma B, Mordan N, Nair SP, Harris M, Henderson B, Bentley G, Meghji S (1999) Mechanisms of internalization of Staphylococcus aureus by cultured human osteoblasts. Infect Immun 67:2677–2681PubMedGoogle Scholar
  112. Ji G, Beavis R, Novick RP (1997) Bacterial interference caused by autoinducing peptide variants. Science 276:2027–2030PubMedGoogle Scholar
  113. Johnson HM, Russell JK, Pontzer CH (1992) Superantigens in human disease. Sci Am 266:92–101PubMedGoogle Scholar
  114. Johnson M, Cockayne A, Morrissey JA (2008) Iron-regulated biofilm formation in Staphylococcus aureus Newman requires ica and the secreted protein Emp. Infect Immun 76:1756–1765PubMedGoogle Scholar
  115. Kaltsas DS (2004) Infection after total hip arthroplasty. Ann R Coll Surg Engl 86:267–271PubMedGoogle Scholar
  116. Kiem S, Oh WS, Peck KR, Lee NY, Lee JY, Song JH, Hwang ES, Kim EC, Cha CY, Choe KW (2004) Phase variation of biofilm formation in Staphylococcus aureus by IS 256 insertion and its impact on the capacity adhering to polyurethane surface. J Korean Med Sci 19:779–782PubMedGoogle Scholar
  117. Kim JH, Kim CH, Hacker J, Ziebuhr W, Lee BK, Cho SH (2008) Molecular characterization of regulatory genes associated with biofilm variation in a Staphylococcus aureus strain. J Microbiol Biotechnol 18:28–34PubMedGoogle Scholar
  118. Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, Harrison LH, Lynfield R, Dumyati G, Townes JM, Craig AS, Zell ER, Fosheim GE, McDougal LK, Carey RB, Fridkin SK (2007) Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA 298:1763–1771PubMedGoogle Scholar
  119. Koch T, Heller S, van AK, Schiefer HG, Neuhof H (1996) Impairment of bacterial clearance induced by norepinephrine infusion in rabbits. Intensive Care Med. 22:637–643PubMedGoogle Scholar
  120. 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 115:688–694PubMedGoogle Scholar
  121. Koenig RL, Ray JL, Maleki SJ, Smeltzer MS, Hurlburt BK (2004) Staphylococcus aureus AgrA binding to the RNAIII-agr regulatory region. J Bacteriol 186:7549–7555PubMedGoogle Scholar
  122. Kourbatova EV, Halvosa JS, King MD, Ray SM, White N, Blumberg HM (2005) Emergence of community-associated methicillin-resistant Staphylococcus aureus USA 300 clone as a cause of health care-associated infections among patients with prosthetic joint infections. Am J Infect Control 33:385–391PubMedGoogle Scholar
  123. Kozitskaya S, Olson ME, Fey PD, Witte W, Ohlsen K, Ziebuhr W (2005) Clonal analysis of Staphylococcus epidermidis isolates carrying or lacking biofilm-mediating genes by multilocus sequence typing. J Clin Microbiol 43:4751–4757PubMedGoogle Scholar
  124. Krakauer T (1995) Differential inhibitory effects of interleukin-10, interleukin-4, and dexamethasone on staphylococcal enterotoxin-induced cytokine production and T cell activation. J Leukoc Biol 57:450–454PubMedGoogle Scholar
  125. 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 36:237–245PubMedGoogle Scholar
  126. Kullik I, Giachino P (1997) The alternative sigma factor sigmaB in Staphylococcus aureus: regulation of the sigB operon in response to growth phase and heat shock. Arch Microbiol 167:151–159PubMedGoogle Scholar
  127. Kwon AS, Park GC, Ryu SY, Lim DH, Lim DY, Choi CH, Park Y, Lim Y (2008) Higher biofilm formation in multidrug-resistant clinical isolates of Staphylococcus aureus. Int J Antimicrob Agents 32:68–72PubMedGoogle Scholar
  128. Lachiewicz PF, Rogers GD, Thomason HC (1996) Aspiration of the hip joint before revision total hip arthroplasty. Clinical and laboratory factors influencing attainment of a positive culture. J Bone Joint Surg Am 78:749–754PubMedGoogle Scholar
  129. Leid JG, Shirtliff ME, Costerton JW, Stoodley AP (2002) Human leukocytes adhere to, penetrate, and respond to Staphylococcus aureus bilfilms. Infect Immun 70:6339–6345PubMedGoogle Scholar
  130. Levitsky KA, Hozack WJ, Balderston RA, Rothman RH, Gluckman SJ, Maslack MM, Booth REJr (1991) Evaluation of the painful prosthetic joint. Relative value of bone scan, sedimentation rate, and joint aspiration. J Arthroplasty 6:237–244PubMedGoogle Scholar
  131. Li H, Xu L, Wang J, Wen Y, Vuong C, Otto M, Gao Q (2005) Conversion of Staphylococcus epidermidis strains from commensal to invasive by expression of the ica locus encoding production of biofilm exopolysaccharide. Infect Immun 73:3188–3191PubMedGoogle Scholar
  132. Liles WC, Thomsen AR, O’Mahony DS, Klebanoff SJ (2001) Stimulation of human neutrophils and monocytes by staphylococcal phenol-soluble modulin. J Leukoc Biol 70:96–102PubMedGoogle Scholar
  133. Lim Y, Jana M, Luong TT, Lee CY (2004) Control of glucose- and NaCl-induced biofilm formation by rbf in Staphylococcus aureus. J Bacteriol 186:722–729PubMedGoogle Scholar
  134. Lina G, Jarraud S, Ji G, Greenland T, Pedraza A, Etienne J, Novick RP, Vandenesch F (1998) Transmembrane topology and histidine protein kinase activity of AgrC, the agr signal receptor in Staphylococcus aureus. Mol Microbiol 28:655–662PubMedGoogle Scholar
  135. Lindsay JA and Holden MT (2004) Staphylococcus aureus: superbug, super genome? Trends Microbiol 12:378–385PubMedGoogle Scholar
  136. Litton MJ, Sander B, Murphy E, O’Garra A, Abrams JS (1994) Early expression of cytokines in lymph nodes after treatment in vivo with Staphylococcus enterotoxin B. J Immunol Methods 175:47–58PubMedGoogle Scholar
  137. Lorenz U, Huttinger C, Schafer T, Ziebuhr W, Thiede A, Hacker J, Engelmann S, Hecker M, Ohlsen K (2008) The alternative sigma factor sigma B of Staphylococcus aureus modulates virulence in experimental central venous catheter-related infections. Microbes Infect 10:217–223PubMedGoogle Scholar
  138. Lyte M, Freestone PP, Neal CP, Olson BA, Haigh RD, Bayston R, Williams PH (2003) Stimulation of Staphylococcus epidermidis growth and biofilm formation by catecholamine inotropes. Lancet 361:130–135PubMedGoogle Scholar
  139. 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 178:175–183PubMedGoogle Scholar
  140. Mahan J, Seligson D, Henry SL, Hynes P, Dobbins J (1991) Factors in pin tract infections. Orthopedics 14:305–308PubMedGoogle Scholar
  141. Maira-Litran T, Kropec A, Abeygunawardana C, Joyce J, Mark GUI, Goldmann DA, Pier GB (2002) Immunochemical properties of the staphylococcal poly-N-acetylglucosamine surface polysaccharide. Infect Immun 70:4433–4440PubMedGoogle Scholar
  142. Majerczyk CD, Sadykov MR, Luong TT, Lee C, Somerville GA, Sonenshein AL (2008) Staphylococcus aureus CodY negatively regulates virulence gene expression. J Bacteriol 190:2257–2265PubMedGoogle Scholar
  143. Manna AC and Cheung AL (2003) sarU, a sarA homolog, is repressed by SarT and regulates virulence genes in Staphylococcus aureus. Infect Immun 71:343–353PubMedGoogle Scholar
  144. Manzotti A, Pullen C, Deromedis B, Catagni MA (2001) Knee arthrodesis after infected total knee arthroplasty using the Ilizarov method. Clin Orthop Relat Res 143–149Google Scholar
  145. Manzotti A, Pullen C, Guerreschi F, Catagni MA (2002) Knee arthrodesis and limb lengthening in the treatment of infected total knee arthroplasty: case report. J Trauma 52:359–363PubMedGoogle Scholar
  146. Mayville P, Ji G, Beavis R, Yang H, Goger M, Novick RP, Muir TW (1999) Structure-activity analysis of synthetic autoinducing thiolactone peptides from Staphylococcus aureus responsible for virulence. Proc Natl Acad Sci USA 96:1218–1223PubMedGoogle Scholar
  147. McNab R, Ford SK, El-Sabaeny A, Barbieri B, Cook GS, Lamont RJ (2003) LuxS-based signaling in Streptococcus gordonii: autoinducer 2 controls carbohydrate metabolism and biofilm formation with Porphyromonas gingivalis. J Bacteriol 185:274–284PubMedGoogle Scholar
  148. McNamara PJ and Proctor RA (2000) Staphylococcus aureus small colony variants, electron transport and persistent infections. Int J Antimicrob Agents 14:117–122PubMedGoogle Scholar
  149. McNamara PJ, Milligan-Monroe KC, Khalili S, Proctor RA (2000) Identification, cloning, and initial characterization of rot, a locus encoding a regulator of virulence factor expression in Staphylococcus aureus. J Bacteriol 182:3197–3203PubMedGoogle Scholar
  150. Mehlin C, Headley CM, Klebanoff SJ (1999) An inflammatory polypeptide complex from Staphylococcus epidermidis: isolation and characterization. J Exp Med 189:907–918PubMedGoogle Scholar
  151. Miethke T, Wahl C, Heeg K, Echtenacher B, Krammer PH, Wagner H (1992) T cell-mediated lethal shock triggered in mice by the superantigen staphylococcal enterotoxin B : critical role of tumor necrosis factor. J Exp Med 175:91–98PubMedGoogle Scholar
  152. Miller MB and Bassler BL (2001) Quorum sensing in bacteria. Annu R v Microbiol 55:165–199Google Scholar
  153. Moran GJ, Krishnadasan A, Gorwitz RJ, Fosheim GE, McDougal LK, Carey RB, Talan DA (2006) Methicillin-resistant S. aureus infections among patients in the emergency department. N Engl J Med 355:666–674PubMedGoogle Scholar
  154. Morfeldt E, Taylor D, von Gabain A, Arvidson S (1995) Activation of alpha-toxin translation in Staphylococcus aureus by the trans-encoded antisense RNA, RNAIII. EMBO J 14:4569–4577PubMedGoogle Scholar
  155. Morfeldt E, Tegmark K, Arvidson S (1996) Transcriptional control of the agr-dependent virulence gene regulator, RNAIII, in Staphylococcus aureus. Mol Microbiol 21:1227–1237PubMedGoogle Scholar
  156. Morrissy RT and Haynes DW (1989) Acute hematogenous osteomyelitis: a model with trauma as an etiology. J Pediatr Orthop 9:447–456PubMedGoogle Scholar
  157. Murai M, Usui A, Seki K, Sakurada J, Masuda S (1992) Intracellular localization of Staphylococcus aureus within primary cultured mouse kidney cells. Microbiol Immunol 36:431–443PubMedGoogle Scholar
  158. Nair SP, Bischoff M, Senn MM, Berger-Bachi B (2003) The sigma B regulon influences internalization of Staphylococcus aureus by osteoblasts. Infect Immun 71:4167–4170PubMedGoogle Scholar
  159. Naudie D, Hamdy RC, Fassier F, Duhaime M (1998) Complications of limb-lengthening in children who have an underlying bone disorder. J Bone Joint Surg Am 80:18–24PubMedGoogle Scholar
  160. Nicholas RO, Li T, McDevitt D, Marra A, Sucoloski S, Demarsh PL, Gentry DR (1999) Isolation and characterization of a sigB deletion mutant of Staphylococcus aureus. Infect Immun 67:3667–3669PubMedGoogle Scholar
  161. Nilsson IM, Hartford O, Foster T, Tarkowski A (1999) Alpha-toxin and gamma-toxin jointly promote Staphylococcus aureus virulence in murine septic arthritis. Infect Immun 67:1045–1049PubMedGoogle Scholar
  162. Novick RP (2003) Autoinduction and signal transduction in the regulation of staphylococcal virulence. Mol Microbiol 48:1429–1449PubMedGoogle Scholar
  163. Novick RP and Jiang D (2003) The staphylococcal saeRS system coordinates environmental signals with agr quorum sensing. Microbiology 149:2709–2717PubMedGoogle Scholar
  164. Novick RP, Ross HF, Projan SJ, Kornblum J, Kreiswirth B, Moghazeh S(1993) Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule. EMBO J 12:3967–3975PubMedGoogle Scholar
  165. Novick RP, Projan SJ, Kornblum J, Ross HF, Ji G, Kreiswirth B, Vandenesch F, Moghazeh S (1995) The agr P2 operon: an autocatalytic sensory transduction system in Staphylococcus aureus. Mol Gen Genet 248:446–458PubMedGoogle Scholar
  166. O’Riordan K and Lee JC (2004) Staphylococcus aureus capsular polysaccharides. Clin Microbiol Rev 17:218–234PubMedGoogle Scholar
  167. Oie S, Huang Y, Kamiya A, Konishi H, Nakazawa T(1996) Efficacy of disinfectants against biofilm cells of methicillin-resistant Staphylococcus aureus. Microbios 85:223–230PubMedGoogle Scholar
  168. Palestro CJ, Roumanas P, Swyer AJ, Kim CK, Goldsmith SJ (1992) Diagnosis of musculoskeletal infection using combined In-111 labeled leukocyte and Tc-99m SC marrow imaging. Clin Nucl Med 17:269–273PubMedGoogle Scholar
  169. Parsons B and Strauss E (2004) Surgical management of chronic osteomyelitis. Am J Surg 188:57–66PubMedGoogle Scholar
  170. Patti JM (2004) A humanized monoclonal antibody targeting Staphylococcus aureus. Vaccine 22 Suppl 1:S39–S43PubMedGoogle Scholar
  171. Pearson JP, Gray KM, Passador L, Tucker KD, Eberhard A, Iglewski BH, Greenberg EP (1994) Structure of the autoinducer required for expression of Pseudomonas aeruginosa virulence genes. Proc Natl Acad Sci USA 91:197–201PubMedGoogle Scholar
  172. Pearson RL and Perry CR (1989) The Ilizarov technique in the treatment of infected tibial nonunions. Orthop Rev 18:609–613PubMedGoogle Scholar
  173. Pechous R, Ledala N, Wilkinson BJ, Jayaswal RK (2004) Regulation of the expression of cell wall stress stimulon member gene msrA1 in methicillin-susceptible or -resistant Staphylococcus aureus. Antimicrob Agents Chemother 48:3057–3063PubMedGoogle Scholar
  174. Pratten J, Foster SJ, Chan PF, Wilson M, Nair SP (2001) Staphylococcus aureus accessory regulators: expression within biofilms and effect on adhesion. Microbes Infect 3:633–637PubMedGoogle Scholar
  175. Qiu R, Pei W, Zhang L, Lin J, Ji G (2005) Identification of the putative staphylococcal AgrB catalytic residues involving the proteolytic cleavage of AgrD to generate autoinducing peptide. J Biol Chem 280:16695–16704PubMedGoogle Scholar
  176. Rachid S, Ohlsen K, Wallner U, Hacker J, Hecker M, Ziebuhr W (2000) Alternative transcription factor sigma(B) is involved in regulation of biofilm expression in a Staphylococcus aureus mucosal isolate. J Bacteriol 182:6824–6826PubMedGoogle Scholar
  177. Radi R, Beckman JS, Bush KM, Freeman BA (1991) Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of Superoxide and nitric oxide. Arch Biochem Biophys 288:481–487PubMedGoogle Scholar
  178. Rani SA, Pitts B, Stewart PS (2005) Rapid diffusion of fluorescent tracers into Staphylococcus epidermidis biofilms visualized by time lapse microscopy. Antimicrob Agents Chemother 49:728–732PubMedGoogle Scholar
  179. Rani SA, Pitts B, Beyenal H, Veluchamy RA, Lewandowski Z, Davison WM, Buckingham-Meyer K, Stewart PS (2007) Spatial patterns of DNA replication, protein synthesis, and oxygen concentration within bacterial biofilms reveal diverse physiological states. J Bacteriol 189:4223–4233PubMedGoogle Scholar
  180. Recsei P, Kreiswirth B, O’Reilly M, Schlievert P, Grass A, Novick RP (1986) Regulation of exoprotein gene expression in Staphylococcus aureus by agr. Mol Gen Genet 202:58–61PubMedGoogle Scholar
  181. Resch A, Rosenstein R, Nerz C, Gotz F (2005) Differential gene expression profiling of Staphylococcus aureus cultivated under biofilm and planktonic conditions. Appl Environ Microbiol 71:2663–2676PubMedGoogle Scholar
  182. Rice KC, Mann EE, Endres JL, Weiss EC, Cassat JE, Smeltzer MS, Bayles KW (2007) The cidA murein hydrolase regulator contributes to DNA release and biofilm development in Staphylococcus aureus. Proc Natl Acad Sci USA 104:8113–8118PubMedGoogle Scholar
  183. Richardson AR, Libby SJ, Fang FC (2008) A nitric oxide-inducible lactate dehydrogenase enables Staphylococcus aureus to resist innate immunity. Science 319:1672–1676PubMedGoogle Scholar
  184. Ring D, Jupiter JB, Labropoulos PK, Guggenheim JJ, Stanitsky DF, Spencer DM (1996) Treatment of deformity of the lower limb in adults who have osteogenesis imperfecta. J Bone Joint Surg Am 78:220–225PubMedGoogle Scholar
  185. Roberts P, Walters AJ, McMinn DJ (1992) Diagnosing infection in hip replacements. The use of fine-needle aspiration and radiometric culture. J Bone Joint Surg Br 74:265–269PubMedGoogle Scholar
  186. 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 55:1883–1895PubMedGoogle Scholar
  187. Rothfork JM, Ssus-Babus S, Van Wamel WJ, Cheung AL, Gresham HD (2003) Fibrinogen depletion attenuates Staphyloccocus aureus infection by preventing density-dependent virulence gene up-regulation. J Immunol 171:5389–5395PubMedGoogle Scholar
  188. Rothfork JM, Timmins GS, Harris MN, Chen X, Lusis AJ, Otto M, Cheung AL, Gresham HD (2004) Inactivation of a bacterial virulence pheromone by phagocyte-derived oxidants: new role for the NADPH oxidase in host defense. Proc Natl Acad Sci USA 101:13867–13872PubMedGoogle Scholar
  189. Ruoslahti E (1996) RGD and other recognition sequences for integrins. Annu Rev Cell Dev Biol 12:697–715PubMedGoogle Scholar
  190. Rupp CJ, Fux CA, Stoodley P (2005) Viscoelasticity of Staphylococcus aureus biofilms in response to fluid shear allows resistance to detachment and facilitates rolling migration. Appl Environ Microbiol 71:2175–2178PubMedGoogle Scholar
  191. Sadovskaya I, Vinogradov E, Flahaut S, Kogan G, Jabbouri S (2005) Extracellular carbohydrate-containing polymers of a model biofilm-producing strain, Staphylococcus epidermidis RP62A. Infect Immun 73:3007–3017PubMedGoogle Scholar
  192. Saenz HL, Augsburger V, Vuong C, Jack RW, Gotz F, Otto M (2000) Inducible expression and cellular location of AgrB, a protein involved in the maturation of the staphylococcal quorumsensing pheromone. Arch Microbiol 174:452–455PubMedGoogle Scholar
  193. Saldanha KA, Saleh M, Bell MJ, Fernandes JA (2004) Limb lengthening and correction of deformity in the lower limbs of children with osteogenesis imperfecta. J Bone Joint Surg Br 86:259–265PubMedGoogle Scholar
  194. Sanzen L and Carlsson AS (1989) The diagnostic value of C-reactive protein in infected total hip arthroplasties. J Bone Joint Surg Br 71:638–641PubMedGoogle Scholar
  195. Sasaki S, Nishikawa S, Miura T, Mizuki M, Yamada K, Madarame H, Tagawa YI, Iwakura Y, Nakane A (2000) Interleukin-4 and interleukin-10 are involved in host resistance to Staphylococcus aureus infection through regulation of gamma interferon. Infect Immun 68:2424–2430PubMedGoogle Scholar
  196. Sauer K, Camper AK, Ehrlich GD, Costerton JW, Davies DG (2002) Pseudomonas aeruginosa displays multiple phenotypes during development as a biofilm. J Bacteriol 184:1140–1154PubMedGoogle Scholar
  197. Scott RJ, Lian LY, Muharram SH, Cockayne A, Wood SJ, Bycroft BW, Williams P, Chan WC (2003) Side-chain-to-tail thiolactone peptide inhibitors of the staphylococcal quorum-sensing system. Bioorg Med Chem Lett 13:2449–2453PubMedGoogle Scholar
  198. Segawa H, Tsukayama DT, Kyle RF, Becker DA, Gustilo RB (1999) Infection after total knee arthroplasty. A retrospective study of the treatment of eighty-one infections. J Bone Joint Surg Am 81:1434–1445PubMedGoogle Scholar
  199. Seidl K, Goerke C, Wolz C, Mack D, Berger-Bachi B, Bischoff M (2008) Staphylococcus aureus CcpA affects biofilm formation. Infect Immun 76:2044–2050PubMedGoogle Scholar
  200. Seol JH, Yoo SJ, Shin DH, Shim YK, Kang MS, Goldberg AL, Chung CH (1997) The heat-shock protein HslVU from Escherichia coli is a protein-activated ATPase as well as an ATP-dependent proteinase. Eur J Biochem 247:1143–1150PubMedGoogle Scholar
  201. Shanks RM, Donegan NP, Graber ML, Buckingham SE, Zegans ME, Cheung AL, O’Toole GA (2005) Heparin stimulates Staphylococcus aureus biofilm formation. Infect Immun 73:4596–4606PubMedGoogle Scholar
  202. Shenkman B, Varon D, Tamarin I, Dardik R, Peisachov M, Savion N, Rubinstein E (2002) Role of agr (RNAIII) in Staphylococcus aureus adherence to fibrinogen, fibronectin, platelets and endothelial cells under static and flow conditions. J Med Microbiol 51:747–754PubMedGoogle Scholar
  203. Shih LY, Wu JJ, Yang DJ (1987) Erythrocyte sedimentation rate and C-reactive protein values in patients with total hip arthroplasty. Clin Orthop Relat Res 238–246Google Scholar
  204. Shirtliff ME, Mader JT, Camper AK (2002) Molecular interactions in biofilms. Chem Biol 9:859–871PubMedGoogle Scholar
  205. Silverman GJ, Goodyear CS, Siegel DL (2005) On the mechanism of staphylococcal protein A immunomodulation. Transfusion 45:274–280PubMedGoogle Scholar
  206. Simonetti O, Cirioni O, Ghiselli R, Goteri G, Scalise A, Orlando F, Silvestri C, Riva A, Saba V, Madanahally KD, Offidani A, Balaban N, Scalise G, Giacometti A (2008) RNAIII-inhibiting peptide enhances healing of wounds infected with methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 52:2205–2211PubMedGoogle Scholar
  207. Sinha B, Francois PP, Nusse O, Foti M, Hartford OM, Vaudaux P, Foster TJ, Lew DP, Herrmann M, Krause KH (1999) Fibronectin-binding protein acts as Staphylococcus aureus invasin via fibronectin bridging to integrin alpha5beta1. Cell Microbiol 1:101–117PubMedGoogle Scholar
  208. Siqueira JA, Speeg-Schatz C, Freitas FI, Sahel J, Monteil H, Prevost G (1997) Channel-forming leucotoxins from Staphylococcus aureus cause severe inflammatory reactions in a rabbit eye model. J Med Microbiol 46:486–494PubMedGoogle Scholar
  209. Song HR, Cho SH, Koo KH, Jeong ST, Park YJ, Ko JH (1998) Tibial bone defects treated by internal bone transport using the Ilizarov method. Int Orthop 22:293–297PubMedGoogle Scholar
  210. Sonmezoglu K, Sonmezoglu M, Halac M, Akgun I, Turkmen C, Onsel C, Kanmaz B, Solanki K, Britton KE, Uslu I (2001) Usefulness of 99mTc-ciprofloxacin (infecton) scan in diagnosis of chronic orthopedic infections: comparative study with 99mTc-HMPAO leukocyte scintigraphy. J Nucl Med 42:567–574PubMedGoogle Scholar
  211. Spangehl MJ, Masri BA, O’Connell JX, Duncan CP (1999) Prospective analysis of preoperative and intraoperative investigations for the diagnosis of infection at the sites of two hundred and two revision total hip arthroplasties. J Bone Joint Surg Am 81:672–683PubMedGoogle Scholar
  212. Sperandio V, Torres AG, Jarvis B, Nataro JP, Kaper JB (2003) Bacteria-host communication: the language of hormones. Proc Natl Acad Sci USA 100:8951–8956PubMedGoogle Scholar
  213. Spoering AL and Lewis K (2001) Biofilms and planktonic cells of Pseudomonas aeruginosa have similar resistance to killing by antimicrobials. J Bacteriol 183:6746–6751PubMedGoogle Scholar
  214. Stoodley P, Kathju S, Hu FZ, Erdos G, Levenson JE, Mehta N, Dice B, Johnson S, Hall-Stoodley L, Nistico L, Sotereanos N, Sewecke J, Post JC, Ehrlich GD (2005) Molecular and imaging techniques for bacterial biofilms in joint arthroplasty infections. Clin Orthop Relat Res 31–40Google Scholar
  215. Sun D, Accavitti MA, Bryers JD (2005) Inhibition of biofilm formation by monoclonal antibodies against Staphylococcus epidermidis RP62A accumulation-associated protein. Clin Diagn Lab Immunol 12:93–100PubMedGoogle Scholar
  216. Sun J, Daniel R, Wagner-Dobler I, Zeng AP (2004) Is autoinducer-2 a universal signal for interspecies communication: a comparative genomic and phylogenetic analysis of the synthesis and signal transduction pathways. BMC Evol Biol 4:36PubMedGoogle Scholar
  217. Teller RE, Christie MJ, Martin W, Nance EP, Haas DW (2000) Sequential indium-labeled leukocyte and bone scans to diagnose prosthetic joint infection. Clin Orthop Relat Res 241–247Google Scholar
  218. Thoren B and Wigren A (1991) Erythrocyte sedimentation rate in infection of total hip replacements. Orthopedics 14:495–497PubMedGoogle Scholar
  219. Toledo-Arana A, Merino N, Vergara-Irigaray M, Debarbouille M, Penades JR, Lasa I (2005) Staphylococcus aureus develops an alternative, ica-independent biofilm in the absence of the arlRS two-component system. J Bacteriol 187:5318–5329PubMedGoogle Scholar
  220. Tomak Y, Kocaoglu M, Piskin A, Yildiz C, Gulman B, Tomak L (2005) Treatment of intertro-chanteric fractures in geriatric patients with a modified external fixator. Injury 36:635–643PubMedGoogle Scholar
  221. Tormo MA, Knecht E, Gotz F, Lasa I, Penades JR (2005a) Bap-dependent biofilm formation by pathogenic species of Staphylococcus: evidence of horizontal gene transfer? Microbiology 151:2465–2475PubMedGoogle Scholar
  222. Tormo MA, Marti M, Valle J, Manna AC, Cheung AL, Lasa I, Penades JR (2005b) SarA is an essential positive regulator of Staphylococcus epidermidis biofilm development. J Bacteriol 187:2348–2356PubMedGoogle Scholar
  223. Trampuz A and Zimmerli W (2005) Prosthetic joint infections: update in diagnosis and treatment. Swiss Med Wkly 135:243–251PubMedGoogle Scholar
  224. Trotonda MP, Manna AC, Cheung AL, Lasa I, Penades JR (2005) SarA positively controls bap-dependent biofilm formation in Staphylococcus aureus. J Bacteriol 187:5790–5798PubMedGoogle Scholar
  225. Tzianabos AO, Wang JY, Lee JC (2001) Structural rationale for the modulation of abscess formation by Staphylococcus aureus capsular polysaccharides. Proc Natl Acad Sci USA 98:9365–9370PubMedGoogle Scholar
  226. Valle J, Toledo-Arana A, Berasain C, Ghigo JM, Amorena B, Penades JR, Lasa I (2003) SarA and not sigmaB is essential for biofilm development by Staphylococcus aureus. Mol Microbiol 48:1075–1087PubMedGoogle Scholar
  227. Valle J, Vergara-Irigaray M, Merino N, Penades JR, Lasa I (2007) sigmaB regulates IS256-mediated Staphylococcus aureus biofilm phenotypic variation. J Bacteriol 189:2886–2896PubMedGoogle Scholar
  228. Van Wamel WJ, van Rossum G, Verhoef J, Vandenbroucke-Grauls CM, Fluit AC (1998) Cloning and characterization of an accessory gene regulator (agr)-like locus from Staphylococcus epidermidis. FEMS Microbiol Lett 163:1–9PubMedGoogle Scholar
  229. Vandecasteele SJ, Peetermans WE, Merckx R, Rijnders BJ, Van EJ (2003) Reliability of the ica, aap and atlE genes in the discrimination between invasive, colonizing and contaminant Staphylococcus epidermidis isolates in the diagnosis of catheter-related infections. Clin Microbiol Infect 9:114–119PubMedGoogle Scholar
  230. Vautor E, Abadie G, Pont A, Thiery R (2008) Evaluation of the presence of the bap gene in Staphylococcus aureus isolates recovered from human and animals species. Vet Microbiol 127:407–411PubMedGoogle Scholar
  231. Vernachio J, Bayer AS, Le T, Chai YL, Prater B, Schneider A, Ames B, Syribeys P, Robbins J, Patti JM (2003) Anti-clumping factor A immunoglobulin reduces the duration of methicillin-resistant Staphylococcus aureus bacteremia in an experimental model of infective endocarditis. Antimicrob Agents Chemother 47:3400–3406PubMedGoogle Scholar
  232. Visai L, Xu Y, Casolini F, Rindi S, Hook M, Speziale P (2000) Monoclonal antibodies to CNA, a collagen-binding microbial surface component recognizing adhesive matrix molecules, detach Staphylococcus aureus from a collagen substrate. J Biol Chem 275:39837–39845PubMedGoogle Scholar
  233. Vlisidou I, Lyte M, van Diemen PM, Hawes P, Monaghan P, Wallis TS, Stevens MP (2004) The neuroendocrine stress hormone norepinephrine augments Escherichia coli O157:H7-induced enteritis and adherence in a bovine ligated ileal loop model of infection. Infect Immun 72:5446–5451PubMedGoogle Scholar
  234. Vuong C, Gerke C, Somerville GA, Fischer ER, Otto M (2003) Quorum-sensing control of biofilm factors in Staphylococcus epidermidis. J Infect Dis 188:706–718PubMedGoogle Scholar
  235. Vuong C, Durr M, Carmody AB, Peschel A, Klebanoff SJ, Otto M (2004a) Regulated expression of pathogen-associated molecular pattern molecules in Staphylococcus epidermidis: quorumsensing determines pro-inflammatory capacity and production of phenol-soluble modulins. Cell Microbiol 6:753–759PubMedGoogle Scholar
  236. Vuong C, Kocianova S, Voyich JM, Yao Y, Fischer ER, DeLeo FR, Otto M (2004b) A crucial role for exopolysaccharide modification in bacterial biofilm formation, immune evasion, and virulence. J Biol Chem 279:54881–54886PubMedGoogle Scholar
  237. Vuong C, Kocianova S, Yao Y, Carmody AB, Otto M (2004c) Increased colonization of indwelling medical devices by quorum-sensing mutants of Staphylococcus epidermidis in vivo. J Infect Dis 190:1498–1505PubMedGoogle Scholar
  238. Vuong C, Kidder JB, Jacobson ER, Otto M, Proctor RA, Somerville GA (2005) Staphylococcus epidermidis polysaccharide intercellular adhesin production significantly increases during tricarboxylic acid cycle stress. J Bacteriol 187:2967–2973PubMedGoogle Scholar
  239. 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 182:1688–1693PubMedGoogle Scholar
  240. Vuong C, Voyich JM, Fischer ER, Braughton KR, Whitney AR, DeLeo FR, Otto M (2004) Polysaccharide intercellular adhesin (PIA) protects Staphylococcus epidermidis against major components of the human innate immune system. Cell Microbiol 6:269–275PubMedGoogle Scholar
  241. Waldvogel FA, Medoff G, Swartz MN (1970a) Osteomyelitis: a review of clinical features, therapeutic considerations and unusual aspects (third of three parts). Osteomyelitis associated with vascular insufficiency. N Engl J Med 282:316–322PubMedGoogle Scholar
  242. Waldvogel FA, Medoff G, Swartz MN (1970b) Osteomyelitis: a review of clinical features, therapeutic considerations and unusual aspects (second of three parts). N Engl J Med 282:260–266PubMedGoogle Scholar
  243. Waldvogel FA, Medoff G, Swartz MN (1970c) Osteomyelitis: a review of clinical features, therapeutic considerations and unusual aspects. N Engl J Med 282:198–206PubMedGoogle Scholar
  244. Watts A, Ke D, Wang Q, Pillay A, Nicholson-Weller A, Lee JC (2005) Staphylococcus aureus strains that express serotype 5 or serotype 8 capsular polysaccharides differ in virulence. Infect Immun 73:3502–3511PubMedGoogle Scholar
  245. Wesson CA, Liou LE, Todd KM, Bohach GA, Trumble WR, Bayles KW (1998) Staphylococcus aureus Agr and Sar global regulators influence internalization and induction of apoptosis. Infect Immun 66:5238–5243PubMedGoogle Scholar
  246. Williams RJ, Henderson B, Nair SP (2002) Staphylococcus aureus fibronectin binding proteins A and B possess a second fibronectin binding region that may have biological relevance to bone tissues. Calcif Tissue Int 70:416–421PubMedGoogle Scholar
  247. Wink DA, Kasprzak KS, Maragos CM, Elespuru RK, Misra M, Dunams TM, Cebula TA, Koch WH, Andrews AW, Allen JS (1991) DNA deaminating ability and genotoxicity of nitric oxide and its progenitors. Science 254:1001–1003PubMedGoogle Scholar
  248. Winzer K, Hardie KR, Williams P (2002) Bacterial cell-to-cell communication: sorry, can’t talk now — gone to lunch! Curr Opin Microbiol 5:216–222PubMedGoogle Scholar
  249. Wolz C, Pohlmann-Dietze P, Steinhuber A, Chien YT, Manna A, van Wamel W, Cheung A (2000) Agr-independent regulation of fibronectin-binding protein(s) by the regulatory locus sar in Staphylococcus aureus. Mol Microbiol 36:230–243PubMedGoogle Scholar
  250. Wright JSIII, Lyon GJ, George EA, Muir TW, Novick RP (2004) Hydrophobic interactions drive ligand-receptor recognition for activation and inhibition of staphylococcal quorum sensing. Proc Natl Acad Sci USA 101:16168–16173PubMedGoogle Scholar
  251. Wright JSIII, Jin R, Novick RP (2005) Transient interference with staphylococcal quorum sensing blocks abscess formation. Proc Natl Acad Sci USA 102:1691–1696PubMedGoogle Scholar
  252. Xu KD, McFeters GA, Stewart PS (2000) Biofilm resistance to antimicrobial agents. Microbiology 146:547–549PubMedGoogle Scholar
  253. 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 191:289–298PubMedGoogle Scholar
  254. Yarwood JM, Schlievert PM (2003) Quorum sensing in Staphylococcus infections. J Clin Invest 112:1620–1625PubMedGoogle Scholar
  255. Yarwood JM, Bartels DJ, Volper EM, Greenberg EP (2004) Quorum sensing in Staphylococcus aureus biofilms. J Bacteriol 186:1838–1850PubMedGoogle Scholar
  256. Yarwood JM, Paquette KM, Tikh IB, Volper EM, Greenberg EP (2007) Generation of virulence factor variants in Staphylococcus aureus biofilms. J Bacteriol 189:7961–7967PubMedGoogle Scholar
  257. Yoon KS, Fitzgerald RHJ, Sud S, Song Z, Wooley PH (1999) Experimental acute hematogenous osteomyelitis in mice. II. Influence of Staphylococcus aureus infection on T-cell immunity. J Orthop Res 17:382–391PubMedGoogle Scholar
  258. Zhang L, Ji G (2004) Identification of a staphylococcal AgrB segment(s) responsible for group-specific processing of AgrD by gene swapping. J Bacteriol 186:6706–6713PubMedGoogle Scholar
  259. Zhang L, Gray L, Novick RP, Ji G (2002) Transmembrane topology of AgrB, the protein involved in the post-translational modification of AgrD in Staphylococcus aureus. J Biol Chem 277:34736–34742PubMedGoogle Scholar
  260. Zhang L, Lin J, Ji G (2004) Membrane anchoring of the AgrD N-terminal amphipathic region is required for its processing to produce a quorum-sensing pheromone in Staphylococcus aureus. J Biol Chem 279:19448–19456PubMedGoogle Scholar
  261. Zimmerli W, Ochsner PE (2003) Management of infection associated with prosthetic joints. Infection 31:99–108PubMedGoogle Scholar
  262. Zimmerli W, Trampuz A, Ochsner PE (2004) Prosthetic-joint infections. N Engl J Med 351:1645–1654PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  1. 1.Department of Biomedical Sciences, Dental SchoolUniversity of Maryland-BaltimoreBaltimoreUSA
  2. 2.Center for Microbial Genetics and Genomics, Department of Biological SciencesNorthern Arizona UniversityFlagstaffUSA

Personalised recommendations