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  • Review Article
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Implant infections: adhesion, biofilm formation and immune evasion

Abstract

Medical device-associated infections account for a large proportion of hospital-acquired infections. A variety of opportunistic pathogens can cause implant infections, depending on the type of the implant and on the anatomical site of implantation. The success of these versatile pathogens depends on rapid adhesion to virtually all biomaterial surfaces and survival in the hostile host environment. Biofilm formation on implant surfaces shelters the bacteria and encourages persistence of infection. Furthermore, implant-infecting bacteria can elude innate and adaptive host defences as well as biocides and antibiotic chemotherapies. In this Review, we explore the fundamental pathogenic mechanisms underlying implant infections, highlighting orthopaedic implants and Staphylococcus aureus as a prime example, and discuss innovative targets for preventive and therapeutic strategies.

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Fig. 1: Adhesion of Staphylococcus aureus to implant surfaces.
Fig. 2: Stages of staphylococcal biofilm formation.
Fig. 3: Immune evasion by Staphylococcus aureus.

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References

  1. Arciola, C. R., Campoccia, D., Ehrlich, G. D. & Montanaro, L. Biofilm-based implant infections in orthopaedics. Adv. Exp. Med. Biol. 830, 29–46 (2015).

    Article  PubMed  Google Scholar 

  2. Montanaro, L. et al. Scenery of Staphylococcus implant infections in orthopedics. Future Microbiol. 6, 1329–1349 (2011).

    Article  CAS  PubMed  Google Scholar 

  3. Magill, S. S. et al. Emerging infections program healthcare-associated infections and antimicrobial use prevalence survey team. Multistate point-prevalence survey of health care-associated infections. N. Engl. J. Med. 370, 1198–1208 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Arciola, C. R., An, Y. H., Campoccia, D., Donati, M. E. & Montanaro, L. Etiology of implant orthopedic infections: a survey on 1027 clinical isolates. Int. J. Artif. Organs. 28, 1091–1100 (2005).

    Article  CAS  PubMed  Google Scholar 

  5. Anderson, J. M. Future challenges in the in vitro and in vivo evaluation of biomaterial biocompatibility. Regen. Biomater. 3, 73–77 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Menkin, V. Studies on inflammation: VII. Fixation of bacteria and of particulate matter at the site of inflammation. J. Exp. Med. 53, 647–660 (1931).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Gristina, A. G. Implant failure and the immuno-incompetent fibroinflammatory zone. Clin. Orthop. Relat. Res. 298, 106–118 (1994).

    Article  Google Scholar 

  8. Schierholz, J. M. & Beuth, J. Implant infections: a haven for opportunistic bacteria. J. Hosp. Infect. 49, 87–93 (2001).

    Article  CAS  PubMed  Google Scholar 

  9. Arciola, C. R., Campoccia, D., Speziale, P., Montanaro, L. & Costerton, J. W. Biofilm formation in Staphylococcus implant infections. A review of molecular mechanisms and implications for biofilm-resistant materials. Biomaterials 33, 5967–5982 (2012). This article reviews the formation and composition of biofilms on biomaterials and anti-biofilm biomaterials.

    Article  CAS  PubMed  Google Scholar 

  10. Southwood, R. T. et al. Infection in experimental hip arthroplasties. J. Bone Joint Surg. Br. 67, 229–231 (1985).

    Article  CAS  PubMed  Google Scholar 

  11. von Eiff, C., Arciola, C. R., Montanaro, L., Becker, K. & Campoccia, D. Emerging Staphylococcus species as new pathogens in implant infections. Int. J. Artif. Organs. 29, 360–367 (2003).

    Article  Google Scholar 

  12. Zimmerli, W. Clinical presentation and treatment of orthopaedic implant-associated infection. J. Intern. Med. 276, 111–119 (2014). This article discusses old and new criteria for the classification of periprosthetic joint infections.

    Article  CAS  PubMed  Google Scholar 

  13. Osmon, D. R. et al. Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the infectious diseases society of America. Clin. Infect. Dis. 56, e1–e25 (2013).

    Article  PubMed  Google Scholar 

  14. Tande, A. J. & Patel, R. Prosthetic joint infection. Clin. Microbiol. Rev. 27, 302–345 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Cobo, J. & Del Pozo, J. L. Prosthetic joint infection: diagnosis and management. Expert. Rev. Anti Infect. Ther. 9, 787–802 (2011).

    Article  PubMed  Google Scholar 

  16. Campoccia, D., Montanaro, L. & Arciola, C. R. A review of the clinical implications of anti-infective biomaterials and infection-resistant surfaces. Biomaterials 34, 8018–8029 (2013).

    Article  CAS  PubMed  Google Scholar 

  17. Trampuz, A. & Widmer, A. F. Infections associated with orthopedic implants. Curr. Opin. Infect. Dis. 19, 349–356 (2006).

    Article  CAS  PubMed  Google Scholar 

  18. Aggarwal, V. K. et al. Organism profile in periprosthetic joint infection: pathogens differ at two arthroplasty infection referral centers in Europe and in the United States. J. Knee Surg. 27, 399–406 (2014).

    Article  PubMed  Google Scholar 

  19. Campoccia, D., Montanaro, L. & Arciola, C. R. The significance of infection related to orthopedic devices and issues of antibiotic resistance. Biomaterials 27, 2331–2339 (2006).

    Article  CAS  PubMed  Google Scholar 

  20. Li, B. & Webster, T. J. Bacteria antibiotic resistance: new challenges and opportunities for implant-associated orthopedic infections. J. Orthop. Res. 36, 22–32 (2018).

    PubMed  Google Scholar 

  21. Guo, G., Wang, J., You, Y., Tan, J. & Shen, H. Distribution characteristics of Staphylococcus spp. in different phases of periprosthetic joint infection: a review. Exp. Ther. Med. 13, 2599–2608 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Campoccia, D. et al. Cluster analysis of ribotyping profiles of Staphylococcus epidermidis isolates recovered from foreign body-associated orthopedic infections. J. Biomed. Mater. Res. A. 88, 664–672 (2009).

    Article  PubMed  CAS  Google Scholar 

  23. Campoccia, D. et al. Molecular epidemiology of Staphylococcus aureus from implant orthopaedic infections: ribotypes, agr polymorphism, leukocidal toxins and antibiotic resistance. Biomaterials 29, 4108–4116 (2008).

    Article  CAS  PubMed  Google Scholar 

  24. An, Y. H. Dickinson, R. B. & Doyle, R. J. in Handbook of bacterial adhesion: principles, methods, and applications (eds An, Y. H. & Friedman, R. J.) 1–27 (Humana Press, 2000).

  25. Dunne, W. M. Jr. Bacterial adhesion: seen any good biofilms lately? Clin. Microbiol. Rev. 15, 155–166 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Franz, S., Rammelt, S., Scharnweber, D. & Simon, J. C. Immune responses to implants - a review of the implications for the design of immunomodulatory biomaterials. Biomaterials 32, 6692–6709 (2011).

    Article  CAS  PubMed  Google Scholar 

  27. Speziale, P. et al. Structural and functional role of Staphylococcus aureus surface components recognizing adhesive matrix molecules of the host. Future Microbiol. 4, 1337–1352 (2009).

    Article  CAS  PubMed  Google Scholar 

  28. Wilson, C. J., Clegg, R. E., Leavesley, D. I. & Pearcy, M. J. Mediation of biomaterial-cell interactions by adsorbed proteins: a review. Tissue Eng. 11, 1–18 (2005).

    Article  CAS  PubMed  Google Scholar 

  29. Otto, M. Staphylococcus epidermidis — the ‘accidental’ pathogen. Nat. Rev. Microbiol. 7, 555–567 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Paharik, A. E. & Horswill, A. R. The Staphylococcal biofilm: adhesins, regulation, and host response. Microbiol. Spectr. 4, 2 (2016).

    Article  CAS  Google Scholar 

  31. Bos, R., van der Mei, H. C. & Busscher, H. J. Physico-chemistry of initial microbial adhesive interactions — its mechanisms and methods for study. FEMS Microbiol. Rev. 23, 179–230 (1999).

    Article  CAS  PubMed  Google Scholar 

  32. Ribeiro, M., Monteiro, F. J. & Ferraz, M. P. Infection of orthopedic implants with emphasis on bacterial adhesion process and techniques used in studying bacterial-material interactions. Biomatter 2, 176–194 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  33. Nguyen, V. T., Chia, T. W., Turner, M. S., Fegan, N. & Dykes, G. A. Quantification of acid-base interactions based on contact angle measurement allows XDLVO predictions to attachment of Campylobacter jejuni but not Salmonella. J. Microbiol. Methods. 86, 89–96 (2011).

    Article  CAS  PubMed  Google Scholar 

  34. Perni, S., Preedy, E. C. & Prokopovich, P. Success and failure of colloidal approaches in adhesion of microorganisms to surfaces. Adv. Colloid Interface Sci. 206, 265–274 (2014).

    Article  CAS  PubMed  Google Scholar 

  35. Kline, K. A., Fälker, S., Dahlberg, S., Normark, S. & Henriques-Normark, B. Bacterial adhesins in host-microbe interactions. Cell Host Microbe. 5, 580–592 (2009).

    Article  CAS  PubMed  Google Scholar 

  36. Mandlik, A., Swierczynski, A., Das, A. & Ton-That, H. Pili in grampositive bacteria: assembly, involvement in colonization and biofilm development. Trends Microbiol. 16, 33–40 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Katsutoshi, H. & Shinya, M. Bacterial adhesion: from mechanism to control. Biochem. Eng. J. 48, 424–434 (2010).

    Article  CAS  Google Scholar 

  38. Heilmann, C., Hussain, M., Peters, G. & Götz, F. Evidence for autolysin-mediated primary attachment of Staphylococcus epidermidis to a polystyrene surface. Mol. Microbiol. 24, 1013–1024 (1997).

    Article  CAS  PubMed  Google Scholar 

  39. Foster, S. J. Molecular characterization and functional analysis of the major autolysin of Staphylococcus aureus 8325/4. J. Bacteriol. 177, 5723–5725 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Bose, J. L., Lehman, M. K., Fey, P. D. & Bayles, K. W. Contribution of the Staphylococcus aureus Atl AM and GL murein hydrolase activities in cell division, autolysis, and biofilm formation. PLoS ONE. 7, e42244 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Hirschhausen, N. et al. A novel staphylococcal internalization mechanism involves the major autolysin Atl and heat shock cognate protein Hsc70 as host cell receptor. Cell. Microbiol. 12, 1746–1764 (2010).

    Article  CAS  PubMed  Google Scholar 

  42. Mohamed, J. A., Huang, W., Nallapareddy, S. R., Teng, F. & Murray, B. E. Influence of origin of isolates, especially endocarditis isolates, and various genes on biofilm formation by Enterococcus faecalis. Infect. Immun. 72, 3658–3663 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Boland, T., Latour, R. A. & Stutzenberger, F. J. in Handbook of bacterial adhesion: principles, methods, and applications (eds An, Y. H. & Friedman, R. J.) 1–27 (Humana Press, 2000).

  44. Patti, J. M., Allen, B. L., McGavin, M. J. & Höök, M. MSCRAMM-mediated adherence of microorganisms to host tissues. Annu. Rev. Microbiol. 48, 585–617 (1994).

    Article  CAS  PubMed  Google Scholar 

  45. Chavakis, T., Wiechmann, K., Preissner, K. T. & Herrmann, M. Staphylococcus aureus interactions with the endothelium: the role of bacterial “secretable expanded repertoire adhesive molecules” (SERAM) in disturbing host defense systems. Thromb. Haemost. 94, 278–285 (2005).

    CAS  PubMed  Google Scholar 

  46. Foster, T. J., Geoghegan, J. A., Ganesh, V. K. & Höök, M. Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus. Nat. Rev. Microbiol. 12, 49–62 (2014). This review presents the structural and functional properties of MSCRAMMs.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Campoccia, D. et al. The presence of both bone sialoprotein-binding protein gene and collagen adhesin gene as a typical virulence trait of the major epidemic cluster in isolates from orthopedic implant infections. Biomaterials. 30, 6621–6628 (2009).

    Article  CAS  PubMed  Google Scholar 

  48. Mao, Y. & Schwarzbauer, J. E. Fibronectin fibrillogenesis, a cell-mediated matrix assembly process. Matrix Biol. 24, 389–399 (2005).

    Article  CAS  PubMed  Google Scholar 

  49. Arciola, C. R. et al. Staphylococcus epidermidis-fibronectin binding and its inhibition by heparin. Biomaterials 24, 3013–3019 (2003).

    Article  CAS  PubMed  Google Scholar 

  50. Arciola, C. R., Campoccia, D., Gamberini, S., Donati, M. E. & Montanaro, L. Presence of fibrinogen-binding adhesin gene in Staphylococcus epidermidis isolates from central venous catheters-associated and orthopaedic implant-associated infections. Biomaterials 25, 4825–4829 (2004).

    Article  CAS  PubMed  Google Scholar 

  51. Gristina, A. G., Naylor, P. & Myrvik, Q. Infections from biomaterials and implants: a race for the surface. Med. Prog. Technol. 14, 205–224 (1988–1989).

    PubMed  Google Scholar 

  52. Subbiahdoss, G., Kuijer, R., Grijpma, D. W., van der Mei, H. C. & Busscher, H. J. Microbial biofilm growth versus tissue integration: “the race for the surface” experimentally studied. Acta Biomater 5, 1399–1404 (2009). The fate of biomaterial implants depends on the balance between integration by host cells and tissues and bacterial colonization, and this paper studies this competition with an interesting experimental approach.

    CAS  Google Scholar 

  53. Gristina, A. G. Biomaterial-centered infection: microbial adhesion versus tissue integration. Science 237, 1588–1595 (1987).

    Article  CAS  PubMed  Google Scholar 

  54. Stones, D. H. & Krachler, A. M. Against the tide: the role of bacterial adhesion in host colonization. Biochem. Soc. Trans. 44, 1571–1580 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Roberts, A. E., Kragh, K. N., Bjarnsholt, T. & Diggle, S. P. The limitations of in vitro experimentation in understanding biofilms and chronic infection. J. Mol. Biol. 427, 3646–3661 (2015).

    Article  CAS  PubMed  Google Scholar 

  56. Gristina, A. G. & Costerton, J. W. Bacterial adherence to biomaterials and tissue. The significance of its role in clinical sepsis. J. Bone Joint Surg. Am. 67A, 264–273 (1985).

    Article  Google Scholar 

  57. Costerton, J. W., Stewart, P. S. & Greenberg, E. P. Bacterial biofilms: a common cause of persistent infections. Science 284, 1318–1322 (1999).

    Article  CAS  PubMed  Google Scholar 

  58. Coenye, T. Response of sessile cells to stress: from changes in gene expression to phenotypic adaptation. FEMS Immunol. Med. Microbiol. 59, 239–225 (2010).

    Article  CAS  PubMed  Google Scholar 

  59. Sørensen, S. J., Bailey, M., Hansen, L. H., Kroer, N. & Wuertz, S. Studying plasmid horizontal transfer in situ: a critical review. Nat. Rev. Microbiol. 3, 700–710 (2005).

    Article  PubMed  CAS  Google Scholar 

  60. Monds, R. D. & O’Toole, G. A. The developmental model of microbial biofilms: ten years of a paradigm up for review. Trends Microbiol. 17, 73–87 (2009).

    Article  CAS  PubMed  Google Scholar 

  61. Moormeier, D. E. & Bayles, K. W. Staphylococcus aureus biofilm: a complex developmental organism. Mol. Microbiol. 104, 365–376 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Flemming, H. C. et al. Biofilms: an emergent form of bacterial life. Nat. Rev. Microbiol. 14, 563–575 (2016).

    Article  CAS  PubMed  Google Scholar 

  63. Arciola, C. R., Campoccia, D., Ravaioli, S. & Montanaro, L. Polysaccharide intercellular adhesin in biofilm: structural and regulatory aspects. Front. Cell. Infect. Microbiol. 5, 7 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Arciola, C. R. et al. Antibiotic resistance in exopolysaccharide-forming Staphylococcus epidermidis clinical isolates from orthopaedic implant infections. Biomaterials. 26, 6530–6535 (2005).

    Article  CAS  PubMed  Google Scholar 

  65. Vuong, C. et al. Staphylococcus epidermidis polysaccharide intercellular adhesin production significantly increases during tricarboxylic acid cycle stress. J. Bacteriol. 187, 2967–2973 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Knobloch, J. K. et al. Biofilm formation by Staphylococcus epidermidis depends on functional RsbU, an activator of the sigB operon: differential activation mechanisms due to ethanol and salt stress. J. Bacteriol. 183, 2624–2633 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Ferreira, A., Gray, M., Wiedmann, M. & Boor, K. J. Comparative genomic analysis of the sigB operon in Listeria monocytogenes and in other gram-positive bacteria. Curr. Microbiol. 48, 39–46 (2004).

    Article  CAS  PubMed  Google Scholar 

  68. Savage, V. J., Chopra, I. & O’Neill, A. J. Staphylococcus aureus biofilms promote horizontal transfer of antibiotic resistance. Antimicrob. Agents Chemother. 57, 1968–1970 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Obolski, U. & Hadany, L. Implications of stress-induced genetic variation for minimizing multidrug resistance in bacteria. BMC Med. 10, 89 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  70. Schaeffer, C. R. et al. Versatility of biofilm matrix molecules in Staphylococcus epidermidis: clinical isolates and importance of polysaccharide intercellular adhesin expression during high shear stress. mSphere 1, e00165–16 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Ziebuhr, W. et al. 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, 345–356 (1999).

    Article  CAS  PubMed  Google Scholar 

  72. Kozitskaya, S. et al. The bacterial insertion sequence element IS256 occurs preferentially in nosocomial Staphylococcus epidermidis isolates: association with biofilm formation and resistance to aminoglycosides. Infect. Immun. 72, 1210–1215 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Montanaro, L. et al. Extracellular DNA in biofilms. Int. J. Artif. Organs 34, 824–831 (2011).

    Article  CAS  PubMed  Google Scholar 

  74. Roberts, A. P. & Kreth, J. The impact of horizontal gene transfer on the adaptive ability of the human oral microbiome. Front. Cell. Infect. Microbiol. 4, 124 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  75. Thurlow, L. R. et al. Staphylococcus aureus biofilms prevent macrophage phagocytosis and attenuate inflammation in vivo. J. Immunol. 186, 6585–6596 (2011).

    Article  CAS  PubMed  Google Scholar 

  76. Vorkapic, D., Pressler, K. & Schild, S. Multifaceted roles of extracellular DNA in bacterial physiology. Curr. Genet. 62, 71–79 (2016).

    Article  CAS  PubMed  Google Scholar 

  77. Turnbull, L. et al. Explosive cell lysis as a mechanism for the biogenesis of bacterial membrane vesicles and biofilms. Nat. Commun. 7, 11220 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Zatorska, B. et al. Does extracellular DNA production vary in Staphylococcal biofilms isolated from infected implants versus controls? Clin. Orthop. Relat. Res. 475, 2105–2113 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  79. Thomas, V. C., Thurlow, L. R., Boyle, D. & Hancock, L. E. Regulation of autolysis-dependent extracellular DNA release by Enterococcus faecalis extracellular proteases influences biofilm development. J. Bacteriol. 90, 5690–5698 (2008).

    Article  CAS  Google Scholar 

  80. Thomas, V. C. & Hancock, L. E. Suicide and fratricide in bacterial biofilms. Int. J. Artif. Organs. 32, 537–544 (2009).

    Article  CAS  PubMed  Google Scholar 

  81. Xia, G., Kohler, T. & Peschel, A. The wall teichoic acid and lipoteichoic acid polymers of Staphylococcus aureus. Int. J. Med. Microbiol. 300, 148–154 (2010).

    Article  CAS  PubMed  Google Scholar 

  82. Fedtke, I. et al. A Staphylococcus aureus ypfP mutant with strongly reduced lipoteichoic acid (LTA) content: LTA governs bacterial surface properties and autolysin activity. Mol. Microbiol. 65, 1078–1091 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Fabretti, F. et al. Alanine esters of enterococcal lipoteichoic acid play a role in biofilm formation and resistance to antimicrobial peptides. Infect. Immun. 74, 4164–4171 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Sabaté Brescó, M. et al. Pathogenic mechanisms and host interactions in Staphylococcus epidermidis device-related infection. Front. Microbiol. 8, 1401 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  85. Patel, J. D., Colton, E., Ebert, M. & Anderson, J. M. Gene expression during S. epidermidis biofilm formation on biomaterials. J. Biomed. Mater. Res. A. 100, 2863–2869 (2012). This paper describes how the enhanced expression of the atlE, aap, agr and ica genes has an important role in initial foreign body colonization and, potentially, in the establishment of a device-associated infections.

    Article  PubMed  CAS  Google Scholar 

  86. Vandecasteele, S. J., Peetermans, W. E., Merckx, R. & Van Eldere, J. Expression of biofilm-associated genes in Staphylococcus epidermidis during in vitro and in vivo foreign body infections. J. Infect. Dis. 188, 730–737 (2003).

    Article  CAS  PubMed  Google Scholar 

  87. Le, K. Y. & Otto, M. Quorum-sensing regulation in staphylococci-an overview. Front. Microbiol. 6, 1174 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  88. Boles, B. R. & Horswill, A. R. Agr-mediated dispersal of Staphylococcus aureus biofilms. PLoS Pathog. 4, e1000052 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Yu, D., Zhao, L., Xue, T. & Sun, B. Staphylococcus aureus autoinducer-2 quorum sensing decreases biofilm formation in an icaR-dependent manner. BMC Microbiol. 12, 288 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Xue, T., Ni, J., Shang, F., Chen, X. & Zhang, M. Autoinducer-2 increases biofilm formation via an ica- and bhp-dependent manner in Staphylococcus epidermidis RP62A. Microbes Infect. 17, 345–352 (2015).

    Article  CAS  PubMed  Google Scholar 

  91. McDougald, D., Rice, S. A., Barraud, N., Steinberg, P. D. & Kjelleberg, S. Should we stay or should we go: mechanisms and ecological consequences for biofilm dispersal. Nat. Rev. Microbiol. 10, 39–50 (2011).

    Article  PubMed  CAS  Google Scholar 

  92. Solano, C., Echeverz, M. & Lasa, I. Biofilm dispersion and quorum sensing. Curr. Opin. Microbiol. 18, 96–104 (2014).

    Article  CAS  PubMed  Google Scholar 

  93. Peschel, A. & Otto, M. Phenol-soluble modulins and staphylococcal infection. Nat. Rev. Microbiol. 11, 667–673 (2013). This paper describes how PSMs cause lysis of red and white blood cells, stimulate inflammatory responses and contribute to biofilm development and the dissemination of biofilm-associated infections. Moreover, they kill human neutrophils after phagocytosis.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Lister, J. L. & Horswill, A. R. Staphylococcus aureus biofilms: recent developments in biofilm dispersal. Front. Cell. Infect. Microbiol. 4, 178 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  95. Le, K. Y., Dastgheyb, S., Ho, T. V. & Otto, M. Molecular determinants of staphylococcal biofilm dispersal and structuring. Front. Cell. Infect. Microbiol. 4, 167 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  96. Wang, R. et al. Staphylococcus epidermidis surfactant peptides promote biofilm maturation and dissemination of biofilm-associated infection in mice. J. Clin. Invest. 121, 238–248 (2011).

    Article  CAS  PubMed  Google Scholar 

  97. Karatan, E. & Watnick, P. Signals, regulatory networks, and materials that buildand break bacterial biofilms. Microbiol. Mol. Biol. Rev. 73, 310–347 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Patel, J. D., Krupka, T. & Anderson, J. M. iNOS-mediated generation of reactive oxygen and nitrogen species by biomaterial-adherent neutrophils. J. Biomed. Mater. Res. A. 80, 381–390 (2007).

    Article  PubMed  CAS  Google Scholar 

  99. Kaplan, S. S., Basford, R. E., Mora, E., Jeong, M. H. & Simmons, R. L. Biomaterial-induced alterations of neutrophil superoxide production. J. Biomed. Mater. Res. 26, 1039–1051 (1992).

    Article  CAS  PubMed  Google Scholar 

  100. Zimmerli, W., Waldvogel, F. A., Vaudaux, P. & Nydeggerm, U. E. Pathogenesis of foreign body infection: description and characteristics of an animal model. J. Infect. Dis. 146, 487–497 (1982).

    Article  CAS  PubMed  Google Scholar 

  101. Campoccia, D. et al. Orthopedic implant infections: incompetence of Staphylococcus epidermidis. Staphylococcus lugdunensis, and Enterococcus faecalis to invade osteoblasts. J. Biomed. Mater. Res. A 104, 788–801 (2016).

    Article  CAS  PubMed  Google Scholar 

  102. Josse, J., Velard, F. & Gangloff, S. C. Staphylococcus aureus versus osteoblast: relationship and consequences in osteomyelitis. Front. Cell. Infect. Microbiol. https://doi.org/10.3389/fcimb.2015.00085 (2015).

  103. Fowler, T. et al. Cellular invasion by Staphylococcus aureus involves a fibronectin bridge between the bacterial fibronectin-binding MSCRAMMs and host cell beta1 integrins. Eur. J. Cell Biol. 279, 672–679 (2000).

    Article  Google Scholar 

  104. Alexander, E. H. et al. Staphylococcus aureus-induced tumor necrosis factor – related apoptosis–inducing ligand expression mediates apoptosis and caspase-8 activation in infected osteoblasts. BMC Microbiol. 3, 5–16 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  105. Reilly, S. S., Hudson, M. C., Kellam, J. F. & Ramp, W. K. In vivo internalization of Staphylococcus aureus by embryonic chick osteoblasts. Bone 26, 63–70 (2000).

    Article  CAS  PubMed  Google Scholar 

  106. Maali, Y. et al. Pathophysiological mechanisms of Staphylococcus non-aureus bone and joint infection: interspecies homogeneity and specific behavior of S. pseudintermedius. Front. Microbiol. 7, 1063 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  107. Bui, L. M., Conlon, B. P. & Kidd, S. P. Antibiotic tolerance and the alternative lifestyles of Staphylococcus aureus. Essays Biochem. 61, 71–79 (2017).

    Article  PubMed  Google Scholar 

  108. Proctor, R. A. et al. Small colony variants: a pathogenic form of bacteria that facilitates persistent and recurrent infections. Nat. Rev. Microbiol. 4, 295–305 (2006).

    Article  CAS  PubMed  Google Scholar 

  109. Tuchscherr, L. et al. Staphylococcus aureus small-colony variants are adapted phenotypes for intracellular persistence. J. Infect. Dis. 202, 1031–1040 (2010).

    Article  PubMed  Google Scholar 

  110. Garzoni, C. & Kelley, W. L. Staphylococcus aureus: new evidence for intracellular persistence. Trends Microbiol. 17, 59–65 (2009).

    Article  CAS  PubMed  Google Scholar 

  111. Sendi, P. et al. Staphylococcus aureus small colony variants in prosthetic joint infection. Clin. Infect. Dis. 43, 961–967 (2006).

    Article  PubMed  Google Scholar 

  112. Hamza, T. et al. Intra-cellular Staphylococcus aureus alone causes infection in vivo. Eur. Cell. Mater. 25, 341–350 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. de Mesy Bentley, K. L. et al. Evidence of Staphylococcus aureus deformation, proliferation, and migration in canaliculi of live cortical bone in murine models of osteomyelitis. J. Bone Miner. Res. 32, 985–990 (2017).

    Article  PubMed  CAS  Google Scholar 

  114. Crémet, L. et al. Innate immune evasion of Escherichia coli clinical strains from orthopedic implant infections. Eur. J. Clin. Microbiol. Infect. Dis. 35, 993–999 (2016).

    Article  PubMed  CAS  Google Scholar 

  115. McGuinness, W. A., Kobayashi, S. D. & DeLeo, F. R. Evasion of neutrophil Killing by Staphylococcus aureus. Pathogens 5, E32 (2016).

    Article  PubMed  CAS  Google Scholar 

  116. Thammavongsa, V., Kim, H. K., Missiakas, D. & Schneewind, O. Staphylococcal manipulation of host immune responses. Nat. Rev. Microbiol. 13, 529–543 (2015). This is a very comprehensive review illustrating the many mechanisms that S. aureus uses to elude the host immune response.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Scherr, T. D. et al. Staphylococcus aureus biofilms induce macrophage dysfunction through leukocidin AB and alpha-toxin. mBio. 6, e01021–15 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Foster, T. J. Immune evasion by staphylococci. Nat. Rev. Microbiol. 3, 948–958 (2005).

    Article  CAS  PubMed  Google Scholar 

  119. Cheung, G. Y. et al. Staphylococcus epidermidis strategies to avoid killing by human neutrophils. PLoS Pathog. 6, e1001133 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  120. Donaldson, K., Murphy, F. A., Duffin, R. & Poland Asbestos, C. A. carbon nanotubes and the pleural mesothelium: a review of the hypothesis regarding the role of long fibre retention in the parietal pleura, inflammation and mesothelioma. Part. Fibre Toxicol. 7, 5 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  121. Leid, J. G., Shirtliff, M. E., Costerton, J. W. & Stoodley, P. Human leukocytes adhere to, penetrate, and respond to Staphylococcus aureus biofilms. Infect. Immun. 70, 6339–6345 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Hanke, M. L., Angle, A. & Kielian, T. MyD88-dependent signaling influences fibrosis and alternative macrophage activation during Staphylococcus aureus biofilm infection. PLoS One. 7, e42476 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Hanke, M. L. & Kielian, T. Deciphering mechanisms of staphylococcal biofilm evasion of host immunity. Front. Cell. Infect. Microbiol. 2, 62 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  124. Gries, C. M. & Kielian, T. Staphylococcal biofilms and immune polarization during prosthetic joint infection. J. Am. Acad. Orthop. Surg. 25, S20–S24 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  125. Benoit, M., Desnues, B. & Mege, J. L. Macrophage polarization in bacterial infections. J. Immunol. 181, 3733–3739 (2008).

    Article  CAS  PubMed  Google Scholar 

  126. Mbalaviele, G., Novack, D. V., Schett, G. & Teitelbaum, S. L. Inflammatory osteolysis: a conspiracy against bone. J. Clin. Invest. 127, 2030–2039 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  127. Heim, C. E. et al. IL-12 promotes myeloid-derived suppressor cell recruitment and bacterial persistence during Staphylococcus aureus orthopedic implant infection. J. Immunol. 194, 3861–3872 (2015).

    Article  CAS  PubMed  Google Scholar 

  128. Fernández-Sampedro, M. et al. Accuracy of different diagnostic tests for early, delayed and late prosthetic joint infection. BMC Infect. Dis. 17, 592 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  129. Costerton, J. W. et al. New methods for the detection of orthopedic and other biofilm infections. FEMS Immunol. Med. Microbiol. 61, 133–140 (2011).

    Article  CAS  PubMed  Google Scholar 

  130. Arciola, C. R., Montanaro, L. & Costerton, J. W. New trends in diagnosis and control strategies for implant infections. Int. J. Artif. Organs. 34, 727–736 (2011).

    Article  CAS  PubMed  Google Scholar 

  131. Harris, L. G. et al. Rapid identification of staphylococci from prosthetic joint infections using MALDI-TOF mass-spectrometry. Int. J. Artif. Organs. 33, 568–574 (2010).

    Article  CAS  PubMed  Google Scholar 

  132. Deurenberg, R. H. et al. Application of next generation sequencing in clinical microbiology and infection prevention. J. Biotechnol. 243, 16–24 (2017).

    Article  CAS  PubMed  Google Scholar 

  133. Mühlhofer, H. M. et al. Prosthetic joint infection development of an evidence-based diagnostic algorithm. Eur. J. Med. Res. 22, 8 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  134. Tagini, F. & Greub, G. Bacterial genome sequencing in clinical microbiology: a pathogen-oriented review. Eur. J. Clin. Microbiol. Infect. Dis. 36, 2007–2020 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. van Belkum, A., Welker, M., Pincus, D., Charrier, J. P. & Girard, V. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry in clinical microbiology: what are the current issues? Ann. Lab Med. 7, 475–483 (2017).

    Article  CAS  Google Scholar 

  136. Deirmengian, C. et al. The alpha-defensin test for periprosthetic joint infection responds to a wide spectrum of organisms. Clin. Orthop. Relat. Res. 473, 2229–2235 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  137. Aggarwal, V. K. et al. Mitigation and education. J. Orthop. Res. 32, S16–25 (2014).

    Article  PubMed  Google Scholar 

  138. Greenky, M., Gandhi, K., Pulido, L., Restrepo, C. & Parvizi, J. Preoperative anemia in total joint arthroplasty: is it associated with periprosthetic joint infection? Clin. Orthop. Relat. Res. 470, 2695–2701 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  139. Ma, N. et al. Systematic review of a patient care bundle in reducing staphylococcal infections in cardiac and orthopaedic surgery. ANZ J. Surg. 87, 239–246 (2017).

    Article  PubMed  Google Scholar 

  140. Bode, L. G. et al. Preventing surgical-site infections in nasal carriers of Staphylococcus aureus. N. Engl. J. Med. 362, 9–17 (2010).

    Article  CAS  PubMed  Google Scholar 

  141. Gurusamy, K. S., Koti, R., Wilson, P. & Davidson, B. R. Antibiotic prophylaxis for the prevention of methicillin-resistant Staphylococcus aureus (MRSA) related complications in surgical patients. Cochrane Database Syst. Rev. 8, CD010268 (2013).

    Google Scholar 

  142. Voigt, J., Mosier, M. & Darouiche, R. Antibiotics and antiseptics for preventing infection in people receiving revision total hip and knee prostheses: a systematic review of randomized controlled trials. BMC Infect. Dis. 16, 749 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  143. Campoccia, D., Montanaro, L. & Arciola, C. R. A review of the biomaterials technologies for infection-resistant surfaces. Biomaterials 34, 8533–8554 (2013). This paper describes innovative technologies that are used to develop new biomaterials and surfaces endowed with anti-infective properties, based on antifouling, bactericidal and anti-biofilm activities.

    Article  CAS  PubMed  Google Scholar 

  144. Alt, V. Antimicrobial coated implants in trauma and orthopaedics-a clinical review and risk-benefit analysis. Injury 48, 599–607 (2017).

    Article  PubMed  Google Scholar 

  145. Maddikeri, R. R. et al. Reduced medical infection related bacterial strains adhesion on bioactive RGD modified titanium surfaces: a first step toward cell selective surfaces. J. Biomed. Mater. Res. A. 84, 425–435 (2008).

    Article  CAS  PubMed  Google Scholar 

  146. Raphel, J., Holodniy, M., Goodman, S. B. & Heilshorn, S. C. Multifunctional coatings to simultaneously promote osseointegration and prevent infection of orthopaedic implants. Biomaterials 84, 301–314 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Chung, K. K. et al. Impact of engineered surface microtopography on biofilm formation of Staphylococcus aureus. Biointerphases 2, 89–94 (2007).

    Article  CAS  PubMed  Google Scholar 

  148. Jaggessar, A., Shahali, H., Mathew, A. & Yarlagadda, P. K. D. V. Bio-mimicking nano and micro-structured surface fabrication for antibacterial properties in medical implants. J. Nanobiotechnology 15, 64 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  149. Leite, P. S., Figueiredo, S. & Sousa, R. Prosthetic joint infection: report on the one versus two-stage exchange EBJIS survey. J. Bone Joint Infect. 1, 1–6 (2016).

    Article  Google Scholar 

  150. Coiffier, G., Albert, J. D., Arvieux, C. & Guggenbuhl, P. Optimizing combination rifampin therapy for staphylococcal osteoarticular infections. Joint Bone Spine. 80, 11–17 (2013).

    Article  CAS  PubMed  Google Scholar 

  151. Achermann, Y. et al. Factors associated with rifampin resistance in staphylococcal periprosthetic joint infections (PJI): a matched case-control study. Infection 41, 431–437 (2013).

    Article  CAS  PubMed  Google Scholar 

  152. König, D. P., Schierholz, J. M., Münnich, U. & Rütt, J. Treatment of staphylococcal implant infection with rifampicin-ciprofloxacin in stable implants. Arch. Orthop. Trauma Surg. 121, 297–299 (2001).

    Article  PubMed  Google Scholar 

  153. Hancock, R. E., Haney, E. F. & Gill, E. E. The immunology of host defence peptides: beyond antimicrobial activity. Nat. Rev. Immunol. 16, 321–234 (2016).

    Article  CAS  PubMed  Google Scholar 

  154. Pendleton, J. N., Gorman, S. P. & Gilmore, B. F. Clinical relevance of the ESKAPE pathogens. Expert. Rev. Anti Infect. Ther. 11, 297–308 (2013).

    Article  CAS  PubMed  Google Scholar 

  155. Bionda, N. et al. Identification of novel cyclic lipopeptides from a positional scanning combinatorial library with enhanced antibacterial and antibiofilm activities. Eur. J. Med. Chem. 108, 354–363 (2016).

    Article  CAS  PubMed  Google Scholar 

  156. Malcher, J., Wesoły, J. & Bluyssen, H. A. Molecular properties and medical applications of peptide nucleic acids. Mini Rev. Med. Chem. 14, 401–410 (2014).

    Article  CAS  PubMed  Google Scholar 

  157. Hansen, A. M. et al. Antibacterial peptide nucleic acid-antimicrobial peptide (PNA-AMP) conjugates: antisense targeting of fatty acid biosynthesis. Bioconjug. Chem. 27, 863–867 (2016).

    Article  CAS  PubMed  Google Scholar 

  158. Bai, H. et al. Antisense inhibition of gene expression and growth in gram-negative bacteria by cell-penetrating peptide conjugates of peptide nucleic acids targeted to rpoD gene. Biomaterials 33, 659–667 (2012).

    Article  CAS  PubMed  Google Scholar 

  159. Küçükdurmaz, F. & Parvizi, J. The prevention of periprosthetic joint infections. Open Orthop. J. 10, 589–599 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  160. Brauner, A., Fridman, O., Gefen, O. & Balaban, N. Q. Distinguishing between resistance, tolerance and persistence to antibiotic treatment. Nat. Rev. Microbiol. 14, 320–330 (2016). This is an opinion article that clarifies and defines the different concepts of resistance, tolerance and persistence to antibiotics.

    Article  CAS  PubMed  Google Scholar 

  161. Wang, X. et al. Increased intracellular activity of MP1102 and NZ2114 against Staphylococcus aureus in vitro and in vivo. Sci. Rep. 8, 4204 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  162. Feldman, M. D., Petersen, A. J., Karliner, L. S. & Tice, J. A. Who is responsible for evaluating the safety and effectiveness of medical devices? The role of independent technology assessment. J. Gen. Intern. Med. 23, 57–63 (2008).

    Article  PubMed  Google Scholar 

  163. McIntyre, W. F. & Healey, J. S. Cardiac implantable electronic device infections: from recognizing risk to prevention. Heart Rhythm. 14, 846–847 (2017).

    Article  PubMed  Google Scholar 

  164. Andersen, O. Z. et al. Accelerated bone ingrowth by local delivery of strontium from surface functionalized titanium implants. Biomaterials 34, 5883–5890 (2013).

    Article  CAS  PubMed  Google Scholar 

  165. Eaves, F. 3rd & Nahai, F. Anaplastic large cell lymphoma and breast implants: FDA report. Aesthet. Surg. J. 31, 467–468 (2011).

    Article  PubMed  Google Scholar 

  166. Rello, J. et al. VAP outcomes scientific advisory group. Epidemiology and outcomes of ventilator-associated pneumonia in a large US database. Chest 122, 2115–2121 (2002).

    Article  PubMed  Google Scholar 

  167. del Pozo, J. L. & Patel, R. The challenge of treating biofilm-associated bacterial infections. Clin. Pharmacol. Ther. 82, 204–209 (2007).

    Article  PubMed  CAS  Google Scholar 

  168. Michiels, J. E., Van den Bergh, B., Verstraeten, N. & Michiels, J. Molecular mechanisms and clinical implications of bacterial persistence. Drug Resist. Updat. 29, 76–89 (2016).

    Article  PubMed  Google Scholar 

  169. Lewis, K. Persister cells. Annu. Rev. Microbiol. 64, 357–372 (2010). This paper describes persister cells, which are dormant variants that form in microbial populations and are highly tolerant to antibiotics. Stress responses may act as general activators of persister formation.

    Article  CAS  PubMed  Google Scholar 

  170. Fisher, R. A., Gollan, B. & Helaine, S. Persistent bacterial infections and persister cells. Nat. Rev. Microbiol. 15, 453–464 (2017). This paper describes how bacterial persister cells avoid antibiotic-induced death by entering a physiologically dormant state, which makes them a major cause of antibiotic treatment failure and relapsing infections.

    Article  CAS  PubMed  Google Scholar 

  171. Allison, K. R., Brynildsen, M. P. & Collins, J. J. Metabolite-enabled eradication of bacterial persisters by aminoglycosides. Nature 473, 216–220 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Mina, E. G. & Marques, C. N. Interaction of Staphylococcus aureus persister cells with the host when in a persister state and following awakening. Sci. Rep. 6, 31342 (2016). This paper describes that, upon awakening, persister cells regain their ability to infect hosts.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Daghighi, S. et al. Persistence of a bioluminescent Staphylococcus aureus strain on and around degradable and non-degradable surgical meshes in amurine model. Acta Biomater. 8, 3991–3996 (2012).

    Article  CAS  PubMed  Google Scholar 

  174. Ravindran, S. & George, A. Multifunctional ECM proteins in bone and teeth. Exp. Cell. Res. 325, 148–154 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Ekdahl, K. N. et al. Dangerous liaisons: complement, coagulation, and kallikrein/kinin cross-talk act as a linchpin in the events leading to thromboinflammation. Immunol. Rev. 274, 245–269 (2016).

    Article  CAS  PubMed  Google Scholar 

  176. Janatova, J. Activation and control of complement, inflammation, and infection associated with the use of biomedical polymers. ASAIO J. 46, S53–62 (2000).

    Article  CAS  PubMed  Google Scholar 

  177. Vroman, L., Adams, A. L., Fischer, G. C. & Munoz, P. C. Interaction of high molecular weight kininogen, factor XII, and fibrinogen in plasma at interfaces. Blood 55, 156–159 (1980).

    Article  CAS  PubMed  Google Scholar 

  178. Selders, G. S. et al. An overview of the role of neutrophils in innate immunity, inflammation and host-biomaterial integration. Regen. Biomater. 4, 55–68 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Brinkmann, V. et al. Neutrophil extracellular traps kill bacteria. Science 303, 1532–1535 (2004).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors gratefully acknowledge M. P. Landini for the inspiring atmosphere at the Rizzoli Orthopaedic Institute. This work was supported by the POR-FESR 2014–2020 grant (Project No. 725827) and by the “5 per mille” grants to the Rizzoli Orthopaedic Institute.

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Glossary

Health-care-associated infections

An infection contracted by a patient while receiving medical care in a hospital or in another health-care facility (synonymous with nosocomial and hospital infection).

Opportunistic pathogens

Microorganisms that generally live harmlessly as commensals but can cause infection in hosts with lowered resistance to disease.

Granulation tissue

New connective tissue and capillaries that replace the fibrin matrix during wound healing.

Coagulase-negative staphylococci

(CNS). A broad group of staphylococci devoid of coagulase activity that includes some of the staphylococcal species that often cause hospital-acquired infections.

Total arthroplasty

A reconstructive surgical procedure consisting of replacement of a joint with an artificial prosthesis.

Wettability

Ability of a solid surface to reduce the surface tension of a liquid in contact with it so that the liquid spreads over the surface and wets it.

Extended Derjaguin–Landau–Verwey–Overbeek theory

(XDLVO theory). A theory that describes the interactions between material surfaces immersed in a liquid, taking into account the different attractive and repulsive forces (Lifshitz–van der Waals, electrical double layer and Lewis acid–base forces). It can be used to predict the interactions of bacteria and biomaterial surfaces.

Conjugation

A mechanism by which genetic material can transfer between bacterial cells. It involves direct cell-to-cell contact or a bridge-like connection between cells.

Quorum sensing system

A bacterial regulatory system based on signalling molecules (autoinducers) that reflect bacterial cell-population density and regulate gene expression in response to it.

Surfactant molecules

Compounds that lower the surface tension between two liquids or between a liquid and a solid.

Non-professional phagocytes

A variety of non-immune cells that are capable of phagocytosis, including fibroblasts, osteoblasts, keratinocytes and endothelial cells.

Professional phagocytes

A group of cells that includes phagocytes of the innate immune system, such as neutrophils, monocytes, macrophages, mast cells and dendritic cells.

Small colony variant

Slow-growing variant of bacteria that arises spontaneously and forms small colonies when grown in the laboratory. These variants are implicated in persistent infections.

Canaliculi

Thin, hair-like channels in the bone that link the lacunae with one another and with the Haversian canal.

Lacunae

Small cavities within the bone matrix in which single osteocytes are lodged.

ESKAPE pathogens

Acronym for a group of pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species) that are some of the main species that cause antimicrobial-resistant infections.

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Arciola, C.R., Campoccia, D. & Montanaro, L. Implant infections: adhesion, biofilm formation and immune evasion. Nat Rev Microbiol 16, 397–409 (2018). https://doi.org/10.1038/s41579-018-0019-y

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