Skip to main content
Top
Published in: Current Reviews in Musculoskeletal Medicine 3/2018

01-09-2018 | Prosthetic Joint Infection (S Nodzo and N Frisch, section editors)

Staphylococcus aureus Evasion of Host Immunity in the Setting of Prosthetic Joint Infection: Biofilm and Beyond

Authors: Benjamin F. Ricciardi, Gowrishankar Muthukrishnan, Elysia Masters, Mark Ninomiya, Charles C. Lee, Edward M. Schwarz

Published in: Current Reviews in Musculoskeletal Medicine | Issue 3/2018

Login to get access

Abstract

Purpose of Review

The incidence of complications from prosthetic joint infection (PJI) is increasing, and treatment failure remains high. We review the current literature with a focus on Staphylococcus aureus pathogenesis and biofilm, as well as treatment challenges, and novel therapeutic strategies.

Recent Findings

S. aureus biofilm creates a favorable environment that increases antibiotic resistance, impairs host immunity, and increases tolerance to nutritional deprivation. Secreted proteins from bacterial cells within the biofilm and the quorum-sensing agr system contribute to immune evasion. Additional immunoevasive properties of S. aureus include the formation of staphylococcal abscess communities (SACs) and canalicular invasion. Novel approaches to target biofilm and increase resistance to implant colonization include novel antibiotic therapy, immunotherapy, and local implant treatments.

Summary

Challenges remain given the diverse mechanisms developed by S. aureus to alter the host immune responses. Further understanding of these processes should provide novel therapeutic mechanisms to enhance eradication after PJI.
Literature
2.
go back to reference Lora-Tamayo J, Murillo O, Iribarren JA, Soriano A, Sánchez-Somolinos M, Baraia-Etxaburu JM, et al. A large multicenter study of methicillin-susceptible and methicillin-resistant Staphylococcus aureus prosthetic joint infections managed with implant retention. Clin Infect Dis. 2013;56(2):182–94. https://doi.org/10.1093/cid/cis746. PubMedCrossRef Lora-Tamayo J, Murillo O, Iribarren JA, Soriano A, Sánchez-Somolinos M, Baraia-Etxaburu JM, et al. A large multicenter study of methicillin-susceptible and methicillin-resistant Staphylococcus aureus prosthetic joint infections managed with implant retention. Clin Infect Dis. 2013;56(2):182–94. https://​doi.​org/​10.​1093/​cid/​cis746.​ PubMedCrossRef
6.
go back to reference Hall-Stoodley L, Costerton JW, Stoodley P. Bacterial biofilms: from the natural environment to infectious diseases. Nat Rev Microbiol. 2004;2(2):95–108.PubMedCrossRef Hall-Stoodley L, Costerton JW, Stoodley P. Bacterial biofilms: from the natural environment to infectious diseases. Nat Rev Microbiol. 2004;2(2):95–108.PubMedCrossRef
8.
go back to reference de Beer D, Stoodley P, Roe F, Lewandowski Z. Effects of biofilm structures on oxygen distribution and mass transport. Biotechnol Bioeng. 1994;43(11):1131–8.PubMedCrossRef de Beer D, Stoodley P, Roe F, Lewandowski Z. Effects of biofilm structures on oxygen distribution and mass transport. Biotechnol Bioeng. 1994;43(11):1131–8.PubMedCrossRef
10.
go back to reference Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science. 1999;284(5418):1318–22.PubMedCrossRef Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science. 1999;284(5418):1318–22.PubMedCrossRef
11.
go back to reference Mah TF, O'Toole GA. Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol. 2001;9(1):34–9.PubMedCrossRef Mah TF, O'Toole GA. Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol. 2001;9(1):34–9.PubMedCrossRef
12.
go back to reference Gristina AG, Hobgood CD, Webb LX, Myrvik QN. Adhesive colonization of biomaterials and antibiotic resistance. Biomaterials. 1987;8(6):423–6.PubMedCrossRef Gristina AG, Hobgood CD, Webb LX, Myrvik QN. Adhesive colonization of biomaterials and antibiotic resistance. Biomaterials. 1987;8(6):423–6.PubMedCrossRef
13.
go back to reference Jefferson KK, Goldmann DA, Pier GB. Use of confocal microscopy to analyze the rate of vancomycin penetration through Staphylococcus aureus biofilms. Antimicrob Agents Chemother. 2005;49(6):2467–73.PubMedPubMedCentralCrossRef Jefferson KK, Goldmann DA, Pier GB. Use of confocal microscopy to analyze the rate of vancomycin penetration through Staphylococcus aureus biofilms. Antimicrob Agents Chemother. 2005;49(6):2467–73.PubMedPubMedCentralCrossRef
15.
go back to reference Anderl JN, Franklin MJ, Stewart PS. Role of antibiotic penetration limitation in Klebsiella pneumoniae biofilm resistance to ampicillin and ciprofloxacin. Antimicrob Agents Chemother. 2000;44(7):1818–24.PubMedPubMedCentralCrossRef Anderl JN, Franklin MJ, Stewart PS. Role of antibiotic penetration limitation in Klebsiella pneumoniae biofilm resistance to ampicillin and ciprofloxacin. Antimicrob Agents Chemother. 2000;44(7):1818–24.PubMedPubMedCentralCrossRef
16.
go back to reference Roberts ME, Stewart PS. Modelling protection from antimicrobial agents in biofilms through the formation of persister cells. Microbiology. 2005;151(Pt 1):75–80.PubMedCrossRef Roberts ME, Stewart PS. Modelling protection from antimicrobial agents in biofilms through the formation of persister cells. Microbiology. 2005;151(Pt 1):75–80.PubMedCrossRef
18.
go back to reference Kahl B, Herrmann M, Everding AS, Koch HG, Becker K, Harms E, et al. Persistent infection with small colony variant strains of Staphylococcus aureus in patients with cystic fibrosis. J Infect Dis. 1998;177(4):1023–9.PubMedCrossRef Kahl B, Herrmann M, Everding AS, Koch HG, Becker K, Harms E, et al. Persistent infection with small colony variant strains of Staphylococcus aureus in patients with cystic fibrosis. J Infect Dis. 1998;177(4):1023–9.PubMedCrossRef
19.
go back to reference Sendi P, Rohrbach M, Graber P, Frei R, Ochsner PE, Zimmerli W. Staphylococcus aureus small colony variants in prosthetic joint infection. Clin Infect Dis. 2006;43(8):961–7.PubMedCrossRef Sendi P, Rohrbach M, Graber P, Frei R, Ochsner PE, Zimmerli W. Staphylococcus aureus small colony variants in prosthetic joint infection. Clin Infect Dis. 2006;43(8):961–7.PubMedCrossRef
21.
go back to reference Whiteley M, Bangera MG, Bumgarner RE, Parsek MR, Teitzel GM, Lory S, et al. Gene expression in Pseudomonas aeruginosa biofilms. Nature. 2001;413(6858):860–4.PubMedCrossRef Whiteley M, Bangera MG, Bumgarner RE, Parsek MR, Teitzel GM, Lory S, et al. Gene expression in Pseudomonas aeruginosa biofilms. Nature. 2001;413(6858):860–4.PubMedCrossRef
22.
go back to reference Werner E, Roe F, Bugnicourt A, Franklin MJ, Heydorn A, Molin S, et al. Stratified growth in Pseudomonas aeruginosa biofilms. Appl Environ Microbiol. 2004;70(10):6188–96.PubMedPubMedCentralCrossRef Werner E, Roe F, Bugnicourt A, Franklin MJ, Heydorn A, Molin S, et al. Stratified growth in Pseudomonas aeruginosa biofilms. Appl Environ Microbiol. 2004;70(10):6188–96.PubMedPubMedCentralCrossRef
24.
go back to reference Donlan RM, Piede JA, Heyes CD, Sanii L, Murga R, Edmonds P, et al. Model system for growing and quantifying Streptococcus pneumoniae biofilms in situ and in real time. Appl Environ Microbiol. 2004;70(8):4980–8.PubMedPubMedCentralCrossRef Donlan RM, Piede JA, Heyes CD, Sanii L, Murga R, Edmonds P, et al. Model system for growing and quantifying Streptococcus pneumoniae biofilms in situ and in real time. Appl Environ Microbiol. 2004;70(8):4980–8.PubMedPubMedCentralCrossRef
25.
go back to reference Ceri H, Olson ME, Stremick C, Read RR, Morck D, Buret A. The Calgary Biofilm Device: new technology for rapid determination of antibiotic susceptibilities of bacterial biofilms. J Clin Microbiol. 1999;37(6):1771–6.PubMedPubMedCentral Ceri H, Olson ME, Stremick C, Read RR, Morck D, Buret A. The Calgary Biofilm Device: new technology for rapid determination of antibiotic susceptibilities of bacterial biofilms. J Clin Microbiol. 1999;37(6):1771–6.PubMedPubMedCentral
26.
go back to reference Yang L, Haagensen JA, Jelsbak L, Johansen HK, Sternberg C, Høiby N, et al. In situ growth rates and biofilm development of Pseudomonas aeruginosa populations in chronic lung infections. J Bacteriol. 2008;190(8):2767–76.PubMedCrossRef Yang L, Haagensen JA, Jelsbak L, Johansen HK, Sternberg C, Høiby N, et al. In situ growth rates and biofilm development of Pseudomonas aeruginosa populations in chronic lung infections. J Bacteriol. 2008;190(8):2767–76.PubMedCrossRef
27.
go back to reference • Nishitani K, Sutipornpalangkul W, de Mesy Bentley KL, Varrone JJ, Bello-Irizarry SN, Ito H, et al. Quantifying the natural history of biofilm formation in vivo during the establishment of chronic implant-associated Staphylococcus aureus osteomyelitis in mice to identify critical pathogen and host factors. J Orthop Res. 2015;33(9):1311–9. https://doi.org/10.1002/jor.22907. The natural history of in vivo biofilm formation with multiple Staphylococcus aureus strains were examined in a clinically relevant murine model with an implant-associated infection. PubMedPubMedCentralCrossRef • Nishitani K, Sutipornpalangkul W, de Mesy Bentley KL, Varrone JJ, Bello-Irizarry SN, Ito H, et al. Quantifying the natural history of biofilm formation in vivo during the establishment of chronic implant-associated Staphylococcus aureus osteomyelitis in mice to identify critical pathogen and host factors. J Orthop Res. 2015;33(9):1311–9. https://​doi.​org/​10.​1002/​jor.​22907. The natural history of in vivo biofilm formation with multiple Staphylococcus aureus strains were examined in a clinically relevant murine model with an implant-associated infection. PubMedPubMedCentralCrossRef
28.
go back to reference Ulphani JS, Rupp ME. Model of Staphylococcus aureus central venous catheter-associated infection in rats. Lab Anim Sci. 1999;49(3):283–7.PubMed Ulphani JS, Rupp ME. Model of Staphylococcus aureus central venous catheter-associated infection in rats. Lab Anim Sci. 1999;49(3):283–7.PubMed
29.
go back to reference Cirioni O, Giacometti A, Ghiselli R, Bergnach C, Orlando F, Mocchegiani F, et al. Pre-treatment of central venous catheters with the cathelicidin BMAP-28 enhances the efficacy of antistaphylococcal agents in the treatment of experimental catheter-related infection. Peptides. 2006;27(9):2104–10.PubMedCrossRef Cirioni O, Giacometti A, Ghiselli R, Bergnach C, Orlando F, Mocchegiani F, et al. Pre-treatment of central venous catheters with the cathelicidin BMAP-28 enhances the efficacy of antistaphylococcal agents in the treatment of experimental catheter-related infection. Peptides. 2006;27(9):2104–10.PubMedCrossRef
31.
go back to reference Foster TJ. The remarkably multifunctional fibronectin binding proteins of Staphylococcus aureus. Eur J Clin Microbiol Infect Dis. 2016;35(12):1923–31.PubMedCrossRef Foster TJ. The remarkably multifunctional fibronectin binding proteins of Staphylococcus aureus. Eur J Clin Microbiol Infect Dis. 2016;35(12):1923–31.PubMedCrossRef
32.
go back to reference Patti JM, Allen BL, McGavin MJ, Höök M. MSCRAMM-mediated adherence of microorganisms to host tissues. Annu Rev Microbiol. 1994;48:585–617.PubMedCrossRef Patti JM, Allen BL, McGavin MJ, Höök M. MSCRAMM-mediated adherence of microorganisms to host tissues. Annu Rev Microbiol. 1994;48:585–617.PubMedCrossRef
34.
go back to reference Ní Eidhin D, Perkins S, Francois P, Vaudaux P, Höök M, Foster TJ. Clumping factor B (ClfB), a new surface-located fibrinogen-binding adhesin of Staphylococcus aureus. Mol Microbiol. 1998;30(2):245–57.PubMedCrossRef Ní Eidhin D, Perkins S, Francois P, Vaudaux P, Höök M, Foster TJ. Clumping factor B (ClfB), a new surface-located fibrinogen-binding adhesin of Staphylococcus aureus. Mol Microbiol. 1998;30(2):245–57.PubMedCrossRef
39.
go back to reference •• Wang Y, Cheng LI, Helfer DR, Ashbaugh AG, Miller RJ, Tzomides AJ, et al. Mouse model of hematogenous implant-related Staphylococcus aureus biofilm infection reveals therapeutic targets. Proc Natl Acad Sci U S A. 2017;114(26):E5094–102. https://doi.org/10.1073/pnas.1703427114. The authors developed a murine hematogenous implant-related infection model and demonstrated that a combination of neutralizing human monoclonal antibodies against α-toxin and ClfA inhibited in vitro biofilm formation, propensity for infection in vivo, and reduced bacterial burden in vivo. PubMedPubMedCentralCrossRef •• Wang Y, Cheng LI, Helfer DR, Ashbaugh AG, Miller RJ, Tzomides AJ, et al. Mouse model of hematogenous implant-related Staphylococcus aureus biofilm infection reveals therapeutic targets. Proc Natl Acad Sci U S A. 2017;114(26):E5094–102. https://​doi.​org/​10.​1073/​pnas.​1703427114. The authors developed a murine hematogenous implant-related infection model and demonstrated that a combination of neutralizing human monoclonal antibodies against α-toxin and ClfA inhibited in vitro biofilm formation, propensity for infection in vivo, and reduced bacterial burden in vivo. PubMedPubMedCentralCrossRef
41.
go back to reference Clarke SR, Mohamed R, Bian L, Routh AF, Kokai-Kun JF, Mond JJ, et al. The Staphylococcus aureus surface protein IsdA mediates resistance to innate defenses of human skin. Cell Host Microbe. 2007;1(3):199–212.PubMedCrossRef Clarke SR, Mohamed R, Bian L, Routh AF, Kokai-Kun JF, Mond JJ, et al. The Staphylococcus aureus surface protein IsdA mediates resistance to innate defenses of human skin. Cell Host Microbe. 2007;1(3):199–212.PubMedCrossRef
44.
go back to reference Shopsin B, Gomez M, Montgomery SO, Smith DH, Waddington M, Dodge DE, et al. Evaluation of protein A gene polymorphic region DNA sequencing for typing of Staphylococcus aureus strains. J Clin Microbiol. 1999;37(11):3556–63.PubMedPubMedCentral Shopsin B, Gomez M, Montgomery SO, Smith DH, Waddington M, Dodge DE, et al. Evaluation of protein A gene polymorphic region DNA sequencing for typing of Staphylococcus aureus strains. J Clin Microbiol. 1999;37(11):3556–63.PubMedPubMedCentral
47.
go back to reference Gómez MI, Lee A, Reddy B, Muir A, Soong G, Pitt A, et al. Staphylococcus aureus protein A induces airway epithelial inflammatory responses by activating TNFR1. Nat Med. 2004;10(8):842–8.PubMedCrossRef Gómez MI, Lee A, Reddy B, Muir A, Soong G, Pitt A, et al. Staphylococcus aureus protein A induces airway epithelial inflammatory responses by activating TNFR1. Nat Med. 2004;10(8):842–8.PubMedCrossRef
48.
go back to reference Silverman GJ, Cary S, Graille M, Curtiss VE, Wagenknecht R, Luo L, et al. A B-cell superantigen that targets B-1 lymphocytes. Curr Top Microbiol Immunol. 2000;252:251–63.PubMed Silverman GJ, Cary S, Graille M, Curtiss VE, Wagenknecht R, Luo L, et al. A B-cell superantigen that targets B-1 lymphocytes. Curr Top Microbiol Immunol. 2000;252:251–63.PubMed
49.
go back to reference Graille M, Stura EA, Corper AL, Sutton BJ, Taussig MJ, Charbonnier JB, et al. Crystal structure of a Staphylococcus aureus protein A domain complexed with the Fab fragment of a human IgM antibody: structural basis for recognition of B-cell receptors and superantigen activity. Proc Natl Acad Sci U S A. 2000;97(10):5399–404.PubMedPubMedCentralCrossRef Graille M, Stura EA, Corper AL, Sutton BJ, Taussig MJ, Charbonnier JB, et al. Crystal structure of a Staphylococcus aureus protein A domain complexed with the Fab fragment of a human IgM antibody: structural basis for recognition of B-cell receptors and superantigen activity. Proc Natl Acad Sci U S A. 2000;97(10):5399–404.PubMedPubMedCentralCrossRef
55.
57.
go back to reference Brady RA, Leid JG, Camper AK, Costerton JW, Shirtliff ME. Identification of Staphylococcus aureus proteins recognized by the antibody-mediated immune response to a biofilm infection. Infect Immun. 2006;74(6):3415–26.PubMedPubMedCentralCrossRef Brady RA, Leid JG, Camper AK, Costerton JW, Shirtliff ME. Identification of Staphylococcus aureus proteins recognized by the antibody-mediated immune response to a biofilm infection. Infect Immun. 2006;74(6):3415–26.PubMedPubMedCentralCrossRef
59.
go back to reference Biswas R, Voggu L, Simon UK, Hentschel P, Thumm G, Götz F. Activity of the major staphylococcal autolysin Atl. FEMS Microbiol Lett. 2006;259(2):260–8.PubMedCrossRef Biswas R, Voggu L, Simon UK, Hentschel P, Thumm G, Götz F. Activity of the major staphylococcal autolysin Atl. FEMS Microbiol Lett. 2006;259(2):260–8.PubMedCrossRef
61.
go back to reference Chavakis T, Wiechmann K, Preissner KT, 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. 2005;94(2):278–85.PubMed Chavakis T, Wiechmann K, Preissner KT, 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. 2005;94(2):278–85.PubMed
63.
go back to reference •• Wang R, Braughton KR, Kretschmer D, Bach TH, Queck SY, Li M, et al. Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA. Nat Med. 2007;13(12):1510–4. Identified PSMs as a major determinant of S. aureus virulence including leukocyte lysis. Expression of PSMs was found to be tightly regulated through the agr quorum-sensing system. PubMedCrossRef •• Wang R, Braughton KR, Kretschmer D, Bach TH, Queck SY, Li M, et al. Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA. Nat Med. 2007;13(12):1510–4. Identified PSMs as a major determinant of S. aureus virulence including leukocyte lysis. Expression of PSMs was found to be tightly regulated through the agr quorum-sensing system. PubMedCrossRef
65.
go back to reference Clauditz A, Resch A, Wieland KP, Peschel A, Götz F. Staphyloxanthin plays a role in the fitness of Staphylococcus aureus and its ability to cope with oxidative stress. Infect Immun. 2006;74(8):4950–3.PubMedPubMedCentralCrossRef Clauditz A, Resch A, Wieland KP, Peschel A, Götz F. Staphyloxanthin plays a role in the fitness of Staphylococcus aureus and its ability to cope with oxidative stress. Infect Immun. 2006;74(8):4950–3.PubMedPubMedCentralCrossRef
66.
go back to reference • Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, et al. Neutrophil extracellular traps kill bacteria. Science. 2004;303(5663):1532–5. Described the characteristics and release of neutrophil extracellular traps (NETs), which are granule proteins and chromatin that are released extracellularly to degrade virulence factors and immobilize bacteria for phagocytic clearance. PubMedCrossRef • Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, et al. Neutrophil extracellular traps kill bacteria. Science. 2004;303(5663):1532–5. Described the characteristics and release of neutrophil extracellular traps (NETs), which are granule proteins and chromatin that are released extracellularly to degrade virulence factors and immobilize bacteria for phagocytic clearance. PubMedCrossRef
71.
go back to reference • Thurlow LR, Hanke ML, Fritz T, Angle A, Aldrich A, Williams SH, et al. Staphylococcus aureus biofilms prevent macrophage phagocytosis and attenuate inflammation in vivo. J Immunol. 2011;186(11):6585–96. https://doi.org/10.4049/jimmunol.1002794. Using a mouse model of catheter-associated infection, the authors showed that S. aureus biofilm was capable of attenuating inflammatory cytokine production and skewing the immune response towards a pro-fibrotic M2 macrophage phenotype. PubMedPubMedCentralCrossRef • Thurlow LR, Hanke ML, Fritz T, Angle A, Aldrich A, Williams SH, et al. Staphylococcus aureus biofilms prevent macrophage phagocytosis and attenuate inflammation in vivo. J Immunol. 2011;186(11):6585–96. https://​doi.​org/​10.​4049/​jimmunol.​1002794. Using a mouse model of catheter-associated infection, the authors showed that S. aureus biofilm was capable of attenuating inflammatory cytokine production and skewing the immune response towards a pro-fibrotic M2 macrophage phenotype. PubMedPubMedCentralCrossRef
74.
go back to reference • Heim CE, Vidlak D, Scherr TD, Kozel JA, Holzapfel M, Muirhead DE, et al. Myeloid-derived suppressor cells contribute to Staphylococcus aureus orthopedic biofilm infection. J Immunol. 2014;192(8):3778–92. https://doi.org/10.4049/jimmunol.1303408. In a murine model of prosthetic joint infection (PJI), the authors demonstrated that MDSCs actively suppressed T cell recruitment and proinflammatory cytokine production at the site of infection, thereby facilitating S. aureus biofilm persistence and proliferation. PubMedPubMedCentralCrossRef • Heim CE, Vidlak D, Scherr TD, Kozel JA, Holzapfel M, Muirhead DE, et al. Myeloid-derived suppressor cells contribute to Staphylococcus aureus orthopedic biofilm infection. J Immunol. 2014;192(8):3778–92. https://​doi.​org/​10.​4049/​jimmunol.​1303408. In a murine model of prosthetic joint infection (PJI), the authors demonstrated that MDSCs actively suppressed T cell recruitment and proinflammatory cytokine production at the site of infection, thereby facilitating S. aureus biofilm persistence and proliferation. PubMedPubMedCentralCrossRef
80.
go back to reference Jensen LK, Jensen HE, Koch J, Bjarnsholt T, Eickhardt S, Shirtliff M. Specific antibodies to Staphylococcus aureus biofilm are present in serum from pigs with osteomyelitis. In Vivo. 2015;29(5):555–60.PubMed Jensen LK, Jensen HE, Koch J, Bjarnsholt T, Eickhardt S, Shirtliff M. Specific antibodies to Staphylococcus aureus biofilm are present in serum from pigs with osteomyelitis. In Vivo. 2015;29(5):555–60.PubMed
86.
go back to reference • Nishitani K, Beck CA, Rosenberg AF, Kates SL, Schwarz EM, Daiss JL. A diagnostic serum antibody test for patients with Staphylococcus aureus osteomyelitis. Clin Orthop Relat Res. 2015;473(9):2735–49. https://doi.org/10.1007/s11999-015-4354-2. Described the serum host antibody response in patients with deep muscolskeletal infection with S. aureus versus healthy controls. No single titer yielded diagnostic significance; however, using a combination of host antibodies may provide diagnostic utility for ongoing infection. PubMedPubMedCentralCrossRef • Nishitani K, Beck CA, Rosenberg AF, Kates SL, Schwarz EM, Daiss JL. A diagnostic serum antibody test for patients with Staphylococcus aureus osteomyelitis. Clin Orthop Relat Res. 2015;473(9):2735–49. https://​doi.​org/​10.​1007/​s11999-015-4354-2. Described the serum host antibody response in patients with deep muscolskeletal infection with S. aureus versus healthy controls. No single titer yielded diagnostic significance; however, using a combination of host antibodies may provide diagnostic utility for ongoing infection. PubMedPubMedCentralCrossRef
90.
go back to reference Vuong C, Saenz HL, Götz F, Otto M. Impact of the agr quorum-sensing system on adherence to polystyrene in Staphylococcus aureus. J Infect Dis. 2000;182(6):1688–93.PubMedCrossRef Vuong C, Saenz HL, Götz F, Otto M. Impact of the agr quorum-sensing system on adherence to polystyrene in Staphylococcus aureus. J Infect Dis. 2000;182(6):1688–93.PubMedCrossRef
91.
go back to reference Vuong C, Kocianova S, Yao Y, Carmody AB, Otto M. Increased colonization of indwelling medical devices by quorum-sensing mutants of Staphylococcus epidermidis in vivo. J Infect Dis. 2004;190(8):1498–505.PubMedCrossRef Vuong C, Kocianova S, Yao Y, Carmody AB, Otto M. Increased colonization of indwelling medical devices by quorum-sensing mutants of Staphylococcus epidermidis in vivo. J Infect Dis. 2004;190(8):1498–505.PubMedCrossRef
96.
go back to reference Darouiche RO. Treatment of infections associated with surgical implants. N Engl J Med. 2004;350(14):1422–9.PubMedCrossRef Darouiche RO. Treatment of infections associated with surgical implants. N Engl J Med. 2004;350(14):1422–9.PubMedCrossRef
97.
go back to reference •• de Mesy Bentley KL, Trombetta R, Nishitani K, Bello-Irizarry SN, Ninomiya M, Zhang 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. 2017;32(5):985–90. https://doi.org/10.1002/jbmr.3055. Used a murine implant-associated infection model to show that S. aureus was able to deform, enter the canalicular system via asymmetric binary fission, and migrate toward osteocyte lacunae via proliferation at the leading edge, providing a novel reservoir to protect S. aureus from host immunity. PubMedPubMedCentralCrossRef •• de Mesy Bentley KL, Trombetta R, Nishitani K, Bello-Irizarry SN, Ninomiya M, Zhang 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. 2017;32(5):985–90. https://​doi.​org/​10.​1002/​jbmr.​3055. Used a murine implant-associated infection model to show that S. aureus was able to deform, enter the canalicular system via asymmetric binary fission, and migrate toward osteocyte lacunae via proliferation at the leading edge, providing a novel reservoir to protect S. aureus from host immunity. PubMedPubMedCentralCrossRef
99.
go back to reference Nishitani K, Bello-Irizarry SN, de Mesy Bentley K, Daiss JL, Schwarz EM. The role of the immune system and bone cells in acute and chronic osteomyelitis. Osteoimmunology. 2016; 2nd ed (Chapter 16):283–95. Nishitani K, Bello-Irizarry SN, de Mesy Bentley K, Daiss JL, Schwarz EM. The role of the immune system and bone cells in acute and chronic osteomyelitis. Osteoimmunology. 2016; 2nd ed (Chapter 16):283–95.
103.
105.
go back to reference Jørgensen NP, Skovdal SM, Meyer RL, Dagnæs-Hansen F, Fuursted K, Petersen E. Rifampicin-containing combinations are superior to combinations of vancomycin, linezolid and daptomycin against Staphylococcus aureus biofilm infection in vivo and in vitro. Pathog Dis. 2016;74(4):ftw019. https://doi.org/10.1093/femspd/ftw019.PubMedCrossRef Jørgensen NP, Skovdal SM, Meyer RL, Dagnæs-Hansen F, Fuursted K, Petersen E. Rifampicin-containing combinations are superior to combinations of vancomycin, linezolid and daptomycin against Staphylococcus aureus biofilm infection in vivo and in vitro. Pathog Dis. 2016;74(4):ftw019. https://​doi.​org/​10.​1093/​femspd/​ftw019.PubMedCrossRef
109.
go back to reference Zimmerli W, Widmer AF, Blatter M, Frei R, Ochsner PE. Role of rifampin for treatment of orthopedic implant-related staphylococcal infections: a randomized controlled trial. Foreign-body infection (FBI) study group. JAMA. 1998;279(19):1537–41.PubMedCrossRef Zimmerli W, Widmer AF, Blatter M, Frei R, Ochsner PE. Role of rifampin for treatment of orthopedic implant-related staphylococcal infections: a randomized controlled trial. Foreign-body infection (FBI) study group. JAMA. 1998;279(19):1537–41.PubMedCrossRef
114.
go back to reference • Fowler VG, Allen KB, Moreira ED, Moustafa M, Isgro F, Boucher HW, et al. Effect of an investigational vaccine for preventing Staphylococcus aureus infections after cardiothoracic surgery: a randomized trial. JAMA. 2013;309(13):1368–78. https://doi.org/10.1001/jama.2013.3010. Phase 2b/3 trial of vaccine from Merck (V710), targeting IsdB in patients undergoing cardiothoracic surgery. V710 failed to reduce infection rates or mortality. Moreover, patients who did get infected were more likely to die in the vaccine group, suggesting that this vaccine may actually impair host immunity against sepsis. PubMedCrossRef • Fowler VG, Allen KB, Moreira ED, Moustafa M, Isgro F, Boucher HW, et al. Effect of an investigational vaccine for preventing Staphylococcus aureus infections after cardiothoracic surgery: a randomized trial. JAMA. 2013;309(13):1368–78. https://​doi.​org/​10.​1001/​jama.​2013.​3010. Phase 2b/3 trial of vaccine from Merck (V710), targeting IsdB in patients undergoing cardiothoracic surgery. V710 failed to reduce infection rates or mortality. Moreover, patients who did get infected were more likely to die in the vaccine group, suggesting that this vaccine may actually impair host immunity against sepsis. PubMedCrossRef
116.
go back to reference Shinefield H, Black S, Fattom A, Horwith G, Rasgon S, Ordonez J, et al. Use of a Staphylococcus aureus conjugate vaccine in patients receiving hemodialysis. N Engl J Med. 2002;346(7):491–6.PubMedCrossRef Shinefield H, Black S, Fattom A, Horwith G, Rasgon S, Ordonez J, et al. Use of a Staphylococcus aureus conjugate vaccine in patients receiving hemodialysis. N Engl J Med. 2002;346(7):491–6.PubMedCrossRef
118.
go back to reference Varrone JJ, de Mesy Bentley KL, Bello-Irizarry SN, Nishitani K, Mack S, Hunter JG, et al. Passive immunization with anti-glucosaminidase monoclonal antibodies protects mice from implant-associated osteomyelitis by mediating opsonophagocytosis of Staphylococcus aureus megaclusters. J Orthop Res. 2014;32(10):1389–96. https://doi.org/10.1002/jor.22672.PubMedPubMedCentralCrossRef Varrone JJ, de Mesy Bentley KL, Bello-Irizarry SN, Nishitani K, Mack S, Hunter JG, et al. Passive immunization with anti-glucosaminidase monoclonal antibodies protects mice from implant-associated osteomyelitis by mediating opsonophagocytosis of Staphylococcus aureus megaclusters. J Orthop Res. 2014;32(10):1389–96. https://​doi.​org/​10.​1002/​jor.​22672.PubMedPubMedCentralCrossRef
119.
go back to reference • Yokogawa N, Ishikawa M, Nishitani K, Beck CA, Tsuchiya H, Mesfin A, et al. Immunotherapy synergizes with debridement and antibiotic therapy in a murine 1-stage exchange model of MRSA implant-associated osteomyelitis. J Orthop Res. 2018; https://doi.org/10.1002/jor.23801. Using a murine implant-associated infection model, the authors found that immunotherapy with anti-Gmd monoclonal antibodies inhibited SACs while vancomycin reduced CFUs on the implant. Combination therapy provided the best results in soft tissue and implant infection control. • Yokogawa N, Ishikawa M, Nishitani K, Beck CA, Tsuchiya H, Mesfin A, et al. Immunotherapy synergizes with debridement and antibiotic therapy in a murine 1-stage exchange model of MRSA implant-associated osteomyelitis. J Orthop Res. 2018; https://​doi.​org/​10.​1002/​jor.​23801. Using a murine implant-associated infection model, the authors found that immunotherapy with anti-Gmd monoclonal antibodies inhibited SACs while vancomycin reduced CFUs on the implant. Combination therapy provided the best results in soft tissue and implant infection control.
120.
go back to reference •• Lehar SM, Pillow T, Xu M, Staben L, Kajihara KK, Vandlen R, et al. Novel antibody-antibiotic conjugate eliminates intracellular S. aureus. Nature. 2015;527(7578):323–8. https://doi.org/10.1038/nature16057. The authors created an antibody-antibiotic conjugate (AAC) that consisted of a monoclonal antibody that recognizes the alpha-O-linked N-acetylglucosamine sugars on wall teichoic acids (WTAs) bound to rifamycin class derivative antibiotic to target intracellular S. aureus . This AAC demonstrated improved results versus systemic vancomycin alone in a murine MRSA hematogenous infection model. PubMedCrossRef •• Lehar SM, Pillow T, Xu M, Staben L, Kajihara KK, Vandlen R, et al. Novel antibody-antibiotic conjugate eliminates intracellular S. aureus. Nature. 2015;527(7578):323–8. https://​doi.​org/​10.​1038/​nature16057. The authors created an antibody-antibiotic conjugate (AAC) that consisted of a monoclonal antibody that recognizes the alpha-O-linked N-acetylglucosamine sugars on wall teichoic acids (WTAs) bound to rifamycin class derivative antibiotic to target intracellular S. aureus . This AAC demonstrated improved results versus systemic vancomycin alone in a murine MRSA hematogenous infection model. PubMedCrossRef
125.
go back to reference • Wafa H, Grimer RJ, Reddy K, Jeys L, Abudu A, Carter SR, et al. Retrospective evaluation of the incidence of early periprosthetic infection with silver-treated endoprostheses in high-risk patients: case-control study. Bone Joint J. 2015;97-B(2):252–7. https://doi.org/10.1302/0301-620X.97B2.34554. A case-control clinical study using silver-coated megaprosthesis (Alguna). The silver-coated prosthesis had reduced rates of postoperative infection (11.8 versus 22.4%) and had improved success after debridement and implant retention relative to titanium implants. PubMedCrossRef • Wafa H, Grimer RJ, Reddy K, Jeys L, Abudu A, Carter SR, et al. Retrospective evaluation of the incidence of early periprosthetic infection with silver-treated endoprostheses in high-risk patients: case-control study. Bone Joint J. 2015;97-B(2):252–7. https://​doi.​org/​10.​1302/​0301-620X.​97B2.​34554. A case-control clinical study using silver-coated megaprosthesis (Alguna). The silver-coated prosthesis had reduced rates of postoperative infection (11.8 versus 22.4%) and had improved success after debridement and implant retention relative to titanium implants. PubMedCrossRef
128.
go back to reference Schierholz JM, Lucas LJ, Rump A, Pulverer G. Efficacy of silver-coated medical devices. J Hosp Infect. 1998;40(4):257–62.PubMedCrossRef Schierholz JM, Lucas LJ, Rump A, Pulverer G. Efficacy of silver-coated medical devices. J Hosp Infect. 1998;40(4):257–62.PubMedCrossRef
130.
Metadata
Title
Staphylococcus aureus Evasion of Host Immunity in the Setting of Prosthetic Joint Infection: Biofilm and Beyond
Authors
Benjamin F. Ricciardi
Gowrishankar Muthukrishnan
Elysia Masters
Mark Ninomiya
Charles C. Lee
Edward M. Schwarz
Publication date
01-09-2018
Publisher
Springer US
Published in
Current Reviews in Musculoskeletal Medicine / Issue 3/2018
Electronic ISSN: 1935-9748
DOI
https://doi.org/10.1007/s12178-018-9501-4

Other articles of this Issue 3/2018

Current Reviews in Musculoskeletal Medicine 3/2018 Go to the issue

Foot and Ankle Trauma (G Moloney, section editor)

Limited Approaches to Calcaneal Fractures

Foot and Ankle Trauma (G Moloney, section editor)

Special Considerations in the Management of Diabetic Ankle Fractures

PCL Update (K Jones and M Alaia, section editors)

Graft Considerations in Posterior Cruciate Ligament Reconstruction

Foot and Ankle Trauma (G Moloney, section editor)

Retrograde Hindfoot Nailing for Acute Trauma

Prosthetic Joint Infection (S Nodzo and N Frisch, section editors)

Two-Stage Revision Arthroplasty for the Treatment of Prosthetic Joint Infection