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Biofilms cause recalcitrance of staphylococcal joint infection to antibiotic treatment

Thursday, September 17, 2015 — Poster Session II

12:00 p.m. – 1:30 p.m.
FAES Terrace


  • SS Dastgheyb
  • AE Villaruz
  • KL Le
  • VY Tan
  • AC Duong
  • SS Chatterjee
  • GY Cheung
  • HS Joo
  • J Parvizi
  • IM Shapiro
  • NJ Hickok
  • M Otto


The pathogenesis of joint infections is not well understood. In particular, we do not know why these infections respond poorly to antibiotic treatment. Here, we used an ex-vivo approach to investigate the bacterial factors contributing to joint infection by isolating uninfected synovial fluid (SF) from patients undergoing joint surgery. Even with antibiotic concentrations that far exceed the expected bactericidal levels, Staphylococcus aureus bacteria added to the synovial fluid samples were able to colonize model implant surfaces. We show that this phenotype is due to biofilm formation. We identified bacterial fibronectin- and fibrinogen-binding proteins as important for aggregation in SF, suggesting an important role of fibrin-containing clots in the formation of bacterial biofilm-like aggregates during joint infection. Pre-treatment of synovial fluid with plasmin led to a strongly reduced formation of aggregates and increased susceptibility to antibiotics. Furthermore, we found that low activity of the Agr regulatory system and subsequent low production of the phenol-soluble modulin (PSM) surfactant peptides cause agglomerates to grow to exceptional dimensions. Together, our findings support a two-step model of staphylococcal prosthetic joint infection: Interaction of S. aureus surface proteins with host matrix proteins such as fibrin initiates agglomeration; thereafter, the bacterial agglomerates grow to extremely large sizes owing to the lack of PSM expression under the specific conditions present in joints. Our findings provide a mechanistic explanation for the extreme resistance of joint infection to antibiotic treatment and have important implications for anti-staphylococcal therapeutic strategies.

Category: Microbiology and Infectious Diseases