Staphylococcus aureus in the synovial environment: Supporting long-term survival and insensitivity to antibiotics
Joint infection is a devastating condition faced by thousands each year in the United States alone. Currently, treatment for joint infection involves a combination of antibiotic treatment and irrigation/debridement of joint tissue; despite these interventions, infections often re-occur. With a limited therapeutic arsenal, it is imperative that studies be conducted to better understand the host-microbe interaction within the joint and to identify new areas for possible therapeutic targets. Within this thesis, ex vivo approaches are used to elucidate antibiotic efficacy, bacterial behavior, and biofilm formation in a simulated joint environment. Through direct collection of synovial fluid and exogenous addition of Staphylococcus aureus ( S. aureus), the pathogenesis of staphylococcal joint colonization is investigated. In synovial fluid samples collected from subjects that received antibiotic prophylaxis, for a 1-2 g pre-operative dose of cefazolin, ~200 &mgr;g/ml is measured in the joint fluid, indicating antibiotic penetrance into the joint fluid to achieve levels at least 100X greater than the reported MIC for S. aureus. Despite the presence of this high concentration of cefazolin, S. aureus is able to propagate, survive, and cause infection due to the formation of dense, protective aggregates and the induction of a biofilm-like phenotype. We show that standard antibiotics show limited efficacy in synovial fluid where even partial dispersal of the biofilm-like aggregates greatly increases antibiotic efficacy. In addition to determining the mechanism of antibiotic recalcitrance, we investigate the mechanism of biofilm-formation and staphylococcal virulence in synovial fluid at the levels of both transcription and translation. This thesis will serve as the base upon which research for improved treatment for joint infection may be conducted.
Dastgheyb, Sana, "Staphylococcus aureus in the synovial environment: Supporting long-term survival and insensitivity to antibiotics" (2014). ETD Collection for Thomas Jefferson University. AAI3705068.