title: Effect of biofilms on recalcitrance of staphylococcal joint infection to antibiotic treatment.
abstract: 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 show that methicillin-resistant Staphylococcus aureus, a major cause of joint infections, forms exceptionally strong biofilmlike aggregates in human synovial fluid (SF), to an extent significantly exceeding biofilm formation observed in growth medium or serum. Screening a transposon bank identified bacterial fibronectin- and fibrinogen-binding proteins as important for the formation of macroscopic clumps in SF, suggesting an important role of fibrin-containing clots in the formation of bacterial aggregates during joint infection. Pretreatment of SF with plasmin led to a strongly reduced formation of aggregates and increased susceptibility to antibiotics. These results give important insight into the pathogenesis of staphylococcal joint infection and the mechanisms underlying resistance to treatment. Furthermore, they point toward a potential novel approach for treating joint infections.
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Department of Orthopedic Surgery, Thomas Jefferson University.
authors.forename: Sana
authors.initials: S
authors.lastname: Dastgheyb
authors.affiliation: The Rothman Institute, Philadelphia, Pennsylvania.
authors.forename: Javad
authors.initials: J
authors.lastname: Parvizi
authors.affiliation: Department of Orthopedic Surgery, Thomas Jefferson University.
authors.forename: Irving M
authors.initials: IM
authors.lastname: Shapiro
authors.affiliation: Department of Orthopedic Surgery, Thomas Jefferson University.
authors.forename: Noreen J
authors.initials: NJ
authors.lastname: Hickok
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Michael
authors.initials: M
authors.lastname: Otto
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001170:Arthritis, Infectious / Q000382:microbiology*; D018441:Biofilms / Q000254:growth & development*; D015169:Colony Count, Microbial; D005341:Fibrinolysin / Q000494:pharmacology; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development*; D008954:Models, Biological; D013203:Staphylococcal Infections / Q000382:microbiology*; D013582:Synovial Fluid / Q000382:microbiology / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D005341:Fibrinolysin
keywords: MRSA; Staphylococcus aureus; antibiotic resistance; biofilm; joint infection; septic arthritis