title: Impact of vancomycin on sarA-mediated biofilm formation: role in persistent endovascular infections due to methicillin-resistant Staphylococcus aureus.
abstract: BACKGROUND
  Staphylococcus aureus is the most common cause of endovascular infections. The staphylococcal accessory regulator A locus (sarA) is a major virulence determinant that may potentially impact methicillin-resistant S. aureus (MRSA) persistence in such infections via its influence on biofilm formation.
  
  
  METHODS
  Two healthcare-associated MRSA isolates from patients with persistent bacteremia and 2 prototypical community-acquired MRSA strains, as well as their respective isogenic sarA mutants, were studied for in vitro biofilm formation, fibronectin-binding capacity, autolysis, and protease and nuclease activities. These assays were done in the presence or absence of sub-minimum inhibitory concentrations (MICs) of vancomycin. In addition, these strain pairs were compared for intrinsic virulence and responses to vancomycin therapy in experimental infective endocarditis, a prototypical biofilm model.
  
  
  RESULTS
  All sarA mutants displayed significantly reduced biofilm formation and binding to fibronectin but increased protease production in vitro, compared with their respective parental strains. Interestingly, exposure to sub-MICs of vancomycin significantly promoted biofilm formation and fibronectin-binding in parental strains but not in sarA mutants. In addition, all sarA mutants became exquisitely susceptible to vancomycin therapy, compared with their respective parental strains, in the infective endocarditis model.
  
  
  CONCLUSIONS
  These observations suggest that sarA activation is important in persistent MRSA endovascular infection, potentially in the setting of biofilm formation.
authors.affiliation: Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance.
authors.forename: Wessam
authors.initials: W
authors.lastname: Abdelhady
authors.forename: Arnold S
authors.initials: AS
authors.lastname: Bayer
authors.forename: Kati
authors.initials: K
authors.lastname: Seidl
authors.forename: Derek E
authors.initials: DE
authors.lastname: Moormeier
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Bayles
authors.forename: Ambrose
authors.initials: A
authors.lastname: Cheung
authors.forename: Michael R
authors.initials: MR
authors.lastname: Yeaman
authors.forename: Yan Q
authors.initials: YQ
authors.lastname: Xiong
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001329:Autolysis; D001426:Bacterial Proteins / Q000378:metabolism*; D018441:Biofilms / Q000187:drug effects*; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000472:pathogenicity / Q000502:physiology*; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D060888:Real-Time Polymerase Chain Reaction; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D014640:Vancomycin / Q000627:therapeutic use*; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005353:Fibronectins; C492107:SarA protein, Staphylococcus aureus; D014640:Vancomycin
keywords: MRSA endocarditis; biofilm formation; sarA