Impact of vancomycin on sarA-mediated biofilm formation: Role in persistent endovascular infections due to methicillin-resistant staphylococcus aureus

Wessam Abdelhady, Arnold S. Bayer, Kati Seidl, Derek E. Moormeier, Kenneth W Bayles, Ambrose Cheung, Michael R. Yeaman, Yan Q. Xiong

Research output: Contribution to journalArticle

32 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1231-1240
Number of pages10
JournalJournal of Infectious Diseases
Volume209
Issue number8
DOIs
StatePublished - Apr 15 2014

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Keywords

  • MRSA endocarditis
  • biofilm formation
  • sarA

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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