title: Impact of sarA on antibiotic susceptibility of Staphylococcus aureus in a catheter-associated in vitro model of biofilm formation.
abstract: Mutation of the staphylococcal accessory regulator (sarA) in Staphylococcus aureus limits but does not abolish the capacity of the organism to form a biofilm. As a first step toward determining whether this limitation is therapeutically relevant, we carried out in vitro studies comparing the relative susceptibility of an S. aureus clinical isolate (UAMS-1) and its isogenic sarA mutant (UAMS-929) in the specific context of a catheter-associated biofilm. The antibiotics tested were daptomycin, linezolid, and vancomycin, all of which were evaluated by using concentrations based on the MIC defined as the breakpoint for a susceptible strain of S. aureus (< or = 1.0, < or = 2.0, and < or = 4.0 microg/ml for daptomycin, vancomycin, and linezolid, respectively). Mutation of sarA had no significant impact on the MIC of UAMS-1 for any of the targeted antibiotics, as defined by Etest antimicrobial susceptibility testing. However, mutation of sarA did result in a significant increase in antimicrobial susceptibility to all targeted antibiotics when they were tested in the specific context of a biofilm. Additionally, whether susceptibility was assessed by using UAMS-1 or its sarA mutant, daptomycin was found to be more effective against established S. aureus biofilms than either linezolid or vancomycin.
authors.affiliation: Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205, USA.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Weiss
authors.forename: Horace J
authors.initials: HJ
authors.lastname: Spencer
authors.forename: Sonja J
authors.initials: SJ
authors.lastname: Daily
authors.forename: Brian D
authors.initials: BD
authors.lastname: Weiss
authors.forename: Mark S
authors.initials: MS
authors.lastname: Smeltzer
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000502:physiology*; D018441:Biofilms / Q000187:drug effects*; D002404:Catheterization / Q000009:adverse effects; D017576:Daptomycin / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009154:Mutation; D013211:Staphylococcus aureus / Q000187:drug effects*; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C492107:SarA protein, Staphylococcus aureus; D014640:Vancomycin; D017576:Daptomycin