title: Multidrug efflux pump overexpression in Staphylococcus aureus after single and multiple in vitro exposures to biocides and dyes.
abstract: Biocides and dyes are commonly employed in hospital and laboratory settings. Many of these agents are substrates for multiple-drug resistance (MDR)-conferring efflux pumps of both Gram-positive and Gram-negative organisms. Several such pumps have been identified in Staphylococcus aureus, and mutants overexpressing the NorA and MepA MDR pumps following exposure to fluoroquinolones have been identified. The effect of exposure to low concentrations of biocides and dyes on the expression of specific pump genes has not been evaluated. Using quantitative reverse-transcription PCR we found that exposure of clinical isolates to low concentrations of a variety of biocides and dyes in a single step, or to gradually increasing concentrations over several days, resulted in the appearance of mutants overexpressing mepA, mdeA, norA and norC, with mepA overexpression predominating. Overexpression was frequently associated with promoter-region or regulatory protein mutations. Mutants having significant increases in MICs of common pump substrates but no changes in expression of studied pump genes were also observed; in these cases changes in expression of as-yet-unidentified MDR pump genes may have occurred. Strains of S. aureus that exist in relatively protected environments and are repeatedly exposed to sublethal concentrations of biocides can develop efflux-related resistance to those agents, and acquisition of such strains poses a threat to patients treated with antimicrobial agents that are also substrates for those pumps, such as ciprofloxacin and moxifloxacin.
authors.affiliation: École Supérieure de Microbiologie et Sécurité Alimentaire de Brest, Université de Bretagne Occidentale, Technopôle Brest-Iroise, 29280 Plouzané, France.|John D. Dingell Department of Veterans Affairs Medical Center, Detroit, MI 48201, USA.
authors.forename: Aurélie A
authors.initials: AA
authors.lastname: Huet
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Raygada
authors.affiliation: John D. Dingell Department of Veterans Affairs Medical Center, Detroit, MI 48201, USA.
authors.forename: Kabir
authors.initials: K
authors.lastname: Mendiratta
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Seo
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Wayne State University School of Medicine, Detroit, MI 48201, USA.|John D. Dingell Department of Veterans Affairs Medical Center, Detroit, MI 48201, USA.
authors.forename: Glenn W
authors.initials: GW
authors.lastname: Kaatz
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D004396:Coloring Agents / Q000494:pharmacology*; D004202:Disinfectants / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects* / Q000235:genetics; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D008826:Microbial Sensitivity Tests; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation; D012329:RNA, Bacterial / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004396:Coloring Agents; D004202:Disinfectants; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012329:RNA, Bacterial