title: A triclosan-ciprofloxacin cross-resistant mutant strain of Staphylococcus aureus displays an alteration in the expression of several cell membrane structural and functional genes.
abstract: Triclosan is an antimicrobial agent found in many consumer products. Triclosan inhibits the bacterial fatty acid biosynthetic enzyme, enoyl-ACP reductase (FabI). Decreased susceptibility to triclosan correlates with ciprofloxacin resistance in several bacteria. In these bacteria, resistance to both drugs maps to genes encoding multi-drug efflux pumps. The focus of this study was to determine whether triclosan resistance contributes to ciprofloxacin resistance in Staphylococcus aureus. In S. aureus, triclosan resistance maps to a fabI homolog and ciprofloxacin resistance maps to genes encoding DNA gyrase, topoisomerase IV and to the multi-drug efflux pump, NorA. Using a norA overexpressing mutant, we demonstrated that upregulation of NorA does not lead to triclosan resistance. To further investigate triclosan/ciprofloxacin resistance in S. aureus, we isolated triclosan/ciprofloxacin-resistant mutants. The mutants were screened for mutations in the genes encoding the targets of triclosan and ciprofloxacin. One mutant, JJ5, was wild-type for all sequences analyzed. We next monitored the efflux of triclosan from JJ5 and determined that triclosan resistance in the mutant was not due to active efflux of the drug. Finally, gene expression profiling demonstrated that an alteration in cell membrane structural and functional gene expression is likely responsible for triclosan and ciprofloxacin resistance in JJ5.
authors.affiliation: Pace University, Department of Biology and Health Sciences, 1 Pace Plaza, New York, NY 10038, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Tkachenko
authors.forename: Jessica
authors.initials: J
authors.lastname: Shepard
authors.forename: Virginie M
authors.initials: VM
authors.lastname: Aris
authors.forename: Amy
authors.initials: A
authors.lastname: Joy
authors.forename: Anangely
authors.initials: A
authors.lastname: Bello
authors.forename: Indira
authors.initials: I
authors.lastname: Londono
authors.forename: Jehona
authors.initials: J
authors.lastname: Marku
authors.forename: Patricia
authors.initials: P
authors.lastname: Soteropoulos
authors.forename: Marcy A
authors.initials: MA
authors.lastname: Peteroy-Kelly
mesh_terms: D001692:Biological Transport; D002462:Cell Membrane / Q000187:drug effects; D002939:Ciprofloxacin / Q000493:pharmacokinetics / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D005798:Genes, Bacterial; D009154:Mutation; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism; D014260:Triclosan / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D014260:Triclosan; D002939:Ciprofloxacin