title: Mechanisms of fluoroquinolone resistance in genetically related strains of Staphylococcus aureus.
abstract: Fluoroquinolone resistance in Staphylococcus aureus results from amino acid substitutions at particular locations in the DNA gyrase A and B subunits as well as in the topoisomerase IV A subunit and from NorA-mediated efflux. More than one resistance mechanism may be present in a single strain. Fluoroquinolone-resistant derivatives of SA-1199, a methicillin-susceptible S. aureus strain, were selected in vivo or in vitro, and their mechanisms of fluoroquinolone resistance were identified. We found that many of the resistance mechanisms described above can develop in derivatives of a single parent strain, either singly or in combination, and can arise in a single step. Variances in MICs for strains with the same apparent resistance mechanisms likely are due to the presence of new or undetected but established means of fluoroquinolone resistance. NorA-mediated resistance can occur in the apparent absence of topoisomerase mutations and in some strains may be the result of a promoter region mutation causing increased expression of norA. However, increased expression of norA can occur independently of this mutation, suggesting that a regulatory locus for this gene exists elsewhere on the chromosome.
authors.affiliation: Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. gkaatz@juno.com
authors.forename: G W
authors.initials: GW
authors.lastname: Kaatz
authors.forename: S M
authors.initials: SM
authors.lastname: Seo
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001483:Base Sequence; D004264:DNA Topoisomerases, Type I / Q000235:genetics / Q000378:metabolism; D004352:Drug Resistance, Microbial / Q000235:genetics; D015365:Enoxacin / Q000493:pharmacokinetics; D004996:Ethidium / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D009643:Norfloxacin / Q000494:pharmacology; D012150:Polymorphism, Restriction Fragment Length; D012110:Reserpine / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D015365:Enoxacin; D012110:Reserpine; D004264:DNA Topoisomerases, Type I; D004996:Ethidium; D009643:Norfloxacin