title: Selection of moxifloxacin-resistant Staphylococcus aureus compared with five other fluoroquinolones.
abstract: Fluoroquinolone-resistant mutants were selected from Staphylococcus aureus NCTC 8532 (F77), and two GrlA mutants of F77 (F193 and F194) with moxifloxacin, sparfloxacin, ofloxacin, grepafloxacin, levofloxacin and trovafloxacin. For mutants selected from F77, moxifloxacin, grepafloxacin and sparfloxacin selected preferentially for mutations in gyrA (Glu-88-->Lys). Ofloxacin and trovafloxacin selected most commonly for mutations in grlA, conferring substitutions for Ser-80. Three mutants of F77 were shown to have substitutions in both GrlA (Phe-80) and GyrA (Lys-88). Of the mutants selected from F193 (GrlA Phe-80), restriction fragment length polymorphism analysis of gyrA showed that 76/94 had a mutation at codon 84; those analysed in detail all had the substitution Ser-->Leu. Two mutants selected with grepafloxacin contained the substitution Lys-88. One mutant selected with trovafloxacin contained a novel mutation in gyrA substituting Gly-82-->Cys. Of the mutants selected from F194 (GrlA Tyr-80), 6/8 had a mutation in gyrA codon 84; of which three contained Leu. The MICs of most agents for mutants selected from F193 and F194 were similar, irrespective of the mutation selected. No mutants had any changes in grlB, and only one had a mutation in gyrB giving rise to the novel substitution Asp-437-->His. The mutations arising in first-step mutants were influenced by the fluoroquinolone used for selection. The phenotypes and genotypes of second-step mutants, derived from mutants with existing mutations in grlA, were similar, regardless of the selecting antibiotic.
authors.affiliation: Antimicrobial Agents Research Group, Division of Immunity and Infection, The Medical School, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Griggs
authors.forename: Herida
authors.initials: H
authors.lastname: Marona
authors.forename: Laura J V
authors.initials: LJ
authors.lastname: Piddock
mesh_terms: D001372:Aza Compounds / Q000494:pharmacology*; D004352:Drug Resistance, Microbial / Q000235:genetics; D024841:Fluoroquinolones / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests / Q000379:methods; D000077266:Moxifloxacin; D009154:Mutation; D011804:Quinolines / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics
chemical_list: D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin