title: The effect of moxifloxacin on its target topoisomerases from Escherichia coli and Staphylococcus aureus.
abstract: The effect of moxifloxacin on its target enzymes was evaluated by three different approaches: (i) the MICs of moxifloxacin and nine other fluoroquinolones were determined for mutants of Escherichia coli (n = 13) and Staphylococcus aureus (n = 5) carrying different combinations of resistance mutations; (ii) the activity of moxifloxacin on isolated targets was determined as IC50 values for wild-type and mutant type II topoisomerases from E. coli; and (iii) the mutation frequencies were determined for two single-step mutants (MI with a Ser83-->Leu mutation in gyrA and WT-4 with a Ser80-->Ile mutation in parC) and their parent strain (WT). Of the quinolones tested, moxifloxacin was the only one showing an equivalent high activity against both targets. This is reflected by a comparable high susceptibility of the test strains of E. coli and S. aureus and by the IC50 values of moxifloxacin which were 50-90% lower than those of ciprofloxacin, norfloxacin and sparfloxacin for the wild-type and single mutant enzymes of gyrase and topoisomerase IV. However, double mutant GyrA was significantly more sensitive to moxifloxacin than to the other fluoroquinolones tested, while wild-type topoisomerase IV was two-fold more refractory. Mutation rates of WT, MI and WT-4 for ciprofloxacin and moxifloxacin were 5 x 10(-8) vs 4 x 10(-10); <6 x 10(-11) vs <6 x 10(-11); and 2 x 10(-6) vs 5 x 10(-7), respectively. These data indicate an equivalent high inhibitory activity of moxifloxacin on DNA gyrase and topoisomerase IV of E. coli.
authors.affiliation: Pharmaceutical Microbiology, University of Bonn, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Schedletzky
authors.forename: B
authors.initials: B
authors.lastname: Wiedemann
authors.forename: P
authors.initials: P
authors.lastname: Heisig
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D001372:Aza Compounds; D027081:DNA Gyrase; D027101:DNA Topoisomerase IV; D004264:DNA Topoisomerases, Type I / Q000187:drug effects* / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000187:drug effects* / Q000235:genetics; D004352:Drug Resistance, Microbial / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D024841:Fluoroquinolones; D005798:Genes, Bacterial; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D009154:Mutation; D011804:Quinolines; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics
chemical_list: D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D027101:DNA Topoisomerase IV; D004264:DNA Topoisomerases, Type I; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II; D000077266:Moxifloxacin