title: Sitafloxacin: antimicrobial activity against ciprofloxacin-selected laboratory mutants of Mycoplasma genitalium and inhibitory activity against its DNA gyrase and topoisomerase IV.
abstract: A sitafloxacin regimen is highly effective on Mycoplasma genitalium infections, including those caused by the mycoplasmas harboring mutant topoisomerase IV with a quinolone resistance-associated amino acid change in ParC. In this study, we evaluated sitafloxacin antimicrobial activities against M. genitalium, including the mycoplasmas with decreased susceptibilities to quinolones, by determining minimum inhibitory concentrations (MICs) for the strain ATCC 33530 and its 3 ciprofloxacin-selected mutants, for which ciprofloxacin MICs were 8-16 times higher than that for their parent strain. We also evaluated inhibitory activities against the target enzymes of M. genitalium by determining concentrations required to inhibit 50% (IC50) of the supercoiling activity of the recombinant wild-type DNA gyrase and the decatenating activities of the recombinant wild-type topoisomerase IV and the 2 types of mutant topoisomerase IV with a single amino acid change in ParC. Sitafloxacin MICs were 0.125 for the parent strain and 0.125-0.25 μg/ml for the mutants. Sitafloxacin IC50s were 3.12 for the supercoiling activity of the wild-type DNA gyrase and 2.98 μg/ml for the decatenating activity of the wild-type topoisomerase IV. Its IC50s for the decatenating activity of the mutant topoisomerase IV harboring an amino acid change in ParC were 15.1 for Gly-81 → Cys and 7.92 μg/ml for Asp-87 → Tyr. Sitafloxacin was highly active against ciprofloxacin-selected mutants of M. genitalium and possessed intense inhibitory activities not only against wild-type DNA gyrase and topoisomerase IV but also against mutant topoisomerase IV containing ParC with a quinolone resistance-associated amino acid change. Sitafloxacin could be a promising agent for M. genitalium infections.
authors.affiliation: Department of Urology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, Gifu 501-1194, Japan. Electronic address: deguchit@gifu-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Deguchi
authors.affiliation: Department of Urology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, Gifu 501-1194, Japan.
authors.forename: Mina
authors.initials: M
authors.lastname: Kikuchi
authors.affiliation: Department of Urology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, Gifu 501-1194, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Yasuda
authors.affiliation: iClinic, 5-9-6 Naga-machi, Taihaku-ku, Sendai 982-0011, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Ito
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology; D027081:DNA Gyrase / Q000187:drug effects; D027101:DNA Topoisomerase IV / Q000187:drug effects; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics*; D009175:Mycoplasma Infections / Q000382:microbiology; D045704:Mycoplasma genitalium / Q000187:drug effects* / Q000235:genetics*; D059005:Topoisomerase II Inhibitors / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D024841:Fluoroquinolones; D059005:Topoisomerase II Inhibitors; D002939:Ciprofloxacin; C076246:sitafloxacin; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase
keywords: DNA gyrase; Mycoplasma genitalium; ParC; Sitafloxacin; Topisomerase IV