title: Quinolone-resistant mutants of escherichia coli DNA topoisomerase IV parC gene.
abstract: Escherichia coli quinolone-resistant strains with mutations of the parC gene, which codes for a subunit of topoisomerase IV, were isolated from a quinolone-resistant gyrA mutant of DNA gyrase. Quinolone-resistant parC mutants were also identified among the quinolone-resistant clinical strains. The parC mutants became susceptible to quinolones by introduction of a parC+ plasmid. Introduction of the multicopy plasmids carrying the quinolone-resistant parC mutant gene resulted in an increase in MICs of quinolones for the parC+ and quinolone-resistant gyrA strain. Nucleotide sequences of the quinolone-resistant parC mutant genes were determined, and missense mutations at position Gly-78, Ser-80, or Glu-84, corresponding to those in the quinolone-resistance-determining region of DNA gyrase, were identified. These results indicate that topoisomerase IV is a target of quinolones in E. coli and suggest that the susceptibility of E. coli cells to quinolones is determined by sensitivity of the targets, DNA gyrase and topoisomerase IV.
authors.affiliation: Department of Molecular Biology, University of Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kumagai
authors.forename: J I
authors.initials: JI
authors.lastname: Kato
authors.forename: K
authors.initials: K
authors.lastname: Hoshino
authors.forename: T
authors.initials: T
authors.lastname: Akasaka
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: H
authors.initials: H
authors.lastname: Ikeda
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D001483:Base Sequence; D003001:Cloning, Molecular; D003470:Culture Media; D027101:DNA Topoisomerase IV; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004269:DNA, Bacterial / Q000187:drug effects / Q000235:genetics*; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics*; D004927:Escherichia coli Infections / Q000382:microbiology; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D015242:Ofloxacin / Q000494:pharmacology; D010957:Plasmids
chemical_list: D000890:Anti-Infective Agents; D003470:Culture Media; D004269:DNA, Bacterial; D015242:Ofloxacin; D027101:DNA Topoisomerase IV; D004250:DNA Topoisomerases, Type II