Quinolone-resistant mutants of escherichia coli DNA topoisomerase IV parC gene.
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.
Kumagai
Y
Y
Department of Molecular Biology, University of Tokyo, Japan.
Kato
J I
JI
Hoshino
K
K
Akasaka
T
T
Sato
K
K
Ikeda
H
H
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
D000890:Anti-Infective Agents; D003470:Culture Media; D004269:DNA, Bacterial; D015242:Ofloxacin; D027101:DNA Topoisomerase IV; D004250:DNA Topoisomerases, Type II