title: Mechanism of action of lomefloxacin.
abstract: The inhibition of supercoiling activity of reconstituted Escherichia coli DNA gyrase by lomefloxacin, ciprofloxacin, and norfloxacin was determined. The concentrations of quinolones needed to inhibit DNA synthesis in Escherichia coli, Enterobacter cloacae, Serratia marcescens, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus were also measured. The kinetics of uptake of [14C]lomefloxacin and unlabeled lomefloxacin into whole cells of E. coli KL-16 and S. aureus NCTC 8532 and the induction of RecA in E. coli GC2241 were assayed. All strains had wild-type susceptibilities to quinolones. The concentration of quinolones needed to inhibit DNA synthesis by 50% correlated with the MIC for members of the family Enterobacteriaceae and P. aeruginosa. The concentration of quinolones needed to inhibit DNA synthesis by 50% for late-logarithmic-phase S. aureus also correlated with the MIC, unlike the data from early-logarithmic-phase cultures. E. coli and S. aureus showed a similar pattern of uptake kinetics of [14C]lomefloxacin and unlabeled lomefloxacin, indicating that the difference in the susceptibilities of the two species is probably due to different target site affinities. Essentially, lomefloxacin was less active than ciprofloxacin and ofloxacin and had activity similar to those of norfloxacin and enoxacin.
authors.affiliation: Department of Medical Microbiology, University of Birmingham Medical School, United Kingdom.
authors.forename: L J
authors.initials: LJ
authors.lastname: Piddock
authors.forename: M C
authors.initials: MC
authors.lastname: Hall
authors.forename: R
authors.initials: R
authors.lastname: Wise
mesh_terms: D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D002939:Ciprofloxacin / Q000494:pharmacology; D004250:DNA Topoisomerases, Type II / Q000502:physiology; D004269:DNA, Bacterial / Q000032:analysis / Q000096:biosynthesis; D004278:DNA, Superhelical / Q000032:analysis; D024841:Fluoroquinolones; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D009643:Norfloxacin / Q000494:pharmacology; D015363:Quinolones; D011938:Rec A Recombinases / Q000096:biosynthesis
chemical_list: D000890:Anti-Infective Agents; D004269:DNA, Bacterial; D004278:DNA, Superhelical; D024841:Fluoroquinolones; D015363:Quinolones; D002939:Ciprofloxacin; D011938:Rec A Recombinases; D004250:DNA Topoisomerases, Type II; C053091:lomefloxacin; D009643:Norfloxacin