title: Activity of KB-5246 against outer membrane mutants of Escherichia coli and Salmonella typhimurium.
abstract: The inhibitory activity of KB-5246 against Escherichia coli DNA gyrase and the antibacterial activity and apparent uptake in E. coli and Salmonella typhimurium outer membrane mutants of KB-5246 were measured. The 50% inhibitory concentrations of KB-5246, ciprofloxacin, oflaxacin, and norfloxacin for E. coli KL-16 DNA gyrase were 0.72, 0.62, 0.84, and 1.16 micrograms/ml, respectively. The activity of KB-5246 was twofold lower against an OmpF-deficient mutant and twofold higher against a mutant which produced OmpF constitutively than against the parent with osmoregulated OmpF production. KB-5246 had twofold-higher activity against a deep rough mutant of S. typhimurium than against the parent. The apparent uptake of KB-5246 in the OmpF-deficient mutant was decreased and its uptake in the deep rough mutant was increased when compared with those in the parents. These results suggest that KB-5246 is taken up by porin and nonporin pathways and has strong inhibitory activity against DNA gyrase, resulting in potent antibacterial activity.
authors.affiliation: Episome Institute, Gunma, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kotera
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: S
authors.initials: S
authors.lastname: Mitsuhashi
mesh_terms: D042462:4-Quinolones; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003470:Culture Media; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D024841:Fluoroquinolones; D007202:Indicators and Reagents; D008826:Microbial Sensitivity Tests; D009154:Mutation; D043803:Phenalenes; D015363:Quinolones; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics; D059005:Topoisomerase II Inhibitors
chemical_list: D042462:4-Quinolones; D000890:Anti-Infective Agents; D001425:Bacterial Outer Membrane Proteins; D003470:Culture Media; D024841:Fluoroquinolones; D007202:Indicators and Reagents; D043803:Phenalenes; D015363:Quinolones; D059005:Topoisomerase II Inhibitors; C062447:KB 5246