title: Inhibition by quinolones of DNA gyrase from Staphylococcus aureus.
abstract: In order to clarify the mechanism of action of quinolones against Staphylococcus aureus, the subunit A and B proteins of DNA gyrase were separately purified from a crude extract of S. aureus FDA 209-P. The reconstituted enzyme exhibited ATP-dependent DNA supercoiling activity. The inhibitory effects of quinolones on the supercoiling activity of the purified enzyme were measured by the quantitative electrophoresis method (17), using plasmid DNA, pBR322 or pUB110, as substrates and expressed as the 50% inhibitory concentrations (IC50s). The IC50s of ofloxacin, DR-3355 (l-ofloxacin), ciprofloxacin, tosufloxacin, sparfloxacin, and DS-4524, a new quinolone derivative, for pBR322 were 63.0, 37.8, 30.5, 46.0, 28.5, and 3.2 micrograms/ml, respectively. These values were closely correlated with antibacterial activity (MIC), with correlation coefficients of 0.953 for pBR322 and 0.938 for pUB110. These results indicate that, in S. aureus, as in gram-negative bacteria, DNA gyrase is likely to be a major target enzyme of quinolones.
authors.affiliation: Exploratory Research Laboratories I, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: Y
authors.initials: Y
authors.lastname: Kimura
authors.forename: I
authors.initials: I
authors.lastname: Hayakawa
authors.forename: Y
authors.initials: Y
authors.lastname: Osada
authors.forename: T
authors.initials: T
authors.lastname: Nishino
mesh_terms: D042462:4-Quinolones; D000890:Anti-Infective Agents / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000096:biosynthesis; D004278:DNA, Superhelical / Q000096:biosynthesis; D008826:Microbial Sensitivity Tests; D010957:Plasmids; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D059005:Topoisomerase II Inhibitors
chemical_list: D042462:4-Quinolones; D000890:Anti-Infective Agents; D004269:DNA, Bacterial; D004278:DNA, Superhelical; D059005:Topoisomerase II Inhibitors