title: Inhibitory effects of ciprofloxacin and sparfloxacin on DNA gyrase purified from fluoroquinolone-resistant strains of methicillin-resistant Staphylococcus aureus.
abstract: The activities of new quinolones against 140 strains of methicillin-resistant Staphylococcus aureus were determined. From the relationship between the MICs of sparfloxacin and ciprofloxacin, fluoroquinolone-resistant S. aureus 6171 (MIC of sparfloxacin, 200 micrograms/ml; MIC of ciprofloxacin, 100 micrograms/ml) and fluoroquinolone-susceptible S. aureus FDA 209-P were selected for purification of the subunit A and B proteins of their DNA gyrases. The supercoiling activities of reconstituted ArBr (r, resistant) (from strain 6171) and ArBs (s, susceptible) gyrases were 40-fold more resistant to new quinolones than those of AsBs from FDA 209-P and AsBr gyrases. The 50% inhibitory doses of ciprofloxacin and sparfloxacin for AmBm (from mutant 19) and AmBs (m, moderately resistant) gyrases were 15- to 27-fold higher than those for AsBs and AsBm gyrases. These findings indicate that one of the resistance mechanisms of S. aureus against fluoroquinolones is a modification of the gyrase subunit A protein.
authors.affiliation: Department of Microbiology, Kyoto Pharmaceutical University, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Okuda
authors.forename: S
authors.initials: S
authors.lastname: Okamoto
authors.forename: M
authors.initials: M
authors.lastname: Takahata
authors.forename: T
authors.initials: T
authors.lastname: Nishino
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000378:metabolism / Q000494:pharmacology*; D004250:DNA Topoisomerases, Type II / Q000302:isolation & purification; D004278:DNA, Superhelical / Q000096:biosynthesis; D004352:Drug Resistance, Microbial / Q000502:physiology; D024841:Fluoroquinolones; D016106:Methicillin Resistance / Q000502:physiology; D008826:Microbial Sensitivity Tests; D009675:Novobiocin / Q000494:pharmacology; D015363:Quinolones / Q000378:metabolism / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D059005:Topoisomerase II Inhibitors
chemical_list: D000890:Anti-Infective Agents; D004278:DNA, Superhelical; D024841:Fluoroquinolones; D015363:Quinolones; D059005:Topoisomerase II Inhibitors; D009675:Novobiocin; D002939:Ciprofloxacin; D004250:DNA Topoisomerases, Type II; C061363:sparfloxacin