OBJECTIVES: Garenoxacin, a des-fluoro(6)-quinolone, exhibits potent activity against Mycoplasma pneumoniae, including macrolide-resistant strains. There has been no report on the inhibitory activity of garenoxacin against the target enzyme of M. pneumoniae. METHODS: Subunits of DNA gyrase (GyrA and GyrB) proteins of M. pneumoniae FH were separately expressed as His-tagged proteins in Escherichia coli Chaperone Competent Cell BL21 by IPTG induction of plasmids containing the respective gyrA and gyrB genes. The inhibitory activities of garenoxacin, moxifloxacin, gatifloxacin and levofloxacin against DNA gyrase were evaluated by the inhibition of supercoiling activity (n = 3). RESULTS: Against M. pneumoniae FH, garenoxacin showed 2- to 16-fold more potent activity than the other quinolones. The mean IC(50) of garenoxacin for DNA gyrase of M. pneumoniae was 2.5 mg/L. Garenoxacin showed the most potent inhibitory activity against M. pneumoniae DNA gyrase among the quinolones tested. The IC(50) values of the quinolones for DNA gyrase roughly correlated with each MIC value. CONCLUSIONS: The antimycoplasmal activity of the quinolones was almost certainly due to inhibition of the supercoiling activity of DNA gyrase. Garenoxacin was considered a valuable quinolone in the treatment of infectious diseases caused by M. pneumoniae.
OBJECTIVES:Garenoxacin, a des-fluoro(6)-quinolone, exhibits potent activity against Mycoplasma pneumoniae, including macrolide-resistant strains. There has been no report on the inhibitory activity of garenoxacin against the target enzyme of M. pneumoniae. METHODS: Subunits of DNA gyrase (GyrA and GyrB) proteins of M. pneumoniae FH were separately expressed as His-tagged proteins in Escherichia coli Chaperone Competent Cell BL21 by IPTG induction of plasmids containing the respective gyrA and gyrB genes. The inhibitory activities of garenoxacin, moxifloxacin, gatifloxacin and levofloxacin against DNA gyrase were evaluated by the inhibition of supercoiling activity (n = 3). RESULTS: Against M. pneumoniae FH, garenoxacin showed 2- to 16-fold more potent activity than the other quinolones. The mean IC(50) of garenoxacin for DNA gyrase of M. pneumoniae was 2.5 mg/L. Garenoxacin showed the most potent inhibitory activity against M. pneumoniae DNA gyrase among the quinolones tested. The IC(50) values of the quinolones for DNA gyrase roughly correlated with each MIC value. CONCLUSIONS: The antimycoplasmal activity of the quinolones was almost certainly due to inhibition of the supercoiling activity of DNA gyrase. Garenoxacin was considered a valuable quinolone in the treatment of infectious diseases caused by M. pneumoniae.