title: In vitro antichlamydial activity of garenoxacin against Chlamydia trachomatis.
abstract: Garenoxacin showed the most potent chlamydial activity against Chlamydia trachomatis D/UW-3/Cx among three tested quinolones and azithromycin. The DNA gyrase genes, gyrA and gyrB, of C. trachomatis D/UW-3/Cx were cloned and the GyrA and GyrB subunits of DNA gyrase protein were separately expressed as histidine-tagged proteins in Escherichia coli. The mean 50% inhibitory concentration (IC(50)) of garenoxacin against the supercoiling activity of C. trachomatis D/UW-3/Cx gyrase was 2.9 ± 0.4 μg/ml, which was the most potent inhibitory activity against DNA gyrase among the quinolones tested in this study. At an extracellular concentration of 0.5 μg/ml, the cellular-to-extracellular concentration ratio of garenoxacin was 15.3 ± 1.3, equivalent to that of moxifloxacin and greater than that of levofloxacin. In a time-kill experiment, after exposure to garenoxacin at a concentration of 0.5 μg/ml at 0-6, 5-11, and 24-30 h after infection, the percentages of recoverable chlamydial inclusion-forming units were 11.1 ± 3.3, 0.6 ± 0.1, and 2.6 ± 0.5%, respectively. On transmission electron microscopy observation, after exposure to garenoxacin at 24-30 h after infection, some C. trachomatis elementary bodies remained in the inclusion body; however, the reticulate bodies were completely disrupted. In conclusion, garenoxacin is expected to be a useful quinolone in the treatment of infectious diseases caused by C. trachomatis.
authors: Research Laboratories, Toyama Chemical Co., Ltd, 2-4-1 Shimookui, Toyama, 930-8508, Japan. naoko_futakuchi@toyama-chemical.co.jp
authors: Naoko
authors: N
authors: Futakuchi
authors: Masatoshi
authors: M
authors: Nakatani
authors: Masahiro
authors: M
authors: Takahata
authors: Junichi
authors: J
authors: Mitsuyama
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002692:Chlamydia trachomatis / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D027081:DNA Gyrase / Q000235:genetics / Q000378:metabolism; D057075:Enzyme Assays; D024841:Fluoroquinolones / Q000493:pharmacokinetics / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D046529:Microscopy, Electron, Transmission; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D024841:Fluoroquinolones; D011994:Recombinant Proteins; D027081:DNA Gyrase; C419689:garenoxacin