Inhibitory activity of quinolones against DNA gyrase of Mycobacterium tuberculosis.
The in vitro inhibitory activities of quinolones against Mycobacterium tuberculosis DNA gyrase were measured. The 50% inhibitory concentrations (IC(50)s) of sitafloxacin (DU-6859a), sparfloxacin, ciprofloxacin and levofloxacin against supercoiling activity of DNA gyrase were 1.67, 4.80, 12.2 and 13.9 mg/L, respectively, and correlated well with their MICs. Two altered proteins of GyrA containing Ala-90Val, or Ala-90Val and Asp-94Gly were also purified and the inhibitory activities of the quinolones ranged from 12 to >83 times weaker than those against the wild-type enzyme. These results suggest that mutations in the corresponding genes confer quinolone resistance.
Onodera
Y
Y
New Product Research Laboratories I, Daiichi Pharmaceutical Co. Ltd, 16-13 Kitakasai 1-chome, Edogawa-ku, Tokyo 134-8630, Japan. onode90j@daiichipharm.co.jp
Tanaka
M
M
Sato
K
K
D042462:4-Quinolones; D000890:Anti-Infective Agents / Q000494:pharmacology*; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism; D004278:DNA, Superhelical / Q000737:chemistry / Q000378:metabolism; D004352:Drug Resistance, Microbial / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology*; D017354:Point Mutation / Q000235:genetics; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D059005:Topoisomerase II Inhibitors
D042462:4-Quinolones; D000890:Anti-Infective Agents; D004278:DNA, Superhelical; D011994:Recombinant Proteins; D059005:Topoisomerase II Inhibitors; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II