Abstract
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.
MeSH terms
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4-Quinolones
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Anti-Infective Agents / pharmacology*
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DNA Gyrase
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DNA Topoisomerases, Type II / genetics
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DNA Topoisomerases, Type II / metabolism
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DNA, Superhelical / chemistry
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DNA, Superhelical / metabolism
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Drug Resistance, Microbial / genetics
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Electrophoresis, Polyacrylamide Gel
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Inhibitory Concentration 50
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Microbial Sensitivity Tests
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Mycobacterium tuberculosis / drug effects*
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Mycobacterium tuberculosis / enzymology*
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Point Mutation / genetics
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / metabolism
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Topoisomerase II Inhibitors*
Substances
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4-Quinolones
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Anti-Infective Agents
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DNA, Superhelical
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Recombinant Proteins
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Topoisomerase II Inhibitors
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DNA Gyrase
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DNA Topoisomerases, Type II