Abstract
We conducted in vitro DNA supercoiling assays, utilizing recombinant DNA gyrases, to elucidate the influence of the lineage-specific serine or threonine residue at position 95 of GyrA on fluoroquinolone resistance in Mycobacterium tuberculosis. There was little effect of the GyrA-Ala74Ser amino acid substitution on activity of the GyrA-Ser95 gyrase, while activity of the GyrA-Asp94Gly-Ser95 gyrase was reduced. These findings were in striking contrast to previous reports analyzing GyrA with Thr95 and suggest an important impact of the amino acid in the development of fluoroquinolone resistance.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Substitution*
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DNA Gyrase / genetics
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DNA Gyrase / metabolism*
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DNA, Bacterial / genetics
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DNA, Superhelical / genetics
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Drug Resistance, Bacterial
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Enzyme Activation
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Escherichia coli / genetics
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Escherichia coli / metabolism
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Fluoroquinolones / pharmacology*
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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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Mycobacterium tuberculosis / genetics
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Plasmids / genetics
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Plasmids / metabolism
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Serine / genetics
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Serine / metabolism
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Threonine / genetics
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Threonine / metabolism
Substances
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DNA, Bacterial
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DNA, Superhelical
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Fluoroquinolones
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Recombinant Proteins
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Threonine
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Serine
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DNA Gyrase