Abstract
Fluoroquinolone resistance in Pseudomonas aeruginosa is mainly attributable to the constitutive expression of the xenobiotic efflux pump and mutation in DNA gyrase or topoisomerase IV. We constructed cells with a double-mutation in gyrA and mexR encoding DNA gyrase and repressor for the mexAB-oprM operon, respectively. The mutant showed 1,024 times higher fluoroquinolone resistance than cells lacking the MexAB-OprM. Cells with a single mutation in gyrA and producing a wild-type level of the MexAB-OprM efflux pump showed 128 times higher fluoroquinolone resistance than cells lacking the MexAB-OprM. In contrast, a single mutation in gyrA or mexR caused only 4 and 64 times higher resistance, respectively. These findings manifested the interplay between the MexAB-OprM efflux pump and the target mutation in fluoroquinolone resistance.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Infective Agents / pharmacokinetics
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Anti-Infective Agents / pharmacology*
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Bacterial Outer Membrane Proteins / metabolism*
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Bacterial Proteins*
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Blotting, Western
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DNA Gyrase / genetics
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DNA Gyrase / metabolism*
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Drug Resistance, Bacterial / genetics*
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Fluoroquinolones
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Gene Expression Regulation, Bacterial
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Membrane Transport Proteins / metabolism*
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Mutagenesis, Insertional
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Pseudomonas aeruginosa / drug effects
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Pseudomonas aeruginosa / genetics
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Pseudomonas aeruginosa / metabolism*
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
Substances
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Anti-Infective Agents
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Bacterial Outer Membrane Proteins
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Bacterial Proteins
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Fluoroquinolones
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Membrane Transport Proteins
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MexR protein, Pseudomonas aeruginosa
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OprM protein, Pseudomonas aeruginosa
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Repressor Proteins
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DNA Gyrase