Mutations in GyrA, ParC, MexR and NfxB in clinical isolates of Pseudomonas aeruginosa.
The target enzymes GyrA and ParC and two efflux pump regulatory genes mexR and nfxB were analysed to determine changes associated with fluoroquinolone resistance in Pseudomonas aeruginosa. Both low- and high-level ciprofloxacin resistance was associated with a Thr-83Ile substitution in GyrA. A ParC Ser-80Leu substitution was found in highly resistant isolates in tandem with the Thr-83Ile substitution in GyrA. Mutations in the efflux regulatory genes were associated with resistance only when in tandem with a mutation in GyrA or ParC. These data show that the main mechanism of fluoroquinolone resistance in P. aeruginosa is mediated primarily through mutations in GyrA, and that mutations in ParC and the efflux regulatory genes are secondary.
Institute of Medical Microbiology, Immunology and Hygiene, University of Cologne, Goldenfelstrasse 19-21, 50935 Cologne, Germany. paul.higgins@medizin.uni-koeln.de
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PG
Higgins
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Fluit
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Milatovic
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J
Verhoef
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FJ
Schmitz
D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics*; D002939:Ciprofloxacin / Q000494:pharmacology; D027081:DNA Gyrase / Q000737:chemistry / Q000235:genetics*; D027101:DNA Topoisomerase IV / Q000737:chemistry / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics*; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*
D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C423620:MexR protein, Pseudomonas aeruginosa; C077901:NfxB protein, Pseudomonas aeruginosa; D012097:Repressor Proteins; D014157:Transcription Factors; D002939:Ciprofloxacin; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase