title: High-level fluoroquinolone resistance in Pseudomonas aeruginosa due to interplay of the MexAB-OprM efflux pump and the DNA gyrase mutation.
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.
authors.affiliation: Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nakajima
authors.forename: Yohko
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoneyama
authors.forename: Taiji
authors.initials: T
authors.lastname: Nakae
mesh_terms: D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D001426:Bacterial Proteins; D015153:Blotting, Western; D027081:DNA Gyrase / Q000235:genetics / Q000378:metabolism*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D024841:Fluoroquinolones; D015964:Gene Expression Regulation, Bacterial; D026901:Membrane Transport Proteins / Q000378:metabolism*; D016254:Mutagenesis, Insertional; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D024841:Fluoroquinolones; D026901:Membrane Transport Proteins; C423620:MexR protein, Pseudomonas aeruginosa; C402263:OprM protein, Pseudomonas aeruginosa; D012097:Repressor Proteins; D027081:DNA Gyrase