title: Ofloxacin-resistant Pseudomonas aeruginosa mutants with elevated drug extrusion across the inner membrane.
abstract: We selected the quinolone-resistant mutants from the protein F deficient Pseudomonas aeruginosa. The mutants showed cross-resistance to tetracycline, minocycline and chloramphenicol, but not to the beta-lactam antibiotics. The MIC of ofloxacin (OFLX) against the mutants, but not in the parent, became 2 to 4 times lower as the medium pH was raised from 6.5 to 8.5. The mutants accumulated about half as much OFLX as the parent. The OFLX accumulation in the mutants increased 6.5- to 8-fold in the presence of 100 mM carbonyl cyanide m-chlorophenylhydrazone, while that in the parent was 4-fold. The OFLX sensitivity of the mutant DNA-gyrase was comparable with that of the parent's enzyme. These results suggest that the resistance of these mutants to OFLX is associated with the membrane potential dependent drug efflux.
authors.affiliation: Department of Cellular Information Sciences, Tokai University, School of Medicine, Isehara, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Lei
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Nakae
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003470:Culture Media; D004250:DNA Topoisomerases, Type II / Q000302:isolation & purification / Q000378:metabolism*; D004352:Drug Resistance, Microbial / Q000235:genetics*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D016296:Mutagenesis; D015242:Ofloxacin / Q000378:metabolism / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D003470:Culture Media; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D015242:Ofloxacin; D004250:DNA Topoisomerases, Type II