title: Development of multiple-antibiotic-resistant (Mar) mutants of Pseudomonas aeruginosa after serial exposure to fluoroquinolones.
abstract: Laboratory-derived fluoroquinolone-resistant mutants were created by serially passaging wild-type Pseudomonas aeruginosa on fluoroquinolone-containing agar to obtain high-level fluoroquinolone resistance (e.g., ciprofloxacin MIC of 1,024 micrograms/ml). With increases of 4- to 32-fold in MICs of fluoroquinolones, these organisms demonstrated (relative to wild-type) normal morphology, resistance to fluoroquinolones only, no change in fluoroquinolone uptake, and no change in lipopolysaccharide profiles or outer membrane protein profiles. Complementation with wild-type Escherichia coli gyrA restored fluoroquinolone susceptibility, suggesting that these were gyrA mutants. After 4- to 32-fold increases in fluoroquinolone MICs (with continued passage on fluoroquinolone-containing agar) isolates demonstrated altered morphology, a multiple-antibiotic-resistant (Mar) phenotype (including cross-resistance to beta-lactams, chloramphenicol, and tetracycline), reduced fluoroquinolone uptake and altered outer membrane proteins (reductions in the 25- and 38-kDa bands as well as several bands in the 43- to 66-kDa region). Complementation with wild-type E. coli gyrA partially reduced the level of fluoroquinolone resistance by approximately 8- to 32-fold, suggesting that these mutants displayed both gyrA and non-gyrA mutations.
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
authors.forename: G G
authors.initials: GG
authors.lastname: Zhanel
authors.forename: J A
authors.initials: JA
authors.lastname: Karlowsky
authors.forename: M H
authors.initials: MH
authors.lastname: Saunders
authors.forename: R J
authors.initials: RJ
authors.lastname: Davidson
authors.forename: D J
authors.initials: DJ
authors.lastname: Hoban
authors.forename: R E
authors.initials: RE
authors.lastname: Hancock
authors.forename: I
authors.initials: I
authors.lastname: McLean
authors.forename: L E
authors.initials: LE
authors.lastname: Nicolle
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000032:analysis; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D004926:Escherichia coli / Q000201:enzymology; D008826:Microbial Sensitivity Tests; D015366:Pefloxacin / Q000493:pharmacokinetics; D018272:Porins / Q000032:analysis; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000890:Anti-Infective Agents; D001425:Bacterial Outer Membrane Proteins; D018272:Porins; D015366:Pefloxacin; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II