Development of multiple-antibiotic-resistant (Mar) mutants of Pseudomonas aeruginosa after serial exposure to fluoroquinolones

G. G. Zhanel, J. A. Karlowsky, M. H. Saunders, R. J. Davidson, D. J. Hoban, Robert Hancock, I. McLean, L. E. Nicolle

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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 μg/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 coil 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.

Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Issue number2
Publication statusPublished - 1 Jan 1995
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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