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Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1995 Feb;39(2):489–495. doi: 10.1128/aac.39.2.489

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

G G Zhanel 1, J A Karlowsky 1, M H Saunders 1, R J Davidson 1, D J Hoban 1, R E Hancock 1, I McLean 1, L E Nicolle 1
PMCID: PMC162565  PMID: 7726519

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.

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Selected References

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