Ineffectiveness of topoisomerase mutations in mediating clinically significant fluoroquinolone resistance in Escherichia coli in the absence of the AcrAB efflux pump

Fluoroquinolone-resistant mutants, selected from a wild-type Escherichia co li K-12 strain and its Mar mutant by exposure to increasing levels of oflox acin on solid medium, were analyzed by Northern (RNA) blot analysis, sequen cing, and radiolabelled ciprofloxacin accumulation studies. Mutations in th e target gene gyrA (DNA gyrase), the regulatory gene marR, and additional, as yet unidentified genes (genes that probably affect efflux mediated by th e multidrug efflux pump AcrAB) all contributed to fluoroquinolone resistanc e. Inactivation of the acrAB locus made all strains, including those with t arget gene mutations, hypersusceptible to fluoroquinolones and certain othe r unrelated drugs. These studies indicate that, in the absence of the AcrAB pump, gyrase mutations fail to produce clinically relevant levels of fluor oquinolone resistance.