Contribution of QnrA, a Plasmid-Mediated Quinolone Resistance Peptide, to Survival of <i>Escherichia coli</i> Exposed to a Lethal Ciprofloxacin Concentration

Abstract

We evaluated the effects of qnrA on survival of bacteria exposed to a lethal ciprofloxacin (CIP) concentration and development of quinolone resistance through the accumulation of amino acid substitutions in quinolone resistance-determining regions (QRDRs) of GyrA and ParC, targets of quinolones, in Escherichia coli. CIP-susceptible E. coli strains of different O-serotypes (O1, O6, O18, O25b, O74, and O78) were transformed by a recombinant plasmid harboring qnrA, and the parent strains and their transformants were subjected to killing curve assays and adaptation tests. In the killing curve assay at 2 × the minimum inhibitory concentration of CIP, the viable bacterial cell numbers of strains O1, O6, and O25b were maintained at 10(5)-10(8) CFU/mL after 24-h incubation, while the remaining strains showed a 10(5)-fold reduction in viable cell numbers. In the adaptation test, a Ser83-Leu substitution in the QRDR of GyrA was identified earlier in the parent strains of O25b and O1 than in their transformants, suggesting that the acquisition of qnrA did not necessarily accelerate the rate of accumulation of amino acid substitutions in the QRDR. We confirmed that the presence of qnrA contributed to increased survival of the E. coli strains displaying certain O-serotypes. Further studies are necessary to evaluate the precise effects of qnrA on quinolone resistance acquisition by Enterobacteriaceae.