Conjugal transfer of PMQR from uropathogenic E.coli under high ciprofloxacin selection pressure generates gyrA mutation

Abstract

Incidence of high fluoroquinolone resistance has been rising rapidly worldwide. Resistance against fluoroquinolones can be either chromosomal or plasmid mediated. Plasmid mediated quinolone resistant(PMQR) genes impart low level of resistance against fluoroquinolones but provides favorable background for selection of additional chromosomally encoded resistance mechanisms. In the natural habitat, conjugal transfer of PMQR genes provides a vehicle for dissemination of fluoroquinolone resistance. Our study indicated successful transmission of PMQR determinants(aac(6')-Ib-cr, qnrA, qnrB, qnrS, oqxB) from ciprofloxacin resistant clinical uropathogenic E.coli(UPEC) isolates to susceptible E.coliJ53Azide-resistant strain in vitro in presence of high ciprofloxacin (5 μg/ml) selection pressure generating transconjugants that exhibited varied MIC(25-800μg/ml) towards the drug with acquired mutations Ser83Leu and Asp87Asn in the quinolone resistant determining regions(QRDR) in gyrA. Therefore this is a first study of its kind that identified high rate of gyrA mutations among transconjugants selected under high ciprofloxacin pressure resulting from bacterial conjugation a common phenomenon in natural habitat along with PMQR gene transmission which imposes a major public health concern.

Keywords: Fluoroquinolone resistance; PMQR; QRDR; Uropathogenic E.coli.