In-vitro mutagenesis of qnrA and qnrS genes and quinolone resistance in Escherichia coli

Plasmid-mediated quinolone resistance is being reported increasingly worldwide among isolates of enterobacteria. This resistance is mostly associated with Qnr-like determinants that confer resistance to quinolones, e.g., nalidixic acid, and reduced susceptibility to fluoroquinolones. This study investigated whether amino-acid substitutions in QnrA1 and QnrS1 determinants might be responsible for an enhancement of resistance to quinolones and, particularly, to fluoroquinolones. However, random and site-directed mutagenesis failed to identify any single amino-acid substitution that could be responsible for higher levels of resistance to quinolones or fluoroquinolones, indicating that the selection of such mutants in vivo is probably a rare event.