Quinolone resistance in bacteria: emphasis on plasmid-mediated mechanisms.
Bacterial resistance to quinolones/fluoroquinolones has emerged rapidly and such resistance has traditionally been attributed to the chromosomally mediated mechanisms that alter the quinolone targets (i.e. DNA gyrase and topoisomerase IV) and/or overproduce multidrug resistance efflux pumps. However, the discovery of the plasmid-borne quinolone resistance determinant, named qnr, has substantially broadened our horizon on the molecular mechanisms of quinolone resistance. Several recent reports of Qnr or its homologues encoded by transferable plasmids in Gram-negative bacteria isolated worldwide highlight the significance of the emerging plasmid-mediated mechanism(s). This also alerts us to the potential rapid dissemination of quinolone resistance determinants. Qnr belongs to the pentapeptide repeat family and protects DNA gyrase from the action of quinolone agents including the newer fluoroquinolones. This protection interplays with chromosomal mechanisms to raise significantly the resistance levels. The qnr-bearing strains generate quinolone-resistant mutants at a much higher frequency than those qnr-free strains. Furthermore, the qnr-plasmids are integron-associated and carry multiple resistance determinants providing resistance to several classes of antimicrobials including beta-lactams and aminoglycosides. The high quinolone resistance rates in Escherichia coli are used to address issues of quinolone resistance, and possible strategies for minimising quinolone resistance are discussed.
Li
Xian-Zhi
XZ
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3202, USA. xianzhi_li@hc-sc.gc.ca
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects; D029968:Escherichia coli Proteins / Q000502:physiology; D032023:Integrons; D010957:Plasmids; D015363:Quinolones / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; C485384:Qnr protein, E coli; D015363:Quinolones