The Role of AcrAB-TolC Efflux Pump in Mediating Fluoroquinolone Resistance in Naturally Occurring Salmonella Isolates from China.

The involvement of AcrAB-TolC efflux pump in regulating fluoroquinolone resistance of naturally occurring Salmonella isolates is insufficiently investigated. In this study, the regulatory genes, acrR, ramR, marRAB, and soxRS of AcrAB-TolC efflux pump, of 27 naturally occurring fluoroquinolone-resistant Salmonella isolates collected in China were sequenced. The expression levels of acrB, ramA, marA, and soxS were also examined using quantitative real-time polymerase chain reaction. Gene alterations were mainly observed for acrR (three mutation types) and ramR (four mutation types), not for marRAB (no mutation) or soxRS (one mutaton type). Overexpressions were also mainly observed for acrB and ramA, not for marA or soxS. Some mutations/deletions in ramR caused highly elevated expression of ramA. Complementation with wild-type ramR gene reduced mRNA levels of acrB and ramA by 1.7- to 2.2-fold and 10.5- to 30.1-fold, respectively, and lowered fluoroquinolones (FQ) minimum inhibitory concentrations by 2- to 8-fold. Neither MarA nor SoxS was found to be associated with increased FQ resistance. This study shows that the AcrAB efflux pump is playing a role in mediating fluoroquinolone resistance, and RamA may be the major global regulator of AcrAB-TolC-mediated fluoroquinolone resistance in Salmonella.