Exploring the Interplay of Resistance Nodulation Division Efflux Pumps, AmpC and OprD in Antimicrobial Resistance of Burkholderia cepacia Complex in Clinical Isolates.

Aim: This study aimed at investigating the association of gene expression of multidrug efflux pumps (MexA, MexC, MexE, and MexX), the outer membrane porin OprD, and the ß-lactamase AmpC with the antimicrobial susceptibility among 44 clinical isolates of Burkholderia cepacia complex (Bcc). Results: Increased expression of ampC gene showed significant association with reduced susceptibility to chloramphenicol. In fact, reduced susceptibility to chloramphenicol was correlated with overexpression of most genes (ampC, mexC, mexE, and mexX) studied here in majority (>95%) of the Bcc isolates. Increased mexA expression showed significant association with reduced susceptibility to ß-lactam antimicrobials (ceftazidime, piperacillin-tazobactam, and meropenem) and co-trimoxazole. Reduced susceptibility to meropenem also showed significant correlation with overexpression of mexC and mexX, whereas reduced susceptibility to ceftazidime was also associated with mexE overexpression. Reduced susceptibility to levofloxacin was significantly associated with overexpression of mexX. The involvement of the efflux pumps in levofloxacin and ceftazidime resistance was further inferred from the finding that the efflux pump inhibitor, carbonyl cyanide m-chlorophenylhydrazone reduced minimum inhibitory concentrations for both the antimicrobials. Conclusions: To conclude, this study explored the high-level expression of mexC, mexE, and mexX efflux pumps genes and ampC in the clinical isolates of Bcc, which can be targeted at treating infections caused by Bcc.