Expression of AcrAB Efflux Pump and Role of Mefloquine as Efflux Pump Inhibitor in MDR E.coli

Abstract

Multi-drug resistant Escherichia coli (MDRE. coli), represents a major health problem. The AcrAB pump constitutes a major drug efflux system. Inhibition of efflux pumps is an approach to combat the drug resistance problem. Mefloquine is a bacterial RND efflux-pump inhibitor (EPI). This study aimed to investigate the expression levels of multidrug efflux genes acrAB, as well, to study the effect of mefloquine as an efflux pump inhibitor. acrA and acrB gene expression was measured using real-time PCR. Effect of mefloquine hydrochloride on minimum inhibitory concentration (MIC) of selected antibiotics against the tested isolates was determined using the broth microdilution technique. Overexpression of both genes was detected in all isolates. The differences between expression levels of both genes in MDR strains and an ATCC reference strain were statistically significant (p ˂ 0.001). There was a moderate correlation between acrA and acrB genes expression levels. (r = 0.593, p < 0.001). The isolates showed a decrease in MIC in presence of EPI. Susceptibility to levofloxacin was recovered in 95% of the tested isolates, 62.5% to ceftriaxone and in 5% each to ciprofloxacin and Gentamicin. In conclusion, Inhibition of acrAB efflux pump in MDR E. coli by mefloquine could be considered in the design of future antibiotics.