Contribution of efflux activity in resistance to antibiotics in Escherichia coli clinical isolates

In an attempt to find new therapeutic strategies for multidrug-resistant infections, understanding the contribution of efflux pumps is of particular importance. This study aimed to determine the contribution of efflux pumps in development of resistance to different classes of antibiotics in clinical isolates of E. coli in order to adopt more effective strategies in the treatment of related infections.

Two methods, i.e. measurement the expression level of some efflux related genes and assessment of efflux activity by H33342 accumulation assay using CCCP as an efflux inhibitor, were applied. The relationship of efflux activity with antibiotic resistance, was evaluated using three criteria including HA (dye accumulation in the absence of CCCP), HAC (dye accumulation in the presence of CCCP) and HAR (HAC/HA).

Expression of tolC in ceftazidime, cefotaxime and azithromycin resistant groups and expression of acrA and mdfA in tetracycline resistant isolates were significantly higher than susceptible ones (p < 0.05). By investigating the simultaneous meeting of three proposed criteria for any studied antibiotics, no significant association was found between efflux activity and antibiotic resistance.

Finding a relation between the overexpression of some efflux genes and resistance to tetracycline, azithromycin and beta-lactams, confirmed the role of these pumps in resistance to mentioned antibiotics and highlighted the neglected role of efflux pumps in resistance to beta-lactams. Meeting two criteria in >70% of investigated antibiotics, confirmed the contribution of efflux as a partial resistance mechanism in these isolates.