RecA inactivation as a strategy to reverse the heteroresistance phenomenon in clinical isolates of Escherichia coli

Abstract

RecA inhibition could be an important strategy to combat resistance because of its key role in SOS response, DNA repair and homologous recombination contributing to bacterial survival. This study evaluates the impact of RecA inactivation on heteroresistance in clinical isolates of Escherichia coli and their corresponding recA-deficient isogenic strains to multiple classes of antimicrobial agents. A high frequency (> 30%) of heteroresistance was observed in this collection of clinical isolates. Deletion of the recA gene led to a marked reduction in heteroresistant subpopulations, especially against quinolones or β-lactams. The molecular basis of heteroresistance was associated with increase in copy number of plasmid-borne resistance genes (case of blaTEM-1B) or tandem gene amplifications (case of qnrA1). Of note, in the absence of the recA gene, the increase in copy number of resistance genes was suppressed. This makes the recA gene a promising target for combating heteroresistance.