Synergistic quinolone sensitization by targeting recA SOS response gene and oxidative stress [Mechanisms of Action]

xloma.fota13 shared this article with you from Inoreader Synergistic quinolone sensitization by targeting recA SOS response gene and oxidative stress [Mechanisms of Action] Via AAC Accepts: Articles Published Ahead of Print Suppression of recA SOS response gene and reactive oxygen species (ROS) overproduction have been shown, separately, to enhance fluoroquinolone activity and lethality. Their putative synergistic impact as a strategy to potentiate the efficacy of bactericidal antimicrobial agents like fluoroquinolones is unknown. We generated Escherichia coli mutants that exhibited suppressed recA gene in combination with inactivated ROS detoxification system genes (sodA, sodB, katG, katE, ahpC) or inactivated oxidative stress regulator genes (oxyR, rpoS) to evaluate the interplay of both DNA repair and detoxification systems in drug response. Synergistic sensitization effects, ranging from 7.5- to 30-fold relative to the wild-type, were observed with ciprofloxacin in double knockouts of recA and inactivated detoxification system genes. Compared to recA knockout, inactivation of an additional detoxification system gene reduced MIC values up to 8-fold. In growth curves, no growth was evident in mutants doubly-deficient for recA gene and oxidative detoxification systems at subinhibitory concentrations of ciprofloxacin, in contrast to the recA-deficient strain. There was a marked reduction of viable bacteria in a short period of time when recA gene and other detoxification system genes (katG, sodA or ahpC) were inactivated (using absolute ciprofloxacin concentrations). At 4 hours, a bactericidal e ffect of ciprofloxacin was observed for katG/recA and ahpC/recA double mutants compared to the single recA mutant (3.4 Log10 CFU/mL). Synergistic quinolone sensitization, by targeting the recA gene and oxidative detoxification stress systems, reinforces the role of both DNA repair systems and ROS in antibiotic-induced bacterial cell death, opening up a new pathway for antimicrobial sensitization. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.