Lophirones B and C induce oxidative cellular death pathway in Acinetobacter baumannii by inhibiting DNA gyrase

Abstract We evaluated the inactivation of DNA gyrase on the oxidative stress response and sensitivity of A. baumannii to lophirones B and C. The sensitivity of parental and the mutant strains of A. baumannii to lophirones B and C was determined using minimum inhibitory concentration (MIC) and time-kill sensitivity. Inactivation of sodB, katG, recA enhanced the sensitivity of A. baumannii to lophirones B and C. Furthermore, this inactivation increased the accumulation of superoxide anion radical and hydrogen peroxide in lophirones B and C-treated A. baumannii , which was reversed in the presence of thiourea. Inactivation of gyrA stalled lophirones B and C-mediated ROS accumulation in A. baumannii . In addition, lophirones B and C raised the Fe 2+ contents of A. baumannii . Dipyridyl (Fe chelator) reversed the sensitivity of A. baumannii to lophirones B and C. Lophirones significantly lowered the NAD+/NADH ratio of A. baumannii . The results of this study revealed that the impact of DNA gyrase in lophirones B and C-mediated ROS accumulation, Fe 2+ release and cell death.