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

• Published in: Microbial pathogenesis 2019-05, Vol.130, p.226-231
• Main Authors: Ajiboye, T.O., Aliyu, N.O., Ajala-Lawal, R.A.
• Format: Article
• Language: English
• Subjects: Acinetobacter baumannii; DNA gyrase A; Fenton chemistry; Hydroxyl radical; Lophirones B and C; Oxidative DNA damage
• ISSN: 0882-4010; 1096-1208
• DOI: 10.1016/j.micpath.2019.03.011

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 Fe2+ 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, Fe2+ release and cell death. [Display omitted] •Inactivation of sodB, katG and recA increases susceptibility of Acinetobacter baumannii to lophirones B and C.•Lophirones B and C induced reactive oxygen species accumulation in Acinetobacter baumannii.•The inhibition of gyrA contributes to the accumulation of reactive oxygen species.•Lophirones B and C inhibited NADH dehydrogenase complex electron transport chain activity of Acinetobacter baumannii.