Antioxidants, Redox Biology and Toxicology Research Laboratory, Department of Medical Biochemistry, Nile University of Nigeria, FCT-Abuja, Nigeria; Project Group P2, Robert Koch Institute, Wernigerode Branch, Germany.
Project Group P2, Robert Koch Institute, Wernigerode Branch, Germany.
Microb Pathog. 2018 Jun;119:35-41. doi: 10.1016/j.micpath.2018.03.060. Epub 2018 Mar 31.
Ferric uptake regulator (Fur) is important in the regulation of bacterial iron metabolism and uptake of Fe from the environment. We evaluated the contribution of fur to the sensitivity and oxidative response of A. baumannii to antibiotics. Deletion of fur increased the sensitivity of A. baumannii AB5075 to colistin, gentamicin, rifampicin and tigecycline. Furthermore, activities of superoxide dismutase and catalase in Δfur mutant decreased significantly compared to the parental strain. Conversely, •O- and HO accumulate in colistin, gentamicin, rifampicin or tigecycline-treated Δfur mutant compared to the parental strain. Ferrous ion (Fe) content of Δfur mutant increased compared to the parental strain. Fe chelator 2,2'-bipyridyl lowered the sensitivity of A. baumannii to the antibiotics. The antibiotics, except tigecycline, raised the NAD+/NADH and ADP/ATP ratio of Δfur mutant compared to the WT. Glutathione content of Δfur mutant was significantly depleted compared to parental strain following exposure to the antibiotics. We conclude that decreased capability of Δfur mutant to detoxify reactive oxygen species raised its susceptibility to antibiotics through Fenton chemistry.
铁摄取调节剂 (Fur) 在细菌铁代谢和从环境中摄取铁的调节中很重要。我们评估了 fur 对鲍曼不动杆菌对抗生素的敏感性和氧化反应的贡献。fur 的缺失增加了 AB5075 对黏菌素、庆大霉素、利福平利福平和替加环素的敏感性。此外，与亲本菌株相比，Δfur 突变体中超氧化物歧化酶和过氧化氢酶的活性显著降低。相反，与亲本菌株相比，在黏菌素、庆大霉素、利福平或替加环素处理的 Δfur 突变体中，•O-和 HO 积累。与亲本菌株相比，Δfur 突变体中的亚铁离子 (Fe) 含量增加。铁螯合剂 2,2'-联吡啶降低了鲍曼不动杆菌对抗生素的敏感性。除替加环素外，与 WT 相比，抗生素使 Δfur 突变体中的 NAD+/NADH 和 ADP/ATP 比值升高。与亲本菌株相比，暴露于抗生素后，Δfur 突变体中的谷胱甘肽含量明显耗尽。我们得出的结论是，Δfur 突变体降低了清除活性氧的能力，通过 Fenton 化学提高了其对抗生素的敏感性。
