文章基本信息

标题：The cytochrome bd-type quinol oxidase is important for survival of Mycobacterium smegmatis under peroxide and antibiotic-induced stress
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作者：Ping Lu ; Marieke H. Heineke ; Anil Koul 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2015
卷号：5
DOI：10.1038/srep10333
出版社：Springer Nature
摘要：Targeting respiration and ATP synthesis has received strong interest as a new strategy for combatting drug-resistant Mycobacterium tuberculosis . Mycobacteria employ a respiratory chain terminating with two branches. One of the branches includes a cytochrome bc ₁ complex and an aa ₃-type cytochrome c oxidase while the other branch terminates with a cytochrome bd -type quinol oxidase. In this communication we show that genetic inactivation of cytochrome bd , but not of cytochrome bc ₁, enhances the susceptibility of Mycobacterium smegmatis to hydrogen peroxide and antibiotic-induced stress. The type-II NADH dehydrogenase effector clofazimine and the ATP synthase inhibitor bedaquiline were bacteriostatic against wild-type M. smegmatis , but strongly bactericidal against a cytochrome bd mutant. We also demonstrated that the quinone-analog aurachin D inhibited mycobacterial cytochrome bd at sub-micromolar concentrations. Our results identify cytochrome bd as a key survival factor in M. smegmatis during antibiotic stress. Targeting the cytochrome bd respiratory branch therefore appears to be a promising strategy that may enhance the bactericidal activity of existing tuberculosis drugs.