Manganese impairs the QoxABCD terminal oxidase leading to respiration-associated toxicity,Molecular Microbiology

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Manganese impairs the QoxABCD terminal oxidase leading to respiration-associated toxicity
Molecular Microbiology ( IF 2.6 ) Pub Date : 2021-06-07 , DOI: 10.1111/mmi.14767
Ankita J Sachla ₁ , Yuanchan Luo _{1,

2} , John D Helmann ₁

Affiliation

Cell physiology relies on metalloenzymes and can be easily disrupted by imbalances in metal ion pools. Bacillus subtilis requires manganese for growth and has highly regulated mechanisms for import and efflux that help maintain homeostasis. Cells defective for manganese (Mn) efflux are highly sensitive to intoxication, but the processes impaired by Mn excess are often unknown. Here, we employed a forward genetics approach to identify pathways affected by manganese intoxication. Our results highlight a central role for the membrane-localized electron transport chain in metal intoxication during aerobic growth. In the presence of elevated manganese, there is an increased generation of reactive radical species associated with dysfunction of the major terminal oxidase, the cytochrome aa₃ heme-copper menaquinol oxidase (QoxABCD). Intoxication is suppressed by diversion of menaquinol to alternative oxidases or by a mutation affecting heme A synthesis that is known to convert QoxABCD from an aa₃ to a bo₃-type oxidase. Manganese sensitivity is also reduced by derepression of the MhqR regulon, which protects cells against reactive quinones. These results suggest that dysfunction of the cytochrome aa₃-type quinol oxidase contributes to metal-induced intoxication.

中文翻译：

锰会损害 QoxABCD 末端氧化酶，导致呼吸相关毒性

细胞生理学依赖于金属酶，并且很容易被金属离子池中的不平衡所破坏。枯草芽孢杆菌的生长需要锰，并且具有高度调节的输入和流出机制，有助于维持体内平衡。锰 (Mn) 流出缺陷的细胞对中毒高度敏感，但锰过量损害的过程通常是未知的。在这里，我们采用前向遗传学方法来识别受锰中毒影响的途径。我们的研究结果强调了膜局部电子传递链在有氧生长过程中金属中毒中的核心作用。在锰含量升高的情况下，与主要末端氧化酶（细胞色素aa _{3 ）功能障碍相关的活性自由基种类增加}血红素铜甲基萘醌氧化酶 (QoxABCD)。通过甲基萘醌转向替代氧化酶或通过影响血红素A合成的突变抑制中毒，已知该突变将QoxABCD从aa ₃型氧化酶转化为bo ₃型氧化酶。MhqR regulon 的去抑制也会降低锰的敏感性，MhqR regulon 可以保护细胞免受反应性醌的侵害。这些结果表明，细胞色素aa ₃型喹啉氧化酶的功能障碍有助于金属诱导的中毒。

更新日期：2021-06-07

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