HprSR Is a Reactive Chlorine Species-Sensing, Two-Component System in Escherichia coli
HprSR Is a Reactive Chlorine Species-Sensing, Two-Component System in Escherichia coli
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DOI：
10.1128/jb.00449-21
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发表时间：
2022-02-01
影响因子：
3.2
通讯作者：
Ezraty, Benjamin
中科院分区：
文献类型：
--
作者：
El Hajj, Sara;Henry, Camille;Ezraty, Benjamin
双组分系统（TCS）是允许细菌细胞感知、响应和适应波动环境的信号通路。在大肠杆菌的经典TCS中，HprSR最近被证明参与msrPQ的调节，msrPQ编码周质甲硫氨酸亚砜还原酶系统。在这项研究中，我们证明，次氯酸（HOCl）诱导的表达msrPQ的HprSR依赖的方式，而过氧化氢，NO和百草枯（超氧化物发生器）不。因此，HprS似乎是一种HOCI敏感的组胺酸激酶。使用定向诱变方法，我们表明位于HprS周质环中的Met残基对其活性很重要：我们提供的证据表明，由于HOCl优先氧化Met残基，HprS可以通过其甲硫氨酸残基的可逆氧化来激活，这意味着MsrPQ在关闭HprSR中起作用。我们建议，HprS的活化HOCl可以发生通过Met氧化还原开关。HprSR似乎是第一个能够检测E.杆菌这项研究是理解原核生物RCS抗性机制的重要一步。重要性了解细菌如何在分子水平上对氧化应激作出反应，在对抗病原体方面至关重要。HOCl是最有效的工业和生理杀微生物氧化剂之一。因此，细菌已经开发出对抗策略以在HOCl诱导的应激中存活。在过去的十年中，已经获得了对这些细菌保护因子的重要见解。我们的工作建立了HprSR作为一个反应性氯物种传感，双组分系统在大肠杆菌MG 1655，它调节msrPQ，两个基因编码，HOCl氧化蛋白的修复系统的表达。此外，我们提供的证据表明，HOCl可以激活HprS通过蛋氨酸氧化还原开关。
Two-component systems (TCS) are signaling pathways that allow bacterial cells to sense, respond to, and adapt to fluctuating environments. Among the classical TCS of Escherichia coif, HprSR has recently been shown to be involved in the regulation of msrPQ, which encodes the periplasmic methionine sulfoxide reductase system. In this study, we demonstrated that hypochlorous acid (HOCl) induces the expression of msrPQ in an HprSR-dependent manner, whereas H2O2, NO, and paraquat (a superoxide generator) do not. Therefore, HprS appears to be an HOCI-sensing histidine kinase. Using a directed mutagenesis approach, we showed that Met residues located in the periplasmic loop of HprS are important for its activity: we provide evidence that as HOCl preferentially oxidizes Met residues, HprS could be activated via the reversible oxidation of its methionine residues, meaning that MsrPQ plays a role in switching HprSR off. We propose that the activation of HprS by HOCl could occur through a Met redox switch. HprSR appears to be the first characterized KS able to detect reactive chlorine species (RCS) in E. coli. This study represents an important step toward understanding the mechanisms of RCS resistance in prokaryotes.IMPORTANCE Understanding how bacteria respond to oxidative stress at the molecular level is crucial in the fight against pathogens. HOCl is one of the most potent industrial and physiological microbicidal oxidants. Therefore, bacteria have developed counterstrategies to survive HOCl-induced stress. Over the last decade, important insights into these bacterial protection factors have been obtained. Our work establishes HprSR as a reactive chlorine species-sensing, two-component system in Escherichia coli MG1655, which regulates the expression of msrPQ, two genes encoding, a repair system for HOCl-oxidized proteins. Moreover, we provide evidence suggesting that HOCl could activate HprS through a methionine redox switch.