Aix-Marseille University, CNRS, Laboratoire de Chimie Bactérienne, Institut de Microbiologie de la Méditerranée, 13402 Marseille, France.
Institut de Microbiologie de la Méditerranée, Plate-forme Transcriptomique, 13402 Marseille, France.
Proc Natl Acad Sci U S A. 2023 Apr 4;120(14):e2215997120. doi: 10.1073/pnas.2215997120. Epub 2023 Mar 28.
The cell envelope of gram-negative bacteria constitutes the first protective barrier between a cell and its environment. During host infection, the bacterial envelope is subjected to several stresses, including those induced by reactive oxygen species (ROS) and reactive chlorine species (RCS) produced by immune cells. Among RCS, chlorotaurine (ChT), which results from the reaction between hypochlorous acid and taurine, is a powerful and less diffusible oxidant. Here, using a genetic approach, we demonstrate that Typhimurium uses the CpxRA two-component system to detect -ChT oxidative stress. Moreover, we show that periplasmic methionine sulfoxide reductase (MsrP) is part of the Cpx regulon. Our findings demonstrate that MsrP is required to cope with -ChT stress by repairing -ChT-oxidized proteins in the bacterial envelope. By characterizing the molecular signal that induces Cpx when Typhimurium is exposed to -ChT, we show that -ChT triggers Cpx in an NlpE-dependent manner. Thus, our work establishes a direct link between -ChT oxidative stress and the envelope stress response.
革兰氏阴性菌的细胞包膜构成了细胞与其环境之间的第一道保护屏障。在宿主感染过程中，细菌包膜会受到多种应激的影响，包括免疫细胞产生的活性氧（ROS）和活性氯（RCS）的影响。在 RCS 中，由次氯酸和牛磺酸反应生成的氯代牛磺酸（ChT）是一种强大且不易扩散的氧化剂。在这里，我们通过遗传方法证明，鼠伤寒沙门氏菌利用 CpxRA 双组分系统来检测 -ChT 氧化应激。此外，我们还表明，周质甲硫氨酸亚砜还原酶（MsrP）是 Cpx 调控子的一部分。我们的研究结果表明，MsrP 通过修复细菌包膜中 -ChT 氧化的蛋白质来应对 -ChT 应激。通过描述当鼠伤寒沙门氏菌暴露于 -ChT 时诱导 Cpx 的分子信号，我们表明 -ChT 以 NlpE 依赖性方式触发 Cpx。因此，我们的工作建立了 -ChT 氧化应激与包膜应激反应之间的直接联系。
