Hydrogen sulfide (H₂S) is thought to protect bacteria from oxidative stress, but a comprehensive understanding of its function in bacteria is largely unexplored. In this study, we show that the human pathogen Staphylococcus aureus (S. aureus) harbors significant effector molecules of H₂S signaling, reactive sulfur species (RSS), as low molecular weight persulfides of bacillithiol, coenzyme A, and cysteine, and significant inorganic polysulfide species. We find that proteome S-sulfhydration, a post-translational modification (PTM) in H₂S signaling, is widespread in S. aureus. RSS levels modulate the expression of secreted virulence factors and the cytotoxicity of the secretome, consistent with an S-sulfhydration-dependent inhibition of DNA binding by MgrA, a global virulence regulator. Two previously uncharacterized thioredoxin-like proteins, denoted TrxP and TrxQ, are S-sulfhydrated in sulfide-stressed cells and are capable of reducing protein hydrodisulfides, suggesting that this PTM is potentially regulatory in S. aureus. In conclusion, our results reveal that S. aureus harbors a pool of proteome- and metabolite-derived RSS capable of impacting protein activities and gene regulation and that H₂S signaling can be sensed by global regulators to affect the expression of virulence factors.

中文翻译：

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硫化氢和反应性硫物种影响蛋白质组S-硫酸化和金黄色葡萄球菌的整体毒力调节。

硫化氢（H ₂ S）被认为可以保护细菌免受氧化应激的影响，但对其在细菌中的功能的全面了解尚待探索。在这项研究中，我们表明人类病原体金黄色葡萄球菌（S. aureus）具有H ₂ S信号，反应性硫物种（RSS）的重要效应分子，如低分子量的硫代硫醇，辅酶A和半胱氨酸，以及显着的无机多硫化物种类。我们发现蛋白质组S硫水化，在H ₂ S信号转导中的翻译后修饰（PTM），在金黄色葡萄球菌中很普遍。。RSS水平调节分泌的毒力因子的表达和分泌物组的细胞毒性，这与全球毒力调节剂MgrA对S的硫酸化依赖性DNA结合的抑制作用相一致。在硫化物胁迫的细胞中，两个先前未被表征的硫氧还蛋白样蛋白被称为TrxP和TrxQ，它们被S硫酸化，并能够还原蛋白二硫化氢，表明该PTM在金黄色葡萄球菌中具有潜在的调控作用。总之，我们的结果表明，金黄色葡萄球菌具有蛋白质组和代谢物衍生的RSS，能够影响蛋白质活性和基因调控，并且H ₂S信号可以被全局调节剂感知以影响毒力因子的表达。