The novel protein ScrA acts through the SaeRS two-component system to regulate virulence gene expression in Staphylococcus aureus,Molecular Microbiology

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The novel protein ScrA acts through the SaeRS two-component system to regulate virulence gene expression in Staphylococcus aureus
Molecular Microbiology ( IF 2.6 ) Pub Date : 2022-04-02 , DOI: 10.1111/mmi.14901
Marcus A Wittekind ₁ , Andrew Frey ₂ , Abigail E Bonsall ₁ , Paul Briaud ₁ , Rebecca A Keogh ₁ , Richard E Wiemels ₁ , Lindsey N Shaw ₂ , Ronan K Carroll _{1,

3}

Affiliation

Staphylococcus aureus is a Gram-positive commensal that can also cause a variety of infections in humans. S. aureus virulence factor gene expression is under tight control by a complex regulatory network, which includes, sigma factors, sRNAs, and two-component systems (TCS). Previous work in our laboratory demonstrated that overexpression of the sRNA tsr37 leads to an increase in bacterial aggregation. Here, we demonstrate that the clumping phenotype is dependent on a previously unannotated 88 amino acid protein encoded within the tsr37 sRNA transcript (which we named ScrA for S. aureus clumping regulator A). To investigate the mechanism of action of ScrA we performed proteomics and transcriptomics in a ScrA overexpressing strain and show that a number of surface adhesins are upregulated, while secreted proteases are downregulated. Results also showed upregulation of the SaeRS TCS, suggesting that ScrA is influencing SaeRS activity. Overexpression of ScrA in a saeR mutant abrogates the clumping phenotype confirming that ScrA functions via the Sae system. Finally, we identified the ArlRS TCS as a positive regulator of scrA expression. Collectively, our results show that ScrA is an activator of the SaeRS system and suggests that ScrA may act as an intermediary between the ArlRS and SaeRS systems.

中文翻译：

新型蛋白ScrA通过SaeRS双组分系统调节金黄色葡萄球菌毒力基因表达

金黄色葡萄球菌是一种革兰氏阳性共生菌，也可引起人类多种感染。金黄色葡萄球菌毒力因子基因表达受到复杂调控网络的严格控制，其中包括 sigma 因子、sRNA 和双组分系统 (TCS)。我们实验室之前的工作表明，sRNA tsr37 的过度表达会导致细菌聚集增加。在这里，我们证明聚集表型取决于 tsr37 sRNA 转录本中编码的先前未注释的 88 个氨基酸蛋白质（我们将其命名为 ScrA，代表金黄色葡萄球菌c聚集调节因子A ）。为了研究 ScrA 的作用机制，我们在 ScrA 过表达菌株中进行了蛋白质组学和转录组学研究，结果表明许多表面粘附素上调，而分泌的蛋白酶下调。结果还显示 SaeRS TCS 上调，表明 ScrA 正在影响 SaeRS 活性。 saeR突变体中 ScrA 的过度表达消除了聚集表型，证实了 ScrA 通过 Sae 系统发挥作用。最后，我们确定 ArlRS TCS 是scrA表达的正调节因子。总的来说，我们的结果表明 ScrA 是 SaeRS 系统的激活剂，并表明 ScrA 可能充当 ArlRS 和 SaeRS 系统之间的中介。

更新日期：2022-04-02

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