The novel protein ScrA acts through the SaeRS two-component system to regulate virulence gene expression in Staphylococcus aureus.
The novel protein ScrA acts through the SaeRS two-component system to regulate virulence gene expression in Staphylococcus aureus.
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DOI：
10.1111/mmi.14901
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发表时间：
2022-05
影响因子：
3.6
通讯作者：
Carroll, Ronan K.
中科院分区：
文献类型：
--
作者：
Wittekind, Marcus A.;Frey, Andrew;Bonsall, Abigail E.;Briaud, Paul;Keogh, Rebecca A.;Wiemels, Richard E.;Shaw, Lindsey N.;Carroll, Ronan K.
金黄色葡萄球菌是一种革兰氏阳性的共生菌，也可引起人类多种感染。金黄色葡萄球菌毒力因子基因的表达受到一个复杂的调控网络的严格控制，该网络包括sigma因子、sRNAs和双组分系统（TCS）。我们实验室之前的工作表明，sRNA tsr37的过表达会导致细菌聚集的增加。在这里，我们证明了结块表型依赖于tsr37 sRNA转录物中编码的先前未注释的88个氨基酸蛋白（我们将其命名为ScrA，代表金黄色葡萄球菌结块调节因子a）。为了研究ScrA的作用机制，我们对一个过表达ScrA的菌株进行了蛋白质组学和转录组学研究，发现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影响SaeRS活性。saeR突变体中ScrA的过表达消除了聚集表型，证实了ScrA通过Sae系统起作用。最后，我们确定了ArlRS TCS是scrA表达的正调节因子。总之，我们的研究结果表明ScrA是SaeRS系统的激活剂，并表明ScrA可能在ArlRS和SaeRS系统之间起中介作用。在这项研究中，我们提出小蛋白ScrA在金黄色葡萄球菌中作为ArlRS和SaeRS两组分系统之间的联系。ArlR正调控scrA表达，由此产生的scrA蛋白激活SaeRS系统，导致Sae调控基因表达增加。Sae系统活性的增加对scrA的表达有负反馈作用，scrA的表达起着断路器的作用。
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. In this study, we propose that the small protein ScrA acts as a link between the ArlRS and SaeRS two‐component systems in Staphylococcus aureus. ArlR positively regulates scrA expression and the resulting ScrA protein activates the SaeRS system, causing increased expression of Sae regulon genes. The increase in Sae system activity has a negative feedback on scrA expression which acts as a circuit breaker.
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DOI：
10.1007/bf00259623
发表时间：
1989-11-01
期刊：
MOLECULAR AND GENERAL GENETICS
影响因子：
--
作者：
JANZON, L;LOFDAHL, S;ARVIDSON, S
通讯作者：
ARVIDSON, S
影响因子：
5.8
作者：
Carroll RK;Robison TM;Rivera FE;Davenport JE;Jonsson IM;Florczyk D;Tarkowski A;Potempa J;Koziel J;Shaw LN
通讯作者：
Shaw LN
影响因子：
6.4
作者：
Carroll RK;Weiss A;Broach WH;Wiemels RE;Mogen AB;Rice KC;Shaw LN
通讯作者：
Shaw LN
影响因子：
6.7
作者：
Cho H;Jeong DW;Liu Q;Yeo WS;Vogl T;Skaar EP;Chazin WJ;Bae T
通讯作者：
Bae T
影响因子：
6.4
作者：
Fey PD;Endres JL;Yajjala VK;Widhelm TJ;Boissy RJ;Bose JL;Bayles KW
通讯作者：
Bayles KW