The Small Protein ScrA Influences Staphylococcus aureus Virulence-Related Processes via the SaeRS System.
The Small Protein ScrA Influences Staphylococcus aureus Virulence-Related Processes via the SaeRS System.
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小蛋白 ScrA 通过 SaeRS 系统影响金黄色葡萄球菌毒力相关过程。
DOI：
10.1128/spectrum.05255-22
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发表时间：
2023-06-15
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
金黄色葡萄球菌是一种革兰氏阳性共生机会致病菌，能够引起从轻度皮肤感染到危及生命的心内膜炎和中毒性休克综合征等疾病。引起如此一系列疾病的能力是由于复杂的金黄色葡萄球菌调节网络控制着各种毒力因子，包括粘附素、溶血素、蛋白酶和脂肪酶。该调控网络由蛋白质和 RNA 元件控制。我们之前发现了一种名为 ScrA 的新型调节蛋白，当它过度表达时，会导致 SaeRS 调节子的活性和表达增加。在这项研究中，我们进一步探讨了 ScrA 的作用，并检查了 scrA 基因破坏对细菌细胞的影响。这些结果表明，scrA 是几种毒力相关过程所必需的，并且在许多情况下，scrA 突变体的表型与在过度表达 ScrA 的细胞中观察到的表型相反。有趣的是，虽然大多数 ScrA 介导的表型似乎依赖于 SaeRS 系统，但我们的结果还表明，ScrA 在调节溶血活性时也可能独立于 SaeRS 发挥作用。最后，使用小鼠感染模型，我们证明 scrA 是毒力所必需的，可能以器官特异性的方式。重要性 金黄色葡萄球菌是几种可能危及生命的感染的原因。各种各样的毒素和毒力因子导致了如此广泛的感染。然而，各种毒素或毒力因子需要复杂的调节来控制细菌遇到的所有不同条件下的表达。了解错综复杂的监管系统网络有助于开发对抗金黄色葡萄球菌感染的新方法。在这里，我们证明了我们实验室先前鉴定的小蛋白 ScrA 通过 SaeRS 全球监管系统影响多种毒力相关功能。这些发现将 ScrA 添加到金黄色葡萄球菌不断增长的毒力调节因子列表中。
Staphylococcus aureus is a Gram-positive commensal and opportunistic pathogen able to cause diseases ranging from mild skin infections to life-threatening endocarditis and toxic shock syndrome. The ability to cause such an array of diseases is due to the complex S. aureus regulatory network controlling an assortment of virulence factors, including adhesins, hemolysins, proteases, and lipases. This regulatory network is controlled by both protein and RNA elements. We previously identified a novel regulatory protein called ScrA, which, when overexpressed, leads to the increased activity and expression of the SaeRS regulon. In this study, we further explore the role of ScrA and examine the consequences to the bacterial cell of scrA gene disruption. These results demonstrate that scrA is required for several virulence-related processes, and in many cases, the phenotypes of the scrA mutant are inverse to those observed in cells overexpressing ScrA. Interestingly, while the majority of ScrA-mediated phenotypes appear to rely on the SaeRS system, our results also indicate that ScrA may also act independently of SaeRS when regulating hemolytic activity. Finally, using a murine model of infection, we demonstrate that scrA is required for virulence, potentially in an organ-specific manner. IMPORTANCE Staphylococcus aureus is the cause of several potentially life-threatening infections. An assortment of toxins and virulence factors allows such a wide range of infections. However, an assortment of toxins or virulence factors requires complex regulation to control expression under all of the different conditions encountered by the bacterium. Understanding the intricate web of regulatory systems allows the development of novel approaches to combat S. aureus infections. Here, we have shown that the small protein ScrA, which was previously identified by our laboratory, influences several virulence-related functions through the SaeRS global regulatory system. These findings add ScrA to the growing list of virulence regulators in S. aureus.
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影响因子：
6.7
作者：
Crosby HA;Schlievert PM;Merriman JA;King JM;Salgado-Pabón W;Horswill AR
通讯作者：
Horswill AR
影响因子：
3.7
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Jefferson KK
影响因子：
6.7
作者：
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通讯作者：
Horswill, Alexander R.
影响因子：
3.5
作者：
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通讯作者：
IZAKI, K
影响因子：
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Fey PD;Endres JL;Yajjala VK;Widhelm TJ;Boissy RJ;Bose JL;Bayles KW
通讯作者：
Bayles KW