Department of Biological Sciences, Ohio University, Athens, Ohio, USA.
Microbiol Spectr. 2023 Jun 15;11(3):e0525522. doi: 10.1128/spectrum.05255-22. Epub 2023 May 8.
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 gene disruption. These results demonstrate that is required for several virulence-related processes, and in many cases, the phenotypes of the 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 is required for virulence, potentially in an organ-specific manner. 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.
金黄色葡萄球菌是一种革兰氏阳性共生菌和机会致病菌，能够引起从轻度皮肤感染到威胁生命的心内膜炎和中毒性休克综合征等多种疾病。它具有引起如此多种疾病的能力，是由于其复杂的金黄色葡萄球菌调控网络控制着各种毒力因子，包括黏附素、溶血素、蛋白酶和脂肪酶。这个调控网络受到蛋白质和 RNA 元件的控制。我们之前鉴定了一种名为 ScrA 的新型调控蛋白，当过度表达时，会导致 SaeRS 调控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，并检查了基因敲除对细菌细胞的后果。这些结果表明， 对于几种与毒力相关的过程是必需的，在许多情况下， 突变体的表型与 ScrA 过表达细胞中观察到的表型相反。有趣的是，虽然 ScrA 介导的大多数表型似乎依赖于 SaeRS 系统，但我们的结果也表明，ScrA 在调节溶血活性时也可能独立于 SaeRS 发挥作用。最后，我们使用感染的小鼠模型证明了 对于毒力是必需的，可能具有器官特异性。金黄色葡萄球菌是几种潜在的威胁生命的感染的原因。各种各样的毒素和毒力因子允许如此广泛的感染。然而，各种毒素或毒力因子需要复杂的调控来控制在细菌遇到的所有不同条件下的表达。了解复杂的调控系统网络允许开发新的方法来对抗金黄色葡萄球菌感染。在这里，我们已经表明，我们实验室之前鉴定的小蛋白 ScrA 通过 SaeRS 全局调控系统影响几种与毒力相关的功能。这些发现将 ScrA 添加到金黄色葡萄球菌中不断增长的毒力调控因子列表中。
