Investigating the small peptide Tsr37, its role in virulence, and activation of the SaeRS two component system in Staphylococcus aureus

研究金黄色葡萄球菌中的小肽 Tsr37、其毒力作用以及 SaeRS 二组分系统的激活

基本信息

批准号：
10372077
负责人：
Ronan Carroll
金额：
$ 18.88万
依托单位：
OHIO UNIVERSITY ATHENS
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-15 至 2024-02-29
项目状态：
已结题

项目摘要

PROJECT SUMMARY/ABSTRACT Staphylococcus aureus is both a commensal of humans and a highly dangerous bacterial pathogen. S. aureus pathogenesis is mediated by a large repertoire of secreted and cell wall-associated virulence factors. To mount successful infections the bacteria must regulate expression of the genes encoding these virulence factors in a temporal and spatial manner. Two component signal transduction systems (TCS) are one type of regulatory circuit that bacterial cells use to sense their environment and modify gene expression accordingly. The Sae TCS is a global regulator of secreted protein production in S. aureus and a variety of well-studied virulence factors are known to be directly controlled by the Sae system. Activity of the Sae system is dependent on the balance between the kinase and phosphatase activities of the sensor protein SaeS. Human neutrophil peptide 1 (HNP-1) is known to activate SaeS kinase activity, while the Sae auxiliary proteins SaePQ induce phosphatase activity. Recent work in our laboratory has identified a potent, novel activator of the Sae system. Overexpression of the tsr37 gene in S. aureus results in a dramatic increase in Sae activity and upregulation of Sae target genes. In this proposal we will investigate the nature of the tsr37 gene product, investigate how tsr37 activates the Sae system, and determine the contribution of tsr37 to virulence. In addition, we will study the in vivo expression profile of tsr37 to determine when and where it is expressed during systemic infection. We anticipate that the results from this study will demonstrate that a short protein, Tsr37, acts as a potent activator of the Sae TCS. Understanding how a small peptide interacts with, and activates, the Sae system could inform future studies to design Sae inhibitors which could be used as a novel therapeutic to treat S. aureus infection.

项目概要/摘要金黄色葡萄球菌既是人类的共生菌，也是一种高度危险的细菌病原体。金黄色葡萄球菌发病机制是由大量分泌的和细胞壁相关的毒力因子介导的。安装成功感染细菌必须调节编码这些毒力因子的基因的表达时间和空间方式。双组分信号转导系统 (TCS) 是一种监管类型细菌细胞用来感知环境并相应地修改基因表达的电路。萨埃 TCS 是金黄色葡萄球菌分泌蛋白生产和多种经过充分研究的毒力的全局调节剂已知因素由 Sae 系统直接控制。 Sae 系统的活动取决于传感器蛋白 SaeS 的激酶和磷酸酶活性之间的平衡。人中性粒细胞肽 1 (HNP-1) 已知可激活 SaeS 激酶活性，而 Sae 辅助蛋白 SaePQ 会诱导磷酸酶活性。我们实验室最近的工作发现了一种有效的新型 Sae 系统激活剂。金黄色葡萄球菌中 tsr37 基因的过度表达导致 Sae 活性显着增加并上调 Sae目标基因。在本提案中，我们将研究 tsr37 基因产物的性质，研究如何 tsr37 激活 Sae 系统，并确定 tsr37 对毒力的贡献。此外，我们还将学习 tsr37 的体内表达谱以确定其在全身感染期间表达的时间和地点。我们预计这项研究的结果将证明短蛋白 Tsr37 可以作为有效的 Sae TCS 的激活剂。了解小肽如何与 Sae 系统相互作用并激活该系统可以为未来设计 Sae 抑制剂的研究提供信息，该抑制剂可用作治疗金黄色葡萄球菌的新型疗法。金黄色葡萄球菌感染。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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

新型蛋白质 ScrA 通过 SaeRS 双组分系统发挥作用，调节金黄色葡萄球菌的毒力基因表达。

DOI：
发表时间：
2022-05
期刊：
影响因子：
3.6
作者：
Wittekind, Marcus A;Frey, Andrew;Bonsall, Abigail E;Briaud, Paul;Keogh, Rebecca A;Wiemels, Richard E;Shaw, Lindsey N;Carroll, Ronan K
通讯作者：
Carroll, Ronan K

The Small Protein ScrA Influences Staphylococcus aureus Virulence-Related Processes via the SaeRS System.

小蛋白 ScrA 通过 SaeRS 系统影响金黄色葡萄球菌毒力相关过程。