Osmotic stress regulation and the role of cyclic di-adenosine monophosphate (c-di-AMP) in Staphylococcus aureus

金黄色葡萄球菌的渗透应激调节和环二腺苷单磷酸 (c-di-AMP) 的作用

• 批准号: 318765828
• 负责人: Dr. Christopher Schuster
• 金额: --
• 依托单位: Section of Microbiology
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/318765828?language=en
• 关键词: Osmotic; stress; regulation; role; cyclic

The work described in this proposal aims to provide insight into how osmotic stress is regulated in Staphylococcus aureus and what role c-di-AMP plays in this process. S. aureus is an opportunistic pathogen that causes a variety of diseases such as bacteremia, toxic shock syndrome, endocarditis and sepsis. It is also a common food borne pathogen, which is in part mediated by its ability to withstand high external concentrations of salt, a technique often used for the preservation of food. So far, the mechanism(s) behind this osmotic stress resistance is only poorly understood and the ability to impede this process could help to prevent S. aureus food borne infections. In general, S. aureus reacts to osmotic upshock with the import of potassium ions and small organic molecules called compatible solutes to counteract the efflux of water. Current data indicate that the recently discovered second messenger cyclic di-adenosine monophosphate (c-di-AMP) is involved in this process, as several c-di-AMP receptor proteins in S. aureus regulate the expression or activity of potassium transport systems. In an as yet unpublished screen for additional c-di-AMP binding proteins, a novel c-di-AMP receptor protein, likely involved in the uptake of osmolytes, was discovered. This project therefore aims to functionally characterize this osmolyte transporter in depth, elucidate the regulatory role of c-di-AMP on its function and determine its physiological role in S. aureus. In order to gain a greater understanding of how S. aureus reacts to salt stress in general, a TN-seq based approach will be used to determine on a genome wide level which genes are essential in S. aureus under salt stress conditions and how c-di-AMP is involved in this process. Promising candidate genes will then be further validated and characterized. Together, these experiments will contribute to our understanding of how S. aureus adapts and survives in high salt environments and what role c-di-AMP plays in this context.

本提案中描述的工作旨在深入了解金黄色葡萄球菌中渗透压是如何调节的，以及c-di-AMP在这一过程中起什么作用。S.金黄色葡萄球菌是一种机会致病菌，可引起多种疾病，如菌血症、中毒性休克综合征、心内膜炎和败血症。它也是一种常见的食源性病原体，部分原因是它能够承受高浓度的外部盐，这是一种经常用于保存食物的技术。到目前为止，这种渗透胁迫抗性背后的机制还知之甚少，阻碍这一过程的能力可能有助于防止S。金黄色葡萄球菌食源性感染。总的来说，S.金黄色葡萄球菌对渗透性上激反应，输入钾离子和称为相容溶质的小有机分子以抵消水的流出。目前的数据表明，最近发现的第二信使环二磷酸腺苷（c-di-AMP）参与了这一过程，因为S.金黄色葡萄球菌调节钾转运系统的表达或活性。在尚未发表的筛选额外的c-di-AMP结合蛋白中，发现了一种新的c-di-AMP受体蛋白，可能参与渗透剂的摄取。因此，本项目旨在深入研究这种渗透调节转运蛋白的功能，阐明c-di-AMP对其功能的调节作用，并确定其在S.金黄色。为了更好地理解S。金黄色葡萄球菌一般对盐胁迫反应，基于TN-seq的方法将用于在全基因组水平上确定哪些基因在金黄色葡萄球菌中是必需的。金黄色葡萄球菌在盐胁迫条件下的作用以及c-di-AMP如何参与这一过程。然后将进一步验证和表征有希望的候选基因。总之，这些实验将有助于我们理解S。金黄色葡萄球菌适应和生存在高盐环境和什么样的作用c-di-AMP在这种情况下发挥。