Salmonella effectors that modulate host responses to infection

调节宿主对感染反应的沙门氏菌效应器

• 批准号: G0800148/1
• 负责人: David Holden
• 金额: $ 180.24万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0800148%2F1
• 关键词: Salmonella; effectors; modulate; host; responses

Salmonella species are important bacterial pathogens causing a variety of human diseases, such as gastroenteritis and typhoid. Salmonella can invade and grow inside the cells of its host, including specialised white blood cells (macrophages) whose function is to destroy potential pathogens. Having entered host cells, Salmonella resides within a membranous sac (vacuole), and transfers through it a large number of virulence proteins, some of which are inserted into the vacuole membrane itself. These bacterial proteins have several different functions: some of them enable bacteria to grow inside the vacuole, and recent evidence indicates that others block the ability of host cells to send alarm signals to other cells to mount an immune response. A third set of proteins causes the infected cells to die after bacteria have replicated within them. We have identified some of the proteins involved and have gained some insights as to how they work. The proposed research involves detailed investigations into their functions at the molecular level, including the identification of the cellular ?targets? with which they must interact to interfere with the host. In the process we are likely to discover new processes of pathogen and host cell biology, which could have implications for other important intracellular pathogens. Our work is also likely to provide valuable information for the design of novel, rationally designed vaccines, which are essential to provide effective long term protection against Salmonella and other bacterial pathogens.Information about our work has been communicated to the lay public through radio interviews and newspaper and magazine articles, following press releases from Imperial College and the scientific journals which publish our work. For example, I have been interviewed on the Today Programme (BBC Radio 4), and articles on our work have appeared in the Daily Telegraph and The Financial Times.

沙门氏菌属是引起胃肠炎、伤寒等多种人类疾病的重要病原菌。沙门氏菌可以侵入宿主细胞并在其中生长，包括专门的白色血细胞（巨噬细胞），其功能是摧毁潜在的病原体。进入宿主细胞后，沙门氏菌驻留在膜囊（液泡）中，并通过它转移大量毒力蛋白，其中一些插入液泡膜本身。这些细菌蛋白具有几种不同的功能：其中一些使细菌能够在液泡内生长，最近的证据表明，其他蛋白阻止宿主细胞向其他细胞发送警报信号以启动免疫反应的能力。第三组蛋白质导致感染的细胞在细菌在其中复制后死亡。我们已经确定了一些相关的蛋白质，并对它们的工作原理有了一些了解。拟议中的研究涉及详细的调查，他们的功能在分子水平上，包括识别的细胞？目标？它们必须与之相互作用以干扰宿主。在这个过程中，我们可能会发现病原体和宿主细胞生物学的新过程，这可能对其他重要的细胞内病原体产生影响。我们的工作也可能为设计新颖的、合理设计的疫苗提供有价值的信息，这些疫苗对于提供有效的长期保护以对抗沙门氏菌和其他细菌病原体是必不可少的。关于我们工作的信息已经通过广播采访和报纸和杂志文章，以及帝国理工学院和发表我们工作的科学期刊的新闻稿传达给公众。例如，我接受了《今日》节目（BBC Radio 4）的采访，《每日电讯报》和《金融时报》也刊登了关于我们工作的文章。