Activities of enteropathogenic/enterohemorrhagic E. coli effector proteins

肠致病性/肠出血性大肠杆菌效应蛋白的活性

• 批准号: 215984020
• 负责人: Dr. Kerstin Maria Ewen
• 金额: --
• 依托单位: Department of Pathology
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/215984020?language=en
• 关键词: Activities; enteropathogenic; enterohemorrhagic; E.; coli

Diarrhoeal disease is a major human health problem which can be held accountable for roughly 2 million deaths each year. Among the bacterial agents causing diarrhoeal disease are the enteropathogenic E. coli (EPEC) and the closely related enterohemorrhagic E. coli (EHEC). Both, EPEC and EHEC cause disease by intimately attaching to host intestinal cells, and inducing the degeneration of absorptive microvilli. Although both are extracellular pathogen, they inject a plethora of effector proteins into the host cell, which affect many cellular functions. One extensively studied example of such a subversion of host cell mechanisms is the reorganisation of the cellular actin cytoskeleton to form actin pedestals under the attaching bacteria, a process that is known to be crucial for efficient colonisation. While the mode of action of some E. coli effector proteins has been explained, there are still a number of proteins delivered to the host cell by EPEC/EHEC whose function is unknown to date. The aim of the proposed research project is to elucidate the functions of selected EHEC/EPEC effector proteins in the eukaryotic cell and also to further throw light on the different mechanisms used by these bacteria to manipulate and infect the host cell. As many bacterial effector proteins have redundant and/or cooperative functions, they have little or no known phenotype when mutated in EPEC/EHEC. Thus, the genetic approach will be complemented and backed up by in vitro studies. These will entail the cloning and purification of selected bacterial effector proteins, which will allow for the identification of novel eukaryotic targets. The protein-protein interaction identified in vitro will then be validated using cell culture based models.

腹泻病是一个重大的人类健康问题，每年约有200万人死亡。引起腹泻病的细菌有致病性肠出血性大肠埃希菌(EPEC)和与之密切相关的肠出血性大肠杆菌(EHEC)。EPEC和EHEC都是通过与宿主肠道细胞紧密结合，诱导吸收微绒毛变性而致病的。虽然两者都是细胞外病原体，但它们向宿主细胞注入过多的效应蛋白，影响许多细胞功能。这种对宿主细胞机制的颠覆的一个广泛研究的例子是细胞肌动蛋白细胞骨架的重组，以形成附着在细菌下的肌动蛋白基座，这一过程被认为是有效定植的关键。虽然一些大肠杆菌效应蛋白的作用方式已经被解释，但仍有一些蛋白通过EPEC/EHEC递送到宿主细胞，其功能迄今尚不清楚。该研究项目的目的是阐明选定的EHEC/EPEC效应蛋白在真核细胞中的功能，并进一步阐明这些细菌操纵和感染宿主细胞的不同机制。由于许多细菌效应蛋白具有冗余和/或协同功能，它们在EPEC/EHEC中突变时几乎没有或没有已知的表型。因此，遗传方法将得到体外研究的补充和支持。这将需要克隆和纯化选定的细菌效应蛋白，这将使识别新的真核靶标成为可能。然后将使用基于细胞培养的模型来验证在体外确定的蛋白质-蛋白质相互作用。