How bacteria corrupt the host vesicular trafficking: Interfering with host SNAREs

描述(申请人提供)：沙眼衣原体是一种细胞内细菌，是性传播疾病和传染性失明的主要原因。衣原体的生存在很大程度上依赖于两个基本过程：1)保护其感染性胞内隔室(所谓的包涵体)不受溶酶体降解途径的影响；2)劫持寄主隔室以获得生长包涵体所需的营养物质。为了执行这两个事件，沙眼衣原体进化成在操纵膜融合并促进其生存方面非常有效。尽管衣原体和宿主囊泡运输之间的这种密切联系很重要，但关于这种细菌对宿主膜融合机制的影响，即所谓的陷阱，人们知之甚少。衣原体是否广泛使用陷阱来控制宿主的囊泡运输，并促进它们在细胞内的生存？我们采用一种创新的多学科方法，试图确定沙眼衣原体是否(I)使用多个SNAR样蛋白来顺序地阻断参与内吞/溶酶体途径的不同宿主SNAR复合体并保护其包涵体免受破坏，以及(Ii)招募参与分泌途径的宿主圈套来劫持宿主小泡并促进其包涵体的生长。多个衣原体陷阱样蛋白的特征将为科学家提供基本工具，以筛选它们在包括伤寒沙门氏菌和结核分枝杆菌在内的其他主要人类病原体的蛋白质组中的存在，从而开辟新的研究途径。

DESCRIPTION (provided by applicant): Chlamydia trachomatis is an intracellular bacterium that is a major cause of sexually transmitted diseases and infectious blindness. Chlamydia's survival largely relies on two fundamental processes 1) protecting its infectious intracellular compartment (so-called inclusion) from the lysosomal degradative pathway and 2) hijacking host compartments to acquire nutrients and material necessary to grow the inclusion. To perform both these events, C. trachomatis evolved to be extraordinarily efficient at manipulating membrane fusion and promote its survival. Despite the importance of this intimate connection between Chlamydia and host vesicular trafficking, very little is known regarding the impact of this bacterium on the host membrane fusion machinery, the so-called SNAREs. Do Chlamydiae extensively co-opt SNAREs to control the host vesicular trafficking and promote their survival inside the cell? Using an innovative multidisciplinary approach, we seek to determine whether C. trachomatis (i) uses multiple SNARE-like proteins to sequentially block different host SNARE complexes involved in the endocytic/lysosomal pathway and protect its inclusion from destruction and (ii) recruits host SNAREs involved in the secretory pathway to hijack host vesicles and promote the growth of its inclusion. The characterization of multiple chlamydial SNARE-like proteins will give scientists the fundamental tools to screen for their presence in the proteome of other major human pathogens, including Salmonella typhi, and Mycobacterium tuberculosis, thus opening new avenues of research.