Characterization of a Transport System within the Chlamydial Inclusion

描述（由申请方提供）：沙眼衣原体对全球人类健康有重大影响。衣原体性传播疾病是最常见的可报告疾病，而沙眼是传染性失明的主要原因。衣原体的研究受到其作为专性细胞内细菌的需求沿着缺乏遗传学上易于处理的系统的阻碍。因此，许多关于发病机制的重要问题仍然没有答案。一个是养分获取的方式。其他液泡病原体已被证明通过宿主途径获得营养物质，在液泡膜内具有开放通道，或依赖于主动运输系统。先前的研究表明，被称为内含物的chlamdyial液泡不与宿主途径相互作用以获得营养，也没有开放的通道。这导致了一种假设，即衣原体在包涵体膜内拥有一个营养转运系统，该系统将液泡内的细菌与宿主细胞质联系起来。这将通过使用一种新的协议来分离夹杂物和蛋白质组学进行探索。病原体成功繁殖并随后引起感染与其获取营养的能力密不可分。这项提议将确定衣原体能够实现这一目标的基础，从而深入了解在人类社会中普遍存在的细菌的发病机制。

DESCRIPTION (provided by applicant): Chlamydia trachomatis has a significant impact on human health worldwide. Chlamydial STD is the most common reportable disease while Trachoma accounts for the leading cause of infectious blindness. Studies on Chlamydia are hampered by its demands as an obligate intracellular bacteria, along with the lack of a genetically tractable system. Many important questions concerning the pathogenesis are thus left unanswered. One being the manner in which nutrient acquisition occurs. Other vacuolar pathogens have been documented to obtain nutrients via host pathways, having open channels within the vacuolar membrane, or relying on an active transport system. Previous research has shown that the chlamdyial vacuole, termed the inclusion, does not interact with host pathways to garner nutrients nor does it have open channels. This leads to the hypothesis that Chlamydia possess a nutrient transport system within the inclusion membrane that links the bacteria within the vacuole to the host cytoplasm. This will be explored via the usage of a novel protocol to isolate inclusions and proteomics. The success of a pathogen to propagate and subsequently cause infection is inextricably linked to its ability to acquire nutrients. This proposal will define the basis through which Chlamydia is able to accomplish this, and thus give much insight into the pathogenesis of a bacteria that is pervasive within human society.