Characterization of a Transport System within the Chlamydial Inclusion

描述(申请人提供)：沙眼衣原体在全球范围内对人类健康有重大影响。衣原体性病是最常见的可报告疾病，而沙眼是导致传染性失明的主要原因。衣原体作为专性细胞内细菌的要求，以及缺乏遗传上易处理的系统，阻碍了对衣原体的研究。因此，许多关于发病机制的重要问题都没有得到解答。其一是养分获取的方式。其他液泡病原体已被证明通过宿主途径获得营养，在液泡膜内具有开放的通道，或依赖于活跃的运输系统。先前的研究表明，衣原体空泡被称为包涵体，它不与宿主途径相互作用来获得营养，也没有开放的通道。这导致了这样的假设，即衣原体在包涵体膜内拥有一个营养运输系统，将液泡内的细菌连接到宿主细胞质。这将通过使用一种新的分离包涵体和蛋白质组学的方案来探索。病原体能否成功繁殖并随后引起感染，与其获取营养的能力密不可分。这一提议将定义衣原体能够实现这一点的基础，从而使人们对普遍存在于人类社会中的细菌的发病机制有更多的了解。

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.