Chlamydia pneumoniae-Specific Inclusion Membrane Proteins

描述（由申请人提供）：肺炎衣原体是一种常见的人类呼吸道病原体，与多种慢性疾病（包括动脉粥样硬化）相关。C.肺炎衣原体与其他衣原体属一样，是一种专性细胞内寄生虫，在称为包涵体的空泡内复制。包涵体膜必须为细菌提供许多功能，包括调节营养物质的可用性，避免与宿主溶酶体融合，提供支持复制的物理条件，以及传递调节衣原体发育阶段的信号。包涵体膜将细菌与宿主细胞质物理隔离，但它通过插入称为Incs（包涵体膜蛋白）的衣原体衍生蛋白而被主动修饰。Inc在C.在沙眼衣原体中，大多数在衣原体进入真核细胞后不久表达，这提高了包含膜的修饰是成功利用真核细胞所需的第一步的可能性。少量的C. Incs。trachomatis和C.鹦鹉热以前已被鉴定和特征化，然而，对C的Incs知之甚少。肺炎。鉴于其作为宿主相互作用蛋白的潜力，Incs代表了阐明衣原体发病机制关键的新过程的有吸引力的靶点。典型的Inc蛋白具有约40-80个氨基酸的独特双叶疏水结构域。使用这种独特的疏水结构域作为指示剂，可以在每个衣原体物种的基因组中鉴定出许多编码Inc候选物的基因。许多Inc蛋白在所有目前测序的衣原体中是常见的，但也有许多预测的Inc蛋白，它们似乎是物种特异性的。 该项目的目标是：（一）对C.定位于衣原体包涵体膜并暴露于宿主细胞质的肺炎球菌特异性Inc; ii.）来鉴定与C.肺炎特异性Inc在包涵体的胞质面。 衣原体在人类中引起一系列疾病，这些疾病因衣原体种类而异。与C.沙眼，呼吸道病原体C.肺炎较为常见，感染可导致更严重的并发症，如心血管疾病。我们建议研究的蛋白质是i）独特的C。肺炎和ii）直接干扰人细胞内的正常功能。

DESCRIPTION (provided by applicant): Chlamydia pneumoniae is a common human respiratory pathogen that has been associated with a variety of chronic diseases including atherosclerosis. C. pneumoniae, like other chlamydial species, is an obligate intracellular parasite that replicates within a vacuole, termed an inclusion. The inclusion membrane must serve numerous functions for the bacteria including regulating nutrient availability, evading fusion with host lysosomes, providing physical conditions to support replication, and transmitting signals that regulate the stages of chlamydial development. The inclusion membrane physically segregates bacteria from the host cytoplasm, yet it is actively modified by insertion of Chlamydia-derived proteins termed Incs (inclusion membrane proteins). Incs have been described most thoroughly in C. trachomatis where most are expressed shortly after chlamydiae enter a eukaryotic cell, raising the possibility that modification of the inclusion membrane is one of the first steps required for successful exploitation of a eukaryotic cell. A small number of Incs of C. trachomatis and C. psittaci have been previously identified and characterized; however, there is little known about the Incs of C. pneumoniae. Given their potential as host-interactive proteins, Incs represent an attractive target for elucidation of novel processes crucial to chlamydial pathogenesis. The typical Inc protein possesses a unique bilobed hydrophobic domain of approximately 40-80 amino acids. Using this unique hydrophobic domain as an indicator, numerous genes encoding Inc candidates can be identified in the genome of each chlamydial species. Many of the Inc proteins are common amongst all currently sequenced chlamydiae, yet there are also numerous predicted Inc proteins, which appear to be species-specific. The goals of this project are: i.) to identify and characterize C. pneumoniae-specific Incs that are localized to the chlamydial inclusion membrane and exposed to the host cytoplasm; ii.) to identify host cell proteins that interact with C. pneumoniae-specific Incs at the cytoplasmic face of the inclusion. Chlamydiae cause a range of diseases in humans that varies depending on the chlamydial species. Unlike the sexually transmitted disease caused by C. trachomatis, the respiratory pathogen C. pneumoniae is more common and infections can contribute to more serious complications such as cardiovascular disease. We propose to study proteins that are i) unique to C. pneumoniae and ii) directly interfere with normal functions within human cells.