Host-pathogen interactions controlling Chlamydia developmental cycle

总结 沙眼衣原体是细菌性传播感染的主要原因。没有一种疫苗是 available.感染通常无症状，导致生殖器官的长期损害， 对人体健康的有害影响，从盆腔炎到不孕不育。发病机制与 生殖道上皮细胞的侵入引发的宿主炎症反应， 胞内病原体衣原体细胞内生活方式的一个标志和关键方面是其双相性 发育周期，在此期间细菌在感染（EB）和复制（RB）形式之间交替 在一个被称为内含物的膜结合区室的腔内。管理的机制 对发育周期的进展知之甚少。在这里，我们描述一个衣原体条件 包含膜蛋白的突变体。突变体表现出严重的，但可互补的， 发育周期早期阶段的缺陷，最有可能是在EB到RB的转化过程中。此外，该公司 蛋白质与宿主因子相互作用，宿主因子参与细菌退出发育周期的后期阶段。 通过挤压将细胞挤出。我们建议检验这一假设，即这种Inc蛋白在早期（目的1）和晚期（目的2）起双重作用。 晚期（Aim 2），并确定其对发病机制的贡献（Aim 3）。通过 利用细胞生物学，细菌遗传学，转录组学，蛋白质组学和体内方法，我们的研究将 进一步了解宿主-衣原体相互作用的分子机制， 发展周期。总之，我们的工作有可能确定治疗靶点，以阻止 与这种重要的性传播病原体有关的传播和发病机制。

SUMMARY Chlamydia trachomatis is the leading cause of sexually transmitted infections of bacterial origin. No vaccine is available. Infections are often asymptomatic, leading to long-term damage of the reproductive organs and deleterious effects on human health ranging from pelvic inflammatory disease to infertility. Pathogenesis is linked to a host inflammatory response triggered by the invasion of the genital tract epithelium with this obligate intracellular pathogen. A hallmark and critical aspect of Chlamydia intracellular life style is its bi-phasic developmental cycle, during which the bacteria alternate between infectious (EB) and replicative (RB) forms within the lumen of a membrane-bound compartment called the inclusion. The mechanisms that govern progression through the developmental cycle are poorly understood. Here we describe a Chlamydia conditional mutant in an inclusion membrane protein. The mutant displays a severe, yet complementable, developmental defect in the early stages of the developmental cycle, most likely during EB to RB conversion. Moreover, this Inc protein interacts with a host factor involved in the late stages of the developmental cycle, when the bacteria exit the cell via extrusion. We propose to test the hypothesis that this Inc protein plays a dual role early (Aim 1) and late (Aim2) during the developmental cycle and to determine its contribution to pathogenesis (Aim 3). Through the use of cell biology, bacterial genetics, transcriptomics, proteomics and in vivo approaches, our studies will further our understanding of the molecular mechanisms governing the host-Chlamydia interactions that control the developmental cycle. Altogether our work has the potential to identify therapeutic targets to block transmission of and pathogenesis associated with this important sexually transmitted pathogen.