Primary cilia loss and cell cycle re-entry in Chlamydia-infected cells

项目概要/摘要 向世界卫生组织报告的沙眼衣原体感染病例超过170万例， 疾病控制和预防中心每年，使其成为最常见的报告传染病在该国。 C.沙眼衣原体引起细胞内感染，我们已经发现， 细菌对受感染的宿主细胞产生两种以前没有的影响， 描述：1）失去初级纤毛，这是一个孤立的表面投影在大多数 分化的细胞在体内; 2）重新进入静止的宿主细胞进入细胞周期。 这些新的宿主-病原体相互作用可能被错过了， 常规的衣原体细胞培养感染模型使用缺乏初级免疫原性的循环细胞， 纤毛。在目标1中，我们将确定衣原体感染是否会导致初级纤毛丧失 通过宿主细胞的AurA调节途径诱导纤毛解体。在 目的2，我们将研究衣原体如何导致细胞周期重新进入，并将确定是否 感染涉及并失调已知的细胞周期再进入的细胞调节因子 和进步。在目标3中，我们将研究衣原体是否以及如何引起初级纤毛损失 和细胞周期再进入促进衣原体感染。我们还将调查这些 两种宿主-病原体相互作用在功能上相互关联或相互独立。 成功完成这些研究将确定两种新的宿主-病原体相互作用： 没有已知的微生物会引起初级纤毛的损失，只有病毒，而不是细菌， 已经显示出引起静止的宿主细胞重新进入细胞周期。干预措施来 防止衣原体诱导的初级纤毛损失和细胞周期重新进入可能导致一种新的 衣原体感染的治疗策略。

Project Summary/Abstract More than 1.7 million cases of Chlamydia trachomatis infections are reported to the CDC each year, making it the most commonly reported infectious disease in the country. C. trachomatis causes an intracellular infection, and we have discovered that this bacterium causes two effects on an infected host cell that have not been previously described: 1) loss of the primary cilium, which is a solitary surface projection on most differentiated cells in the body; 2) re-entry of a quiescent host cell into the cell cycle. These novel host-pathogen interactions may have been missed because the conventional Chlamydia cell culture infection model uses cycling cells that lack primary cilia. In Aim 1, we will determine if Chlamydia infection causes loss of the primary cilium by inducing cilia disassembly through the AurA regulatory pathway of the host cell. In Aim 2, we will investigate how Chlamydia causes cell cycle re-entry and will determine if the infection involves and dysregulates known cellular regulators of cell cycle re-entry and progression. In Aim 3, we will study if and how Chlamydia-induced primary cilia loss and cell cycle re-entry promote the chlamydial infection. We will also investigate if these two host-pathogen interaction are functionally linked or independent from each other. Successful completion of these studies will define two novel host-pathogen interactions: no microbe is known to cause primary cilia loss, and only viruses, but not bacteria, have been shown to cause quiescent host cells to re-enter the cell cycle. Interventions to prevent Chlamydia-induced primary cilia loss and cell cycle re-entry may lead to a novel therapeutic strategy against Chlamydia infections.