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

项目摘要/摘要 报告了170多万例沙眼衣原体感染病例 美国疾病控制与预防中心每年都会出现这种疾病，使其成为该国报告最常见的传染病。 沙眼衣原体会引起细胞内感染，我们已经发现 细菌会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，这是大多数人的孤立表面投影 体内分化的细胞；2)静止的宿主细胞重新进入细胞周期。 这些新的宿主-病原体相互作用可能被错过了，因为 传统的衣原体细胞培养感染模型使用的是缺乏原代细胞的循环细胞 纤毛。在目标1中，我们将确定衣原体感染是否导致初级纤毛的丧失。 通过宿主细胞的AURA调节途径诱导纤毛分解。在……里面 目标2，我们将调查衣原体如何导致细胞周期重新进入，并将确定 这种感染涉及并失调了已知的细胞周期重新进入的细胞调节。 和进步。在目标3中，我们将研究衣原体是否以及如何导致初生纤毛丧失。 细胞周期重入促进衣原体感染。我们还将调查这些是否 两种寄主与病原菌的相互作用在功能上相互联系或相互独立。 这些研究的成功完成将定义两个新的宿主-病原体相互作用： 目前还没有已知的微生物导致初级纤毛丧失，只有病毒，而不是细菌，有。 已被证明能使静止的宿主细胞重新进入细胞周期。干预措施 预防衣原体引起的初级纤毛丢失和细胞周期重入可能导致一种新的 针对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.