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

衣原体感染细胞中的初级纤毛丢失和细胞周期重新进入

基本信息

批准号：
10436218
负责人：
CHRISTINE SUETTERLIN
金额：
$ 55.17万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-17 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10436218
关键词：
Antibodies Bacteria Biology Cell Culture Techniques Cell Cycle Cell Cycle Progression Cell Differentiation process Cell Line Cell surface Cells Centers for Disease Control and Prevention (U.S.)Centrosome Chlamydia Chlamydia Infections Chlamydia trachomatis Cilia Communicable Diseases Country Data Development Disease Notification Environment Epithelial Cells Flow Cytometry G1/S Transition Goals Growth HDAC6 gene Infection Intervention Knowledge Lead Learning Link Malignant Neoplasms Measures Methods Microbe Microscopy Modeling Molecular Organelles Pathway interactions Phenotype Physicians Physiological Reader Regulatory Pathway Reporter Reporting Research Personnel S phase Scientist Sexually Transmitted Diseases Signal Transduction Small Interfering RNA Surface Testing Time Virus aurora kinase A genital infection human pathogen inhibitor metaplastic cell transformation novel novel therapeutic intervention pathogen prevent reproductive tract response

项目摘要

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.

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。