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：
10656471
负责人：
CHRISTINE SUETTERLIN
金额：
$ 54.23万
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/10656471
关键词：
Antibodies Bacteria Biology Cell Culture Techniques Cell Cycle Cell Cycle Progression Cell Differentiation process Cell Line Cell Surface Extensions Cells 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 Learning Link Malignant Neoplasms Measures Methods Microbe Microscopy Modeling Molecular Organelles Pathway interactions Phenotype Physicians Physiological Proliferating 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/摘要报告了超过170万病例的沙眼衣原体感染。 CDC每年使其成为该国最常见的传染病。 C.沙眼引起细胞内感染，我们发现这是细菌对感染的宿主细胞产生两种影响，以前尚未描述：1）损失主要纤毛，这是大多数孤立的表面投影分化体内的细胞； 2）将静止的宿主细胞重新输入到细胞周期中。这些新颖的宿主病原体相互作用可能被错过了常规衣原体细胞培养感染模型使用缺乏主要的循环细胞纤毛。在AIM 1中，我们将确定衣原体感染是否会导致原发性纤毛的流失通过通过宿主细胞的AURA调节途径诱导纤毛拆卸。在 AIM 2，我们将研究衣原体如何导致细胞周期重新进入，并确定是否是否感染涉及并失调的细胞周期重新进入的已知细胞调节剂和进展。在AIM 3中，我们将研究衣原体诱导的原发性纤毛损失细胞周期重新进入衣原体感染。我们还将调查是否两种宿主 - 病原体相互作用在功能上连接或彼此独立。这些研究的成功完成将定义两种新型的宿主 - 病原体相互作用：已知没有微生物会导致原发性纤毛损失，只有病毒，但没有细菌被证明会导致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原发性纤毛损失和细胞周期重新进入可能导致新颖的针对衣原体感染的治疗策略。