Chlamydial Manipulation of Host Apoptosis

衣原体操纵宿主细胞凋亡

• 批准号: 7031922
• 负责人: GUANGMING ZHONG
• 金额: $ 32.85万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-15 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7031922
• 关键词: Chlamydiaceae; apoptosis; cofactor; infection

DESCRIPTION (provided by applicant): --Mechanisms of Chlamydial Manipulation of Host Cell Apoptosis-- Chlamydial infection in humans imposes a major health problem in both developing and developed nations. Urogenital tract infection with C. trachomatis species is a leading cause of sexually transmitted bacterial diseases and is also linked to certain type of cervical carcinoma while respiratory infection with C. pneumoniae species is associated with atherosclerosis, a major vascular condition for cardio-cerebral fatality. Although the species C. psittaci is primarily an animal pathogen, humans are also susceptible to C. psittaci infection, developing life-threatening pneumonia. Since humans can acquire infection via aerosolized animal feces that are contaminated with C. psittaci organisms, CDC has once listed C. psittaci as a category B agent for biodefense. These chlamydia-induced or -associated pathologies are largely due to Chlamydial ability to either productively replicate or to achieve a long-term persistence within a cytoplasmic vacuole of eukaryotic cells, which are aided by the Chlamydial unique intracellular biphasic life cycle and the Chlamydial ability to evade host defense. The current proposal is designed to understand how chlamydia evades a very important host defense effector mechanism-apoptosis. We have previously demonstrated that chlamydia possesses a potent anti-apoptotic activity, which may contribute to the Chlamydial ability to survive in the infected hosts for long periods of time. By identifying the molecule(s) responsible for the Chlamydial anti-apoptotic activity and understanding how the anti-apoptotic molecules work as proposed in the current project, we may be able to develop reagents/approaches for blocking the Chlamydial anti-apoptotic activity and preventing chlamydia-induced pathologies.

描述（由申请人提供）： --衣原体操纵宿主细胞凋亡的机制--人类衣原体感染给发展中国家和发达国家带来了重大的健康问题。沙眼衣原体的泌尿生殖道感染是性传播细菌性疾病的主要原因，也与某些类型的宫颈癌有关，而肺炎衣原体的呼吸道感染则与动脉粥样硬化有关，动脉粥样硬化是导致心脑死亡的主要血管疾病。尽管鹦鹉热衣原体主要是一种动物病原体，但人类也容易受到鹦鹉热衣原体感染，发展成危及生命的肺炎。由于人类可以通过被鹦鹉热衣原体污染的雾化动物粪便获得感染，CDC 曾将鹦鹉热衣原体列为 B 类生物防御剂。这些衣原体诱导的或相关的病理很大程度上是由于衣原体在真核细胞的细胞质液泡内有效复制或实现长期持续存在的能力，这得益于衣原体独特的细胞内双相生命周期和衣原体的能力躲避宿主防御。目前的提议旨在了解衣原体如何逃避非常重要的宿主防御效应机制——细胞凋亡。我们之前已经证明，衣原体具有有效的抗凋亡活性，这可能有助于衣原体在受感染宿主中长期存活的能力。通过鉴定负责衣原体抗细胞凋亡活性的分子并了解抗细胞凋亡分子如何按照当前项目中提出的方式发挥作用，我们也许能够开发出阻断衣原体抗细胞凋亡活性并预防衣原体细胞凋亡的试剂/方法。衣原体引起的病理。