Chlamydial Manipulation of Host Apoptosis

描述（由申请人提供）：——衣原体控制宿主细胞凋亡的机制——人类衣原体感染在发展中国家和发达国家都是一个主要的健康问题。感染沙眼衣原体的泌尿生殖道感染是性传播细菌疾病的主要原因，也与某些类型的宫颈癌有关，而感染肺炎衣原体的呼吸道感染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。尽管鹦鹉螺杆菌主要是一种动物病原体，但人类也容易感染鹦鹉螺杆菌，从而患上危及生命的肺炎。由于人类可以通过被鹦鹉螺杆菌污染的动物粪便雾化感染鹦鹉螺杆菌，CDC曾将鹦鹉螺杆菌列为B类生物防御剂。这些衣原体诱导或相关的病理主要是由于衣原体在真核细胞的细胞质液泡内进行有效复制或实现长期持续的能力，这是由衣原体独特的细胞内双相生命周期和衣原体逃避宿主防御的能力所辅助的。目前的建议旨在了解衣原体如何逃避一个非常重要的宿主防御效应机制-细胞凋亡。我们先前已经证明衣原体具有强大的抗凋亡活性，这可能有助于衣原体在感染宿主中长时间存活的能力。通过识别负责衣原体抗凋亡活性的分子，并了解抗凋亡分子如何工作，我们可能能够开发出阻断衣原体抗凋亡活性和预防衣原体诱导病理的试剂/方法。

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.