Chlamydial Manipulation of Host Apoptosis

衣原体调控宿主细胞凋亡的机制 衣原体感染在人类中造成了一个严重的健康问题， 发达国家。泌尿生殖道沙眼衣原体感染是 性传播细菌疾病，也与某些类型的宫颈癌有关，而 肺炎衣原体呼吸道感染与动脉粥样硬化有关，动脉粥样硬化是一种主要的 心脑疾病致死的血管状况。尽管鹦鹉螺这个物种主要是一种动物 病原体，人类也容易感染鹦鹉热弧菌，发展成威胁生命的 肺炎。因为人类可以通过被污染的雾化动物粪便感染 美国疾病控制与预防中心曾将鹦鹉弧菌列为B类生物防御制剂。 这些衣原体引起的或与之相关的病理在很大程度上是由于衣原体能够 在细胞质液泡中高效地复制或实现长期存留 真核细胞，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。目前的提案旨在理解如何 衣原体逃避一种非常重要的宿主防御效应机制，即细胞凋亡。我们有 先前证明衣原体具有很强的抗细胞凋亡活性，这可能 有助于衣原体在受感染的宿主中长时间存活。通过 衣原体抗凋亡活性相关分子(S)的鉴定与认识 抗凋亡分子是如何发挥作用的，正如当前项目中提出的，我们或许能够 开发阻断衣原体抗细胞凋亡活性和预防的试剂/方法 衣原体引起的病理。

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 antiapoptotic 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 antiapoptotic activity and understanding how the antiapoptotic molecules work as proposed in the current project, we may be able to develop reagents/approaches for blocking the Chlamydial antiapoptotic activity and preventing chlamydia-induced pathologies.