Chlamydial Manipulation of Host Apoptosis

衣原体操纵宿主细胞凋亡

基本信息

批准号：
6828399
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
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-07-01 至 2006-02-14
项目状态：
已结题

项目摘要

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.

宿主细胞凋亡的衣原体操纵机制人类的衣原体感染在发展和发达国家。泌尿生殖道被沙眼梭状芽孢杆菌感染是性传播细菌性疾病，也与某些类型的宫颈癌有关，而肺炎梭菌菌种的呼吸道感染与动脉粥样硬化有关，动脉粥样硬化是心脏症状死亡的主要血管疾病。尽管C. psittaci的物种主要是动物病原体，但人类也容易受到C. psittaci感染的影响，并患有威胁生命的肺炎。由于人类可以通过被c. psittaci生物污染的雾化动物粪便获得感染，因此疾病预防控制中心曾经将C. psittaci列为Biodefense的B类代理。这些衣原体诱导或相关的病理很大程度上是由于衣原体能力复制或在真核生物细胞的细胞质液泡内实现长期持久性，这得到了chlamydial独特的细胞内双皮亚生命周期和chlam症的疾病的侵害。当前的建议旨在了解衣原体如何逃避一种非常重要的宿主防御效应器机制---凋亡。我们以前已经证明，衣原体具有有效的抗凋亡活性，这可能有助于长期在感染宿主中生存的衣原体能力。通过识别负责衣原体抗凋亡活性的分子，并了解当前项目中提出的抗凋亡分子如何工作，我们可能能够开发试剂/方法来阻断衣原体的抗凋亡活性并预防chlamydia诱导的病理学。