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Mechanisms of Host Cell Infection by Chlamydia

衣原体感染宿主细胞的机制

基本信息

批准号：
8839177
负责人：
Richard S Stephens
金额：
$ 38.38万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-05-04 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8839177
关键词：
Activities of Daily Living Antibodies Binding Biochemical Cell Communication Cell Line Cell Surface Proteins Cell surface Cells Characteristics Chemicals Chinese Hamster Ovary Cell Chlamydia Chlamydia Infections Complex Comprehension Cysteine Data Development Diphtheria Toxin Disulfides Experimental Designs Eye Future Genes Genetic Genetic screening method Goals Growth Human Immune Immune Targeting Infection Intervention Isomerase Gene Knowledge Ligands Local Microbicides Mammalian Cell Maps Mediating Medical Membrane Membrane Proteins Methodology Microbiology Modeling Modification Molecular Monitor Mus Organism Outcome Study Oxidoreductase Pathogenesis Pathogenicity Post-Translational Protein Processing Process Protein Disulfide Isomerase Proteins Public Health Recombinant Proteins Recombinants Research Resistance Role Sexually Transmitted Diseases Sulfhydryl Compounds Surface System Techniques Testing Tissues Toxin Transfection Tropism Vaccine Design Vacuole Virulence Virus base chemical reduction clinical application design disulfide bond extracellular human disease in vivo inhibitor/antagonist innovation microbial microbial host neglect novel novel strategies pathogen protein aminoacid sequence protein complex public health relevance receptor scaffold suicide substrates transmission process uptake

项目摘要

DESCRIPTION (provided by applicant): Chlamydia is the most common cause of sexually transmitted diseases in the USA. As a reportable bacterial pathogen it is a significant medical and public health problem. Chlamydia strains that infect the eye are recognized as one of the seven great neglected diseases of humans. The long-term objectives are to understand the requirements for chlamydial infection of mammalian host cells. This will yield important fundamental information for the development of new approaches for intervention. Like viruses, Chlamydia must infect a mammalian cell to enable their growth and transmission. Thus, delineating the steps in the infection process is fundamental to understanding pathogenesis and virulence and providing new directions for medical treatment and public health control. The infection process is complex and involves cell invasion and subsequent growth and exit mechanisms. The focus of this application is on the first steps of cell infection- microbial attachment and entry. The hypothesis is that host cell surface proteins serve as receptors for chlamydial attachment and this interaction results in protein modifications that trigger entry of the organisms into their host cells. The specific aims include the identification of host surface proteins that are required for Chlamydia attachment and the substrate proteins required for chlamydial entry. The experimental design employs a unique and strong genetic platform for analyzing functional interactions between host cells and chlamydial organisms and also the application of robust biochemical approaches for monitoring and testing disulfide interactions in complex systems. The expected outcome of these studies is the identification of cellular surface components that are necessary for the attachment and uptake processes of chlamydial infection.

描述（由申请人提供）：衣原体是美国性传播疾病最常见的原因。作为一种可报告的细菌病原体，它是一个重大的医学和公共卫生问题。感染眼睛的衣原体菌株被认为是人类七大被忽视的疾病之一。长期目标是了解哺乳动物宿主细胞衣原体感染的要求。这将为制定新的干预办法提供重要的基本信息。像病毒一样，衣原体必须感染哺乳动物细胞才能生长和传播。因此，描述感染过程中的步骤对于了解致病机理和毒力以及为医疗和公共卫生控制提供新的方向至关重要。感染过程是复杂的，涉及细胞入侵和随后的生长和退出机制。该应用的重点是细胞感染的第一步-微生物附着和进入。假设宿主细胞表面蛋白质作为衣原体附着的受体，这种相互作用导致蛋白质修饰，触发生物体进入其宿主细胞。具体目标包括鉴定衣原体附着所需的宿主表面蛋白和衣原体进入所需的底物蛋白。实验设计采用了一个独特而强大的遗传平台，用于分析宿主细胞和衣原体生物之间的功能相互作用，以及应用稳健的生化方法来监测和测试复杂系统中的二硫键相互作用。这些研究的预期结果是确定衣原体感染的附着和摄取过程所必需的细胞表面成分。