Mechanisms of Host Cell Infection by Chlamydia

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。 公共卫生相关性：相关性是为了了解衣原体感染机制，以制定创新的干预方法。与细胞表面蛋白相互作用的衣原体配体是免疫干预或感染性连续步骤所需步骤的抑制剂的靶标。例如，知识的要求和目标的蛋白质巯基还原可能有未来的临床应用，为衣原体适合作为局部杀微生物剂的自杀底物的发展。

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. PUBLIC HEALTH RELEVANCE: The relevance is to gain an understanding of chlamydial infection mechanisms for the development of innovative approaches for intervention. The chlamydial ligand that interacts with cell surface proteins is a target for immune intervention or for inhibitors of steps required for successive steps in infectivity. For example, knowledge of the requirement and target for protein thiol reduction may have future clinical application for the development of suicide substrates for chlamydiae suitable as topical microbicides.