The role of OspC in Borrelia pathogenesis

OspC 在疏螺旋体发病机制中的作用

• 批准号: 7650493
• 负责人: RICHARD T MARCONI
• 金额: $ 35.45万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-08 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7650493
• 关键词: Americas; Antigens; Arthropods; Blood; Borrelia; Borrelia burgdorferi; Centers for Disease Control and Prevention (U.S.); Development; Disease; Dissection; Europe; Gene Silencing; Health; Human; Incidence; Infection; Ingestion; Invasive; Investigation; Ligands; Lipoproteins; Lyme Disease; Mammals; Maps; Methodology; Molecular; Mutagenesis; Order Spirochaetales; OspC protein; Pathogenesis; Play; Prevention; Property; Reporting; Resolution; Role; Site; Structure; Surface; Tertiary Protein Structure; Testing; Ticks; United States; Virulence; Virulence Factors; enzootic; genetic manipulation; in vivo; mutant; pathogen; prevent; response; transmission process

Lyme disease, the leading arthropod borne disease in N. America and Europe, is caused by the spirochetes Borrelia burgdorferi, B. garinii and B. afzelii. As the endemic regions and incidence of Lyme disease increase, there is a pressing need to advance our understanding of molecular mechanisms of pathogenesis of its causative agents. Outer surface protein C (OspC) is an immmunodominant antigen that has been implicated as an important virulence factor. The precise role(s) of OspC in pathogenesis are not clearly defined and remains the subject of intensive investigation and debate. It has been proposed that OspC plays a critical role in the transmission process and or in the establishment of infection in the mammalian host. With the development of genetic manipulation methodologies for the Borrelia and the determination of high resolution crystal structures for OspC, it is now possible to utilize and exploit this information to identify the determinants of OspC that contribute to virulence and pathogenesis. In this application, unique approaches are proposed for identifying mammalian produced ligands for OspC, mapping its functional domains and determining which specific steps in the infectious cycle OspC participates in.le.

莱姆病是N.美国和欧洲， 由伯氏疏螺旋体（Borrelia burgdorferi）、B. garinii和B. afzelii。作为地方病 莱姆病的地区和发病率增加，迫切需要推进 我们对其致病因子发病机理的分子机制的理解。 外表面蛋白C（OspC）是一种免疫显性抗原， 被认为是重要的毒力因子。OspC在以下方面的确切作用 发病机制尚不清楚，仍是深入研究的主题 和辩论有人提出，OspC在传输中起着关键作用， 过程和/或在哺乳动物宿主中建立感染。与 开发用于疏螺旋体和 确定OspC的高分辨率晶体结构，现在可以利用 并利用这些信息来确定OspC的决定因素， 毒力和致病性。在本申请中，提出了独特的方法， 鉴定哺乳动物产生的OspC配体，定位其功能结构域， 确定OspC参与感染周期中的哪些具体步骤。