The role of OspC in Borrelia pathogenesis

OspC 在疏螺旋体发病机制中的作用

• 批准号: 7826206
• 负责人: RICHARD T MARCONI
• 金额: $ 36.65万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7826206
• 关键词: Americas; Antigens; Arthropods; Borrelia; Borrelia burgdorferi; Development; Disease; Europe; Generations; Goals; Grant; Human; Incidence; Infection; Investigation; Ligand Binding; Ligands; Lyme Disease; Mammals; Maps; Methodology; Modification; Molecular; Order Spirochaetales; OspC protein; Outcome; Pathogenesis; Play; Property; Proteins; Resolution; Role; Series; Site; Structure; Ticks; Transgenic Organisms; Variant; Virulence; Virulence Factors; Work; base; citrate carrier; genetic manipulation; in vivo; limitin; mutant; research study; 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.

莱姆病是美国和欧洲的主要节肢动物传播疾病，是 由螺旋体Borrelia Burgdorferi，B。Garinii和B. afzelii引起的。作为流行 区域和莱姆病的发病率增加，需要推进 我们对其致病剂发病机理的分子机制的理解。 外表面蛋白C（OSPC）是一种免疫抑制抗原，已经 被视为重要的毒力因子。 OSPC的确切作用 发病机理并未明确定义，并且仍然是深入研究的主题 和辩论。有人提出，OSPC在传输中起着至关重要的作用 在哺乳动物宿主中建立感染的过程和 /或或或或在建立感染中。与 开发疏葡萄和的基因操纵方法 确定OSPC的高分辨率晶体结构，现在可以使用 并利用此信息来识别有助于的OSPC的决定因素 毒力和发病机理。在此应用中，提出了独特的方法 识别哺乳动物为OSPC产生的配体，绘制其功能域和 确定传染性周期OSPC中哪些特定步骤参与。