Role of Borrelia burgdorferi Rev fibronectin binding proteins in Lyme disease

伯氏疏螺旋体 Rev 纤连蛋白结合蛋白在莱姆病中的作用

基本信息

批准号：
8318658
负责人：
Catherine Ayn Brissette
金额：
$ 10.8万
依托单位：
UNIVERSITY OF NORTH DAKOTA
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：
2011-08-15 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8318658
关键词：
Address Arthritis Arthropods Bacterial Adhesins Binding Binding Proteins Bite Borrelia Borrelia burgdorferi Cardiac Clinical Connective Tissue Development Diagnostic Disease Exanthema Extracellular Matrix Fibronectins Foundations Gene Expression Human Immune system Infection Ixodes Knowledge Ligands Lyme Disease Membrane Proteins Molecular Names Neurologic Outcome Pathogenesis Pathway interactions Process Production Property Protein Binding Proteins Regulation Reporting Research Role Staging Symptoms Testing Ticks Time Tissues United States Virulence extracellular flu improved insight mutant novel novel therapeutics pathogen post-doctoral training protein B public health relevance vector

Address Arthritis Arthropods Bacterial Adhesins Binding Binding Proteins Bite Borrelia Borrelia burgdorferi Cardiac Clinical Connective Tissue Development Diagnostic Disease Exanthema Extracellular Matrix Fibronectins Foundations Gene Expression Human Immune system Infection Ixodes Knowledge Ligands Lyme Disease Membrane Proteins Molecular Names Neurologic Outcome Pathogenesis Pathway interactions Process Production Property Protein Binding Proteins Regulation Reporting Research Role Staging Symptoms Testing Ticks Time Tissues United States Virulence extracellular flu improved insight mutant novel novel therapeutics pathogen post-doctoral training protein B public health relevance vector

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项目摘要

DESCRIPTION (provided by applicant): Borrelia burgdorferi, the Lyme disease agent, is an extracellular pathogen that must adapt to both its tick vector and its vertebrate hosts. B. burgdorferi causes persistent infection that can last for the hosts' lifetime. The pathogenesis of B. burgdorferi depends on outer surface proteins that interact with the cells, extracellular matrix, and components of the hosts' immune system. I recently identified two novel fibronectin-binding proteins in B. burgdorferi named RevA and RevB. Both of these bacterial surface proteins are expressed during mammalian infection, yet repressed during colonization of vector ticks. I hypothesize that these unique fibronectin binding proteins are critical to the natural infectious cycle by helping B. burgdorferi interact with host tissues. I propose three Specific Aims: (1) analyze the roles of RevA and RevB during the B. burgdorferi infectious cycle; (2) define the mechanisms involved in RevA and RevB binding to fibronectin; (3) detail the mechanisms by which B. burgdorferi controls production of RevA and RevB. Knowledge gained from these studies will form the foundation for an R01 aimed at understanding how fibronectin-binding proteins contribute to B. burgdorferi virulence, thereby directing the development of novel therapeutic and preventative treatments for Lyme disease. Public Health Relevance: The Lyme disease agent, Borrelia burgdorferi, can infect humans for long periods of time and is frequently found associated with host connective tissues, and I identified two novel B. burgdorferi proteins that bind host fibronectin, a major component of host extracellular matrix (ECM). I hypothesize that fibronectin-binding proteins help B. burgdorferi interact with host tissues and are crucial for mammalian infection. The proposed studies will critically test this hypothesis, by examining the role(s) of fibronectin-binding proteins in B. burgdorferi infection processes, defining the mechanisms by which the borrelial proteins bind to their host ligand, and examining how the Lyme disease spirochete controls expression of these adhesins.

描述（由申请人提供）：莱姆病剂Borrelia Burgdorferi是一种细胞外病原体，必须适应其tick载体及其脊椎动物宿主。 B. Burgdorferi会导致持续的感染，可以持续到宿主的一生。 B. burgdorferi的发病机理取决于与细胞相互作用的外表面蛋白，细胞外基质和宿主免疫系统的成分。我最近在B. burgdorferi中确定了两种新型的纤连蛋白结合蛋白，名为Reva和RevB。这两种细菌表面蛋白在哺乳动物感染过程中均表达，但在载体壁虱定植期间受到抑制。我假设这些独特的纤连蛋白结合蛋白通过帮助B. burgdorferi与宿主组织相互作用，对自然感染周期至关重要。我提出了三个特定的目的：（1）分析B. burgdorferi感染周期中Reva和Revb的作用；（2）定义Reva和Revb与纤连蛋白结合的机制；（3）详细说明B. Burgdorferi控制Reva和RevB的生产的机制。从这些研究中获得的知识将构成R01的基础，旨在了解纤连蛋白结合蛋白如何促进爆发芽孢杆菌的毒力，从而指导莱姆病的新型治疗和预防性治疗的发展。公共卫生相关性：莱姆病剂，疏螺旋体Burgdorferi，可以长时间感染人类，并且经常发现与宿主结缔组织相关，我发现了两种新型的B. burgdorferi蛋白，它们结合宿主纤维蛋白（宿主纤连蛋白），宿主纤连蛋白是宿主外基质的主要成分（ECM）的主要成分。我假设纤连纤维蛋白结合蛋白有助于B. burgdorferi与宿主组织相互作用，并且对于哺乳动物感染至关重要。拟议的研究将通过检查纤连蛋白结合蛋白在伯氏芽孢杆菌感染过程中的作用，从而批判性地检验该假设，从而定义了骨蛋白与宿主配体结合的机制，并检查莱姆病疾病如何控制这些粘附素的表达。