DbpA/B proteins of Borrelia burgdorferi & Lyme arthritis

伯氏疏螺旋体的 DbpA/B 蛋白

• 批准号: 6708371
• 负责人: Nikhat Parveen
• 金额: $ 7.95万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6708371
• 关键词: Borrelia; Lyme disease; adhesin; arthritis; bacteria infection mechanism; bacterial proteins; decorin; disease /disorder model; inflammation; laboratory mouse; mucopolysaccharides; protein binding

DESCRIPTION (provided by applicant): Lyme disease presents a unique clinical system to study cellular and molecular mecahnisms responsible for chronic inflammatory diseases. The disease, caused by the spirochete Borrelia burgdorfen, is the most prevalent arthropod borne disease in the United States. It is a multisystemic illness that affects skin, muscles, joints, heart and nervous system. If left untreated, chronic manifestations are frequenctly observed and Lyme arthritis is the most common symptom in North America. My Iong term qoal is to identify the virulence factors of B. burgdorferi involved in attachment to host cells and in colonization of various tissues, and characterize their role in the pathogenesis, diagnosis and prevention of chronic Lyme disease. Glycosaminoglycans (GAGs), ubiquitously expressed on the surface of all nucleated cells, are recognized by various Lyme spirochetes and several bacterial molecules are involved in this adherence. Decorin binding lipoproteins DbpA and DbpB of B. burgdorferi show affinity for heparin and dermatan sulfate GAGs in addition to the proteoglycan decorin. My hypothesis is that DbpA and DbpB contribute to the colonization of various tissues by B. burgdorferi binding to GAGs and decorin present on the host cells and trigger an inflammatory response in skin and joints causing erythema migrans and Lyme arthritis. The major question to be addressed in this study are: (1) Do DbpA and DbpB contribute to the GAGsmediated attachment of B. burgdorferi to host cells and to the inflammatory response in the joints of susceptible mice? (2) Does deletion of dbpA and dbpB genes affect attachment of B. burgdorferi to the host cells? (3) Are DbpA and DbpB lipoproteins essential virulence factors of B. burgdorferi that trigger Lyme arthritis? Si,qniflcance: Lyme arthritis exhibits several symptoms similar to those of rheumatoid arthritis. However, unlike rheumatoid arthritis, the causative agent is known in Lyme disease and hence, it is feasible to analyze the molecular mechanisms involved in this form of destructive arthritis. In addition, B. burgdorfer/ infected mouse exhibits symptoms similar to those of human Lyme disease, and hence, murine model provides an ideal system to analyze the mechanisms of Lyme borreliosis. This study will characterize the role of two spirochete lipoprotein adhesins in Lyme arthritis in the murine model.

描述（由申请人提供）：莱姆病介绍了一种独特的临床系统，用于研究负责慢性炎症性疾病的细胞和分子麦克纳主义。这种疾病是由螺旋体玻璃体伯氏引起的，是美国最普遍的节肢动物传播疾病。这是一种多系统疾病，会影响皮肤，肌肉，关节，心脏和神经系统。如果未治疗，则经常观察到慢性表现，而莱姆关节炎是北美最常见的症状。我的离子术语QOAL是确定与宿主细胞附着和各种组织的定殖有关的爆发芽孢杆菌的毒力因子，并表征它们在发病机理，诊断和预防慢性莱姆病的作用。在所有成核细胞表面表达的普遍表达的糖胺聚糖（GAGS）均被各种莱姆螺旋体识别，并且几个细菌分子参与了这种粘附。 B. bugdorferi的Decorin绑定脂蛋白DBPA和DBPB除了蛋白聚糖Decorin外，还显示了对肝素和硫酸皮肤病的亲和力。我的假设是，DBPA和DBPB通过B. burgdorferi与存在于宿主细胞上的GAGS和Decorin结合的各种组织的定殖，并引发皮肤和关节引起炎症反应，并引起红斑偏头痛和莱姆关节炎。 在这项研究中要解决的主要问题是：（1）DBPA和DBPB是否有助于B. burgdorferi对宿主细胞的附着以及易感小鼠关节的炎症反应？ （2）DBPA和DBPB基因的删除会影响伯氏芽孢杆菌对宿主细胞的附着吗？ （3）DBPA和DBPB脂蛋白是否会触发莱姆关节炎的B. burgdorferi的必要毒力因子？ SI，Qniflcance：莱姆关节炎表现出与类风湿关节炎相似的几种症状。然而，与类风湿关节炎不同，病因在莱姆病中是已知的，因此可以分析与这种破坏性关节炎形式相关的分子机制。此外，B。B。Burgdorfer/受感染的小鼠表现出类似于人类莱姆病的症状，因此，Murine模型提供了一个理想的系统来分析莱姆毛促性病的机制。这项研究将表征鼠模型中两种螺旋体脂蛋白粘附素在莱姆关节炎中的作用。