DbpA/B proteins of Borrelia burgdorferi & Lyme arthritis

伯氏疏螺旋体的 DbpA/B 蛋白

• 批准号: 7088295
• 负责人: Nikhat Parveen
• 金额: $ 7.78万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 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 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7088295
• 关键词: Borrelia; Lyme disease; adhesin; arthritis; bacteria infection mechanism; bacterial proteins; decorin; disease /disorder model; infectious arthritis; 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）：莱姆病是一种独特的临床系统，用于研究慢性炎症性疾病的细胞和分子机制。这种由伯氏疏螺旋体螺旋体引起的疾病是美国最流行的节肢动物传播疾病。它是一种多系统疾病，影响皮肤，肌肉，关节，心脏和神经系统。如果不治疗，慢性表现是经常观察到的，莱姆关节炎是北美最常见的症状。我的长期目标是确定B的毒力因子。本研究对莱姆病的致病机理进行了初步探讨，并对莱姆病的致病机理、诊断和预防进行了初步探讨。糖胺聚糖（GAG），普遍表达在所有有核细胞的表面上，被各种莱姆病螺旋体识别，并且几种细菌分子参与这种粘附。核心蛋白聚糖结合脂蛋白DbpA和B的Dbp B。除了蛋白聚糖核心蛋白聚糖外，伯氏螺旋体还显示出对肝素和硫酸皮肤素GAG的亲和力。我的假设是DbpA和Dbp B有助于B在各种组织中的定殖。在一些实施方案中，所述的抗病毒抗体与存在于宿主细胞上的GAG和核心蛋白聚糖结合，并引发皮肤和关节中的炎症反应，引起游走性红斑和莱姆关节炎。 本研究的主要问题是：（1）DbpA和Dbp B是否参与了GAG介导的B的粘附。对宿主细胞和易感小鼠关节中的炎症反应的影响？(2)dbpA和dbp B基因的缺失是否影响B的附着。对宿主细胞有什么影响(3)DbpA和Dbp B脂蛋白是B的重要毒力因子。引发莱姆关节炎的伯氏螺旋体感染吗症状：莱姆关节炎表现出与类风湿性关节炎相似的几种症状。然而，与类风湿性关节炎不同，莱姆病的致病因子是已知的，因此，分析这种破坏性关节炎形式所涉及的分子机制是可行的。此外，B.感染小鼠表现出与人类莱姆病相似的症状，因此，小鼠模型为分析莱姆病的机制提供了理想的系统。本研究将描述两种螺旋体脂蛋白粘附素在小鼠莱姆关节炎模型中的作用。