Borella Gene Products Critical For Natural Infection Cycle

描述（由申请方提供）：莱姆病是一种在美国、欧洲和亚洲部分地区流行的病媒传播疾病，由细菌病原体伯氏疏螺旋体感染引起。尽管进行了几十年的深入研究，病原体生物学和感染的许多基本方面仍然在很大程度上未知。B。伯氏菌感染很难诊断，目前还没有预防人类疾病的疫苗。该申请将研究一组独特的疏螺旋体基因产物BB 0323，BBA 52和BBA 57，在螺旋体感染周期中发挥重要作用，如何有助于微生物生物学和发病机制的特定方面，并评估其作为莱姆病疫苗的潜在效用。我们有四个主要目标。首先，我们将研究B的一个关键毒力决定因子。在Burgdorferi中，BB 0323经历两步蛋白水解加工，最终产生不同的N-和C-末端多肽，其在细胞分裂和感染性中发挥特定作用。 其次，我们发现BBA 52对于病原体从蜱传播到小鼠至关重要，并且该蛋白质与蜱中的受体结合。我们建议研究BBA 52在媒介-病原体相互作用中的潜在功能及其在B中的作用。burgdorferi持久性和通过蜱传播。第三，我们表明，BBA 57，疏螺旋体基因产物的重要性，早期螺旋体感染小鼠，是一个主要的触发莱姆病关节炎。我们的研究会详细分析 BBA 57如何触发宿主炎症反应并促进螺旋体感染的分子和细胞机制。最后，本研究将探索莱姆病新疫苗候选物的鉴定以及基于新城堡病病毒（NDV）载体的免疫策略。由于NDV在人类中似乎是安全的，并且目前用于癌症患者的治疗性治疗，因此拟议的研究将为其作为抗人类莱姆病的可能疫苗载体的实用性奠定基础。总之，这些研究将有助于理解有趣的生物学和传染性的B。burgdorferi和hel开发了新的预防和治疗措施来对抗感染。

DESCRIPTION (provided by applicant): Lyme borreliosis is a prevalent vector-borne disease in the United States, Europe, and parts of Asia, caused the infection with the bacterial pathogen Borrelia burgdorferi. Despite several decades of intense studies, many fundamental aspects of pathogen biology and infection remain largely unknown. B. burgdorferi infection can be difficult to diagnose, and a vaccine to prevent disease in humans is currently unavailable. The application will study how a select set of unique borrelial gene-products BB0323, BBA52 and BBA57, that play important roles in the spirochete infection cycle, contribute to specific aspects of microbial biology and pathogenesis and also assess their potential utility as Lyme disease vaccines. We have four major goals. First, we will examine how a critical virulence determinant of B. burgdorferi, BB0323 undergoes two-step proteolytic processing that ultimately produce distinct N- and C-terminal polypeptides, which play specific roles in cell fission and infectivity. Second, we have discovered that BBA52 is critical for pathogen transmission from ticks to mice and that the protein binds to a receptor in ticks. We propose to study a potential function of BBA52 in vector-pathogen interaction and its role in B. burgdorferi persistence and transmission through ticks. Third, we show that BBA57, a borrelial gene-product important for early spirochete infection in mice, is a major trigger of Lyme arthritis. Our studies will dissect detail molecular and cellular mechanisms of how BBA57 triggers host inflammatory responses and also facilitates spirochete infection. Finally, the proposed study will explore the identification f new vaccine candidates as well as New castle disease virus (NDV) vector-based immunization strategies against Lyme disease. As NDV appears to be safe in humans and is currently in use for therapeutic treatment of cancer patients, the proposed study will establish a foundation for it utility as a possible vaccine vector against human Lyme disease. In sum, these studies will contribute to the understanding of the intriguing biology and infectivity of B. burgdorferi and hel develop novel preventive and therapeutic measures to combat infection.