Borrelia gene products critical for natural infection cycle

6.项目总结/摘要 为了确定莱姆病预防的新治疗靶点，我们建议分析以下因素的作用： 在蜱中高度诱导的伯氏疏螺旋体基因产物。B。burgdorferi在自然界中蓬勃发展， 涉及小型啮齿动物和硬蜱的复杂的地方流行病循环。未成熟的蜱虫从一个 感染宿主，跨时空维持B。burgdorferi，并在随后的血液中将其传播给幼稚宿主 餐我们假设，在微生物的特定阶段优先被诱导的螺旋体基因， 蜱的生命周期对于维持病原体在自然界中的存在很重要。这些蜱虫感染的螺旋体 蛋白质也可以暴露在病原体表面上，B。Burgdorferi传播应受到以下因素的影响： 针对它们的特异性抗体。我们将使用模型B来开发这个范例。伯氏菌基因BB 0323， bba 0246、bba 62和bba 52，其中许多位于螺旋体表面，并在 在特定的时间和特定的组织中。首先，我们将探讨靶向诱变的效果， 基因对螺旋体的生命周期，以建立特定的B的相对重要性。burgdorferi基因产物 并为随后的抗体阻断研究鉴定潜在的靶点。我们将重点关注重要的 螺旋体基因，并评估抗体是否针对所选的B。burgdorferi基因产物中断了 微生物的生命周期，并导致宿主免疫保护。我们还将评估蜱虫诱导的 螺旋体蛋白质集中在载体-病原体相互作用。这些信息将有助于澄清适应性 细菌的策略，坚持在不同的主机和载体组织阵列，并可能有助于新的 制定预防措施以破坏螺旋体生命周期的目标。

6. Project Summary/Abstract To identify new therapeutic targets for Lyme disease prevention, we propose to analyze the roles of Borrelia burgdorferi gene products that are highly induced in ticks. B. burgdorferi thrives in nature through an intricate enzootic cycle involving small rodents and Ixodes ticks. Immature ticks acquire the pathogen from an infected host, transstadially maintain B. burgdorferi, and transmit it to na¿ve hosts during a subsequent blood meal. We hypothesize that spirochete genes that are preferentially induced at specific stages of the microbial life cycle in ticks are important for sustaining the pathogen in nature. As many of these tick-induced spirochete proteins may also be exposed on the pathogen surface, B. burgdorferi transmission should be influenced by specific antibodies against them. We will develop this paradigm using the model B. burgdorferi genes bb0323, bb0246, bba62 and bba52, many of which are localized on the spirochete surface and are upregulated at specific times and in specific tissues in ticks. First, we will explore the effect of targeted mutagenesis of the genes on the spirochete life cycle to establish the relative importance of specific B. burgdorferi gene products and to identify potential targets for subsequent antibody-blocking studies. We will then focus on important spirochete genes and assess if antibodies directed against selected B. burgdorferi gene products interrupt the microbial life cycle and result in host immunoprotection. We will also assess functions of tick-induced spirochete proteins focusing on vector-pathogen interaction. The information will help clarify the adaptive strategies of a bacterium that persists in a diverse array of host and vector tissues, and may contribute new targets for the development of preventive measures for disruption of the spirochete life cycle.