The role of tick gut microbiota in Borrelia burgdorferi transmission to mice

摘要 该提案将描述蜱肠道微生物群对疏螺旋体能力的影响， 莱姆病病原体，即伯氏莱姆病病原体，从蜱传播到脊椎动物宿主。我们 最近的工作（Narasimhan等人，Cell Host Microbe 15：58 - 71，2014）证明蜱肠道微生物群 调节B。肩胛硬蜱的布氏定殖。我们的初步数据显示， 肠道微生物群促进有效B。Burgdorferi传播到哺乳动物宿主。这是一 人类莱姆病背景下的关键事件，并了解蜱肠道微生物群如何影响 将疏螺旋体传播给哺乳动物宿主将揭示预防莱姆病传播的新方法。 在目标1中，我们将表征和确定与以下相关的蜱肠道细菌谱： 降低B。伯氏螺旋体传播到脊椎动物宿主。此外，我们还将开始评估 从康涅狄格州流行地区获得的若虫蜱的微生物组成， 对实验室饲养的蜱虫的观察。在今后的实地研究中应用这些知识， 提供特定地理区域传播风险的新预测因子/生物标志物。 在目标2中，我们将对蜱肠道进行转录组分析，以描述 在B期间受肠道微生物群影响的蜱虫途径。伯氏传播与 重点关注多达10个被肠道微生物群显著改变的基因，我们将确定它们的功能 B上的结果。伯氏传播削弱疏螺旋体传播的潜在疫苗靶点 可以从这个功能分析中识别出来。 最后，我们将确定生态失调是否可能调节疏螺旋体毒力的表达谱 基因，并且另外影响螺旋体向宿主的传播。我们将重点关注脂蛋白 编码B的毒力基因。burgdorferi和解开一个新的理解如何B。burgdorferi 感知蜱肠道环境以调节毒力基因的表达。 这项研究工作将使该领域超越对蜱肠道微生物群的描述性理解， 并揭示了蜱肠道细菌对蜱-病原体相互作用的影响的机理 特别是关于病媒-病原体相互作用。蜱肠道微生物群提供了一种新的 了解B生物学的有利位置。伯氏螺旋体传播到小鼠和发展 新的范式来探索导致莱姆病传播的因素。

ABSTRACT This proposal will characterize the influence of tick gut microbiota on the ability of Borrelia burgdorferi, the Lyme disease agent, to be transmitted from ticks to the vertebrate host. Our recent work (Narasimhan et al, Cell Host Microbe 15:58-71, 2014) demonstrated that tick gut microbiota modulate B. burgdorferi colonization of Ixodes scapularis. Our preliminary data suggest that normal gut microbiota facilitate efficient B. burgdorferi transmission to the mammalian host. This is a critical event in the context of human Lyme disease and understanding how tick gut microbiota influence Borrelia transmission to the mammalian host will reveal new ways to prevent Lyme disease transmission. In Aim 1 we will characterize and determine tick gut bacterial profiles that are associated with decreased B. burgdorferi transmission to the vertebrate host. Further, we will also begin to assess the microbial compositions of nymphal ticks obtained from endemic regions in Connecticut to co-relate our observations on lab-reared ticks. Application of this knowledge to field studies in future efforts might provide new predictors/biomarkers of transmission risk in specific geographic areas. In Aim 2 we will perform a transcriptome analysis of the tick gut to describe the molecular pathways of the tick that are influenced by gut microbiota during B. burgdorferi transmission. With a focus on up to 10 genes that are significantly altered by gut microbiota we will determine their functional consequence on B. burgdorferi transmission. Potential vaccine targets to impair Borrelia transmission may be identified from this functional analysis. Finally, we will determine if dysbiosis might modulate the expression profiles of Borrelial virulence genes, and additionally influence spirochete transmission to the host. We will focus on the lipoprotein encoding virulence genes of B. burgdorferi and unravel a new understanding of how B. burgdorferi senses the tick gut environment to regulate the expression of virulence genes. This research effort will move the field beyond a descriptive understanding of tick gut microbiota, and unfold a mechanistic understanding of the influence of tick gut bacteria on tick-pathogen interactions in particular, and on vector-pathogen interactions in general. Tick gut microbiota provides a new vantage point to understand the biology of B. burgdorferi transmission to mice and to develop new paradigms to explore the factors that contribute to the spread of Lyme disease.