Rrp2, an atypical bacterial enhancer binding protein in Borrelia burgdorferi

Rrp2，伯氏疏螺旋体中的非典型细菌增强子结合蛋白

• 批准号: 9230812
• 负责人: Zhiming Ouyang
• 金额: $ 2.58万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2017-08-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9230812
• 关键词: Accounting; Amino Acids; Arthropod Vectors; Arthropods; Bacteria; Bacteria sigma factor KatF protein; Biology; Borrelia; Borrelia burgdorferi; Complex; Data; Development; Environment; Etiology; Future; Gene Expression; Genes; Genetic Transcription; Goals; Growth; In Vitro; Infection; Life Cycle Stages; Lyme Disease; Lyme Disease Vaccines; Mammals; Membrane Proteins; Modality; Molecular; Nature; Order Spirochaetales; Pathogenesis; Public Health; Research; Role; Ticks; Transcriptional Activation; United States; Virulence; antimicrobial; base; conditional mutant; disease transmission; enhancer binding protein; innovation; insight; novel; protein profiling; public health relevance; transcriptome; vector

 DESCRIPTION (provided by applicant): Borrelia burgdorferi, the etiological agent of Lyme disease, maintains itself in nature via a complex life cycle involving an arthropod (tick) vector and small mammals. During its cycle between ticks and mammals, B. burgdorferi alters its outer surface protein profiles to interact with and adapt to these two dramatically diverse niches. For a complete understanding of Lyme disease transmission and pathogenesis, it is of major importance to discern the molecular mechanisms of borrelial host adaptation. In this regard, we recently discovered that a putative bacterial enhancer binding protein (bEBP), Rrp2, is essential for B. burgdorferi to establish infection in mammalian hosts. More importantly, our preliminary data indicate that Rrp2, distinct from other classical bEBPs, is essential for borrelial growth in vitro. These data strongly implicate Rrp2 as an atypical bEBP. This proposal seeks to elucidate the molecular bases underlying Rrp2's surprising essentiality and its unconventional activity. In Specific Aim 1, we will assess the contributions of potential key amino acids to Rrp2's essentiality to gain initial insights into the structural basis of Rrp2's novel activity. In Specifc Aim 2, we shall identify new σ54/RpoS-independent factors influenced by Rrp2 by using global transcriptome analyses. These combined structural and functional studies will not only advance our understanding of regulatory control over borrelial virulence expression, but also account for a major paradigm-shift in our mechanistic understanding of bacterial σ54 biology.

 描述(申请人提供)：伯氏疏螺旋体是莱姆病的病原体，通过节肢动物(壁虱)媒介和小型哺乳动物的复杂生命周期维持自身在自然界中的生存。在扁虱和哺乳动物之间的循环中，伯氏杆菌改变了它的外表面蛋白质谱，以与这两个截然不同的生态位相互作用并适应它们。为. 全面了解莱姆病的传播和发病机制，对于弄清疏螺旋体宿主适应的分子机制具有重要意义。在这方面，我们最近发现一个假定的细菌增强子结合蛋白(BEBP)，RRP2，对于伯氏杆菌在哺乳动物宿主中建立感染是必不可少的。更重要的是，我们的初步数据表明，RRP2不同于其他经典的BEBP，对于体外生长是必不可少的。这些数据强烈暗示RRP2是一种非典型的bEBP。这一提议旨在阐明RRP2 S令人惊讶的重要性及其非常规活性背后的分子基础。在具体目标1中，我们将评估潜在的关键氨基酸对RRP2的S重要性的贡献，以获得对RRP2的S新奇活动的结构基础的初步见解。在特定的目标2中，我们将利用全球转录组分析来识别受σ2影响的新的RRP54/RPOS非依赖性因子。这些结构和功能相结合的研究不仅将促进我们对轮状病毒毒力表达的调控的理解，而且也将解释我们对细菌σ54生物学机制理解的重大范式转变。