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（由适用提供）：莱姆病的病因学药Borrelia Burgdorferi通过涉及节肢动物（TICK）载体和小型哺乳动物的复杂生命周期来保持自然界。在tick虫和哺乳动物之间的周期中，B。burgdorferi改变了其外表面蛋白质谱以与这两个巨大的壁nikes相互作用并适应这两个易变的壁ni。对于 完全了解莱姆病的传播和发病机理，辨别骨质宿主适应的分子机制至关重要。在这方面，我们最近发现，假定的细菌增强蛋白（BEBP）RRP2对于B. burgdorferi在哺乳动物宿主中建立感染至关重要。更重要的是，我们的初步数据表明RRP2与其他经典的BEBP不同，对于体外骨质生长至关重要。这些数据强烈暗示RRP2是非典型BEBP。该提案旨在阐明RRP2的惊喜重要性及其非常规活动的基础。在特定的目标1中，我们将评估潜在的关键氨基酸对RRP2的重要性的贡献，以获得对RRP2新活性的结构基础的初步见解。在特定目标2中，我们将通过使用全局转录组分析来确定受RRP2影响的新σ54/rpos独立因素。这些结合的结构和功能研究不仅会提高我们对对脊髓病毒表达的调节性控制的理解，而且还考虑了我们对细菌σ54生物学的机械理解时的主要范式转移。