Characterization of the Brucella abortus virB locus

流产布鲁氏菌 virB 基因座的表征

基本信息

项目摘要

DESCRIPTION (provided by applicant): Brucella abortus is a facultative intracellular pathogen that is highly infectious by the aerosol route and causes chronic, debilitating disease. A key step in B. abortus infection is the establishment of persistent infection within macrophages. The bacterial genes encoding virulence mechanisms required for specific interactions between Brucella and the macrophage remain largely undiscovered. We have identified a genetic locus of B. abortus, virB, that is required for establishing infection both in macrophages and In the mouse model. The B. abortus virB locus is predicted by sequence homology to encode a type IV secretion system. Our long- range goal is to elucidate the mechanism by which the virB locus mediates intracellular survival and persistent infection. The objective of this application is to study the expression of the virB genes and compare the interaction of wild type B. abortus and virB mutants with regard to vacuolar trafficking in the macrophage. The central hypothesis of this application is that the virB locus mediates a critical interaction with the macrophage that allows B. abortus to establish infection. The rationale for the proposed research is that characterization of B. abortus virulence factors mediating specific interactions with macrophages will form the basis for new approaches to treat or prevent brucellosis. We are uniquely prepared to undertake the proposed research, because we have generated tools for studying virB expression at both the transcriptional and translational level. Furthermore, the work will be performed in an excellent research environment that is conducive to its completion. Our Department contains several funded investigators working on intracellular bacterial pathogens and excellent BL-3 facilities, as well as other shared resources available for the study of host/pathogen interactions. The central hypothesis will be tested, and the objectives of this application accomplished by pursuing the following two specific aims: (1) Identify conditions for In vitro and in vivo expression of the B. abortus virB locus and localize protein products in the bacterium, and (2) Determine the mechanism by which the virB locus enables B. abortus to survive and grow intracellularly within macrophages. We expect that the results of this work will provide the first direct evidence for expression of the B. abortus virB proteins as well as define the environmental signals that induce expression of this locus. Furthermore, our results will provide information essential to defining the cellular interaction mediated by the virB locus. These results will be significant, because they are expected to provide new targets for preventive or therapeutic interventions to be employed in the case of illegitimate use of this bacterial pathogen. In addition, it is expected that these results will advance our knowledge of type IV secretion systems, which are used by a number of different bacterial pathogens to subvert the host's defense mechanisms.
描述(申请人提供):流产布氏杆菌是一种兼性 通过气溶胶途径高度传染的细胞内病原体, 会导致慢性衰弱性疾病B中的关键一步。流产感染是 巨噬细胞内持续感染的建立。细菌 基因编码的毒力机制所需的特定相互作用之间 布鲁氏菌和巨噬细胞在很大程度上仍未被发现。我们已经确定了一 B的遗传位点。流产病毒,virB,建立感染所需的病毒 在巨噬细胞和小鼠模型中。B。流产病毒B基因座是 通过序列同源性预测编码IV型分泌系统。我们长久以来- 范围目标是阐明virB基因座介导 细胞内存活和持续感染。的目的 应用是研究virB基因的表达,并比较 野生型B相互作用。关于空泡的abortus和virB突变体 巨噬细胞的运输本申请的中心假设是 virB基因座介导与巨噬细胞的关键相互作用, 允许B。流产以建立感染。建议的理由 研究是B表征。流产毒力因子介导 与巨噬细胞的特异性相互作用将成为新方法的基础 治疗或预防布鲁氏菌病。我们已做好准备, 我们提出了研究,因为我们已经生成了研究virB的工具, 在转录和翻译水平表达。此外,委员会认为, 这项工作将在一个良好的研究环境中进行, 有利于其完成。我们的部门有几个资助的 研究细胞内细菌病原体和优秀BL-3 设施,以及其他可供研究的共享资源 宿主/病原体相互作用中心假设将得到检验, 本申请的目的通过追求以下两个目标来实现 具体目的:(1)确定体外和体内表达 B。流产病毒B基因座并定位细菌中的蛋白质产物,和 (2)确定virB基因座启动B的机制。流产 在巨噬细胞内细胞内存活和生长。我们预计 这项工作的结果将提供第一个直接证据, B。流产病毒B蛋白以及定义环境信号, 诱导该基因座表达。此外,我们的研究结果将提供 定义由细胞因子介导的细胞相互作用所必需的信息 virB基因座。这些结果将是重要的,因为预计它们将 为预防或治疗干预提供新的目标 非法使用这种细菌病原体的情况下。此外还 我希望这些结果将推进我们对IV型分泌的认识 系统,这些系统被许多不同的细菌病原体使用, 破坏宿主的防御机制

项目成果

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Renee M Tsolis其他文献

Renee M Tsolis的其他文献

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{{ truncateString('Renee M Tsolis', 18)}}的其他基金

2023 Salmonella Biology and Pathogenesis Gordon Research Conference and Seminar
2023年沙门氏菌生物学与发病机制戈登研究会议暨研讨会
  • 批准号:
    10683617
  • 财政年份:
    2023
  • 资助金额:
    $ 20万
  • 项目类别:
Neutrophil-intrinsic role of SLC11A1/NRAMP1 in control of bacterial infection
SLC11A1/NRAMP1 在控制细菌感染中的中性粒细胞内在作用
  • 批准号:
    10468025
  • 财政年份:
    2019
  • 资助金额:
    $ 20万
  • 项目类别:
Neutrophil-intrinsic role of SLC11A1/NRAMP1 in control of bacterial infection
SLC11A1/NRAMP1 在控制细菌感染中的中性粒细胞内在作用
  • 批准号:
    10224776
  • 财政年份:
    2019
  • 资助金额:
    $ 20万
  • 项目类别:
Neutrophil-intrinsic role of SLC11A1/NRAMP1 in control of bacterial infection
SLC11A1/NRAMP1 在控制细菌感染中的中性粒细胞内在作用
  • 批准号:
    10022095
  • 财政年份:
    2019
  • 资助金额:
    $ 20万
  • 项目类别:
2019 Microbial Adhesion and Signal Transduction GRC/GRS
2019微生物粘附与信号转导GRC/GRS
  • 批准号:
    9752745
  • 财政年份:
    2019
  • 资助金额:
    $ 20万
  • 项目类别:
Neutrophil-intrinsic role of SLC11A1/NRAMP1 in control of bacterial infection
SLC11A1/NRAMP1 在控制细菌感染中的中性粒细胞内在作用
  • 批准号:
    10683118
  • 财政年份:
    2019
  • 资助金额:
    $ 20万
  • 项目类别:
Neutrophil-intrinsic role of SLC11A1/NRAMP1 in control of bacterial infection
SLC11A1/NRAMP1 在控制细菌感染中的中性粒细胞内在作用
  • 批准号:
    10772361
  • 财政年份:
    2019
  • 资助金额:
    $ 20万
  • 项目类别:
Neutrophil-intrinsic role of SLC11A1/NRAMP1 in control of bacterial infection
SLC11A1/NRAMP1 在控制细菌感染中的中性粒细胞内在作用
  • 批准号:
    10755395
  • 财政年份:
    2019
  • 资助金额:
    $ 20万
  • 项目类别:
Systemic infections with non-typhoidal Salmonella
非伤寒沙门氏菌全身感染
  • 批准号:
    9238432
  • 财政年份:
    2016
  • 资助金额:
    $ 20万
  • 项目类别:
Detection of bacterial Type IV secretion by the unfolded protein response
通过未折叠蛋白反应检测细菌 IV 型分泌物
  • 批准号:
    8718850
  • 财政年份:
    2014
  • 资助金额:
    $ 20万
  • 项目类别:
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