Intra- and inter species cell-cell communication in Vibrio cholerae
霍乱弧菌的种内和种间细胞通讯
基本信息
- 批准号:7329251
- 负责人:
- 金额:$ 4.68万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-09-01 至 2010-08-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAntibioticsArchitectureBacteriaCell CommunicationCellsChemicalsCholeraCommunicationComplexDetectionDevelopmentEnvironmentGene ExpressionGene Expression RegulationGene TargetingGoalsHumanIntestinesLaboratoriesLeadMeasurementMeasuresMethodologyMolecularOmpR proteinOutputPathway interactionsPopulation DensityProductionRegulatory ElementResearchRoleSignal PathwaySignal TransductionSignaling MoleculeSystemTranslatingVibrio choleraeVirulenceWaterWorkbeta-aspartyl phosphatedetectorextracellularfitnessin vivoinorganic phosphateinsightnovelpathogenquorum sensingresponse
项目摘要
DESCRIPTION (provided by applicant): The human pathogen Vibrio cholerae uses quorum sensing which involves the production, release, and subsequent detection of chemical signaling molecules called autoinducers, to regulate virulence gene expression in response to changes in cell-population density and species complexity. Two V. cholerae autoinducer-detection systems, one for intra-species and one for inter-species communication, are currently known. The long term goal of this application is to understand the molecular mechanisms underlying intra-species and inter-species quorum-sensing signaling in this bacterium. The unique information encoded in each extracellular autoinducer is translated internally into discrete levels of the phosphorylated response regulator LuxO, which determines the final output of the V. cholerae quorum-sensing system. Due to the instability of aspartyl phosphates, in vivo levels of phosphorylated bacterial response regulators have never been directly determined. To understand the signal-response input-output relationship in the V. cholerae quorum-sensing circuit, my first aim is to develop methodology for the quantitative measurement of phospho-LuxO levels in V. cholerae cells. Integration of the information contained in the two different autoinducers into a single regulatory network could allow the V. cholerae quorum-sensing system to function as a coincidence detector. Alternatively, this circuit may facilitate distinct gene regulation by any or all combinations of the two autoinducers. My second aim is focused on distinguishing between these two possibilities by investigating the effect of each autoinducer on specific target gene expression. Measurement of the temporal expression dynamics of selected target genes will be performed to establish whether the autoinducers function together or if there is an ordered gene expression hierarchy in response to different autoinducer combinations. Results from these studies will fully define the role of each regulatory element in the quorum-sensing signaling circuit. The third aim of this application is to identify novel chemical signal communication pathways that exist between V. cholerae and other bacterial species. Inter-species communication likely enables V. cholerae to adapt, compete, and survive in complex environments such as contaminated water and the human intestine where many other bacterial species are present. The components involved in such inter-species communication pathways will be identified and characterized. Together, these studies will provide insight into the molecular architecture of V. cholerae intra- and inter-species communication networks. Practically, results from this work could lead to the development of anti-quorum-sensing therapies for use as alternatives to traditional antibiotics.
描述(由申请人提供):人类病原体霍乱弧菌使用群体感应,其涉及称为自诱导物的化学信号分子的产生、释放和随后的检测,以响应细胞群体密度和物种复杂性的变化来调节毒力基因表达。目前已知两种霍乱弧菌自诱导物检测系统,一种用于种内通信,一种用于种间通信。本申请的长期目标是了解该细菌种内和种间群体感应信号传导的分子机制。在每个细胞外自诱导物中编码的独特信息被内部翻译成磷酸化反应调节剂LuxO的离散水平,其决定了霍乱弧菌群体感应系统的最终输出。由于磷酸异丙酯的不稳定性,磷酸化细菌反应调节剂的体内水平从未被直接测定。为了了解霍乱弧菌群体感应电路中的信号-响应输入-输出关系,我的第一个目标是开发用于定量测量霍乱弧菌细胞中磷酸-LuxO水平的方法。将两种不同的自诱导物中包含的信息整合到单个调节网络中可以使霍乱弧菌群体感应系统发挥巧合检测器的作用。或者,该回路可以通过两种自身诱导物的任何或所有组合促进不同的基因调控。我的第二个目标是通过研究每种自诱导物对特定靶基因表达的影响来区分这两种可能性。将进行所选靶基因的时间表达动力学的测量,以确定自诱导物是否一起起作用,或者是否存在响应于不同自诱导物组合的有序基因表达层级。这些研究的结果将充分定义每个调节元件在群体感应信号电路中的作用。本申请的第三个目的是鉴定存在于霍乱弧菌和其他细菌物种之间的新型化学信号通讯途径。种间交流可能使霍乱弧菌能够适应,竞争和生存在复杂的环境中,如污染的水和人类肠道,其中存在许多其他细菌物种。参与这种物种间通信途径的组件将被识别和表征。总之,这些研究将提供深入了解霍乱弧菌种内和种间通信网络的分子结构。实际上,这项工作的结果可能会导致反群体感应疗法的发展,作为传统抗生素的替代品。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Wai-Leung Ng其他文献
Wai-Leung Ng的其他文献
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{{ truncateString('Wai-Leung Ng', 18)}}的其他基金
Signaling Mechanisms in Vibrio Cholerae Parallel Quorum Sensing Pathways
霍乱弧菌平行群体感应通路中的信号机制
- 批准号:
10368054 - 财政年份:2015
- 资助金额:
$ 4.68万 - 项目类别:
SIGNALING MECHANISMS IN VIBRIO CHOLERAE PARALLEL QUORUM SENSING PATHWAYS
霍乱弧菌平行群体感应通路中的信号机制
- 批准号:
9008788 - 财政年份:2015
- 资助金额:
$ 4.68万 - 项目类别:
Signaling Mechanisms in Vibrio Cholerae Parallel Quorum Sensing Pathways
霍乱弧菌平行群体感应通路中的信号机制
- 批准号:
10579912 - 财政年份:2015
- 资助金额:
$ 4.68万 - 项目类别:
Signal Transduction in the Major Quorum-Sensing Circuit of Vibrio cholerae
霍乱弧菌主要群体感应电路中的信号转导
- 批准号:
8536203 - 财政年份:2012
- 资助金额:
$ 4.68万 - 项目类别:
Signal Transduction in the Major Quorum-Sensing Circuit of Vibrio cholerae
霍乱弧菌主要群体感应电路中的信号转导
- 批准号:
8279603 - 财政年份:2012
- 资助金额:
$ 4.68万 - 项目类别:
Intra- and inter species cell-cell communication in Vibrio cholerae
霍乱弧菌的种内和种间细胞通讯
- 批准号:
7489857 - 财政年份:2007
- 资助金额:
$ 4.68万 - 项目类别:
Intra- and inter species cell-cell communication in Vibrio cholerae
霍乱弧菌的种内和种间细胞通讯
- 批准号:
7683281 - 财政年份:2007
- 资助金额:
$ 4.68万 - 项目类别:
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