Modulation of Agr system by ClpC chaperone in S. aureus
金黄色葡萄球菌中 ClpC 伴侣对 Agr 系统的调节
基本信息
- 批准号:10593669
- 负责人:
- 金额:$ 19.13万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-03-01 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:AffectAnimalsBacteriaBiochemicalBiological AssayCell DensityCell surfaceChimeric ProteinsComplexDNA BindingDataDiseaseEnabling FactorsEnvironmentFoundationsGene Expression RegulationGenesGenetic TranscriptionGenus staphylococcusGoalsGram-Positive BacteriaHomeostasisHumanImmune systemInfectionInterferometryKnowledgeLaboratoriesLifeMapsMembrane ProteinsMethodsModelingMolecular ChaperonesOperonOrganismPathogenesisPathogenicityPathway interactionsPeptide HydrolasesPeptidesPheromonePlayPolysaccharidesProcessProductionPromoter RegionsProteinsQuality ControlRNAIIIRegulationRegulatory PathwayRegulonReporterResearchRoleSmall RNASolidStaphylococcal InfectionsStaphylococcus aureusSurfaceSystemTechnologyTestingToxinVirulenceVirulence FactorsVirulentcapsuleexperimental studyextracellulargenetic approachhuman pathogenhuman tissuein vivoinsightnegative affectnoveloxidationpathogenprotein foldingquorum sensingsensorvirtualvirulence gene
项目摘要
PROJECT SUMMARY
The long-term goal of our research is to understand virulence gene regulation in Staphylococcus aureus.
S. aureus is an important human pathogen capable of causing a wide spectrum of infections in human and
animals. The pathogenicity of this organism is dependent on various virulence factors produced during infection
that are controlled by a large number of regulators. Elucidation of virulence regulation by this complex regulatory
network is central to understanding pathogenesis of this pathogen. However, despite extensive efforts, our
knowledge of virulence regulation is still very limited. We have previously identified ClpC as part of the regulatory
network capable of regulating the transcription of a large number of genes, including virulence genes. ClpC is a
protein chaperone involved in protein quality control, which does not have a DNA-binding motif. We therefore
hypothesize that ClpC interacts with transcriptional regulators to affect gene transcription. Indeed, our recent
results provided the initial evidence to support this hypothesis. One of the regulators we identified that could
interact with ClpC is AgrA, a transcriptional regulator of the AgrAC two-component system, which is part of the
Agr quorum sensing system in S. aureus. The Agr quorum sensing system also includes AgrB and AgrD that
are involved in pheromone AIP (auto-inducing peptide) production needed for Agr autoactivation at high cell
density. Agr has been shown to be a key regulator that affects the expression of many virulence genes. Our
preliminary data showed that ClpC could activate the Agr system by directly interacting with AgrA as well as by
positively affecting AIP production independent of AgrA autoactivation, suggesting that ClpC could affect Agr
regulatory system at two different pathways. Accordingly, in this application, we propose two specific aims to
study the potential mechanisms involved in this regulation. In the first aim, we will investigate how ClpC
modulates AgrA regulatory activity. In the second aim, we will study how ClpC affects AIP production. ClpC has
been shown to negatively affect regulators by partnering with ClpP protease. However, how ClpC can positively
modulate a regulatory system is virtually unknown. Our studies proposed in this application will not only probe
the potential novel mechanisms involved in gene regulation but will also advance our understanding virulence
regulation in S. aureus.
项目总结
我们研究的长期目标是了解金黄色葡萄球菌毒力基因的调控。
金黄色葡萄球菌是一种重要的人类病原体,能够在人类和
动物。这种微生物的致病力取决于感染过程中产生的各种毒力因子。
由大量监管机构控制的公司。通过这种复杂的调控阐明毒力调控
网络是了解这种病原体发病机制的核心。然而,尽管做出了广泛的努力,我们的
关于毒力调控的知识仍然非常有限。我们之前已将ClpC确定为监管部门的一部分
能够调控大量基因转录的网络,包括毒力基因。ClpC是一种
蛋白质伴侣参与蛋白质质量控制,它没有DNA结合基序。因此,我们
假设ClpC与转录调控因子相互作用影响基因转录。事实上,我们最近
结果提供了支持这一假设的初步证据。我们确定的监管机构之一可能
与ClpC相互作用的是AGRA,它是AGAC双组分系统的转录调控因子,是
金黄色葡萄球菌的AGR群体感应系统。AGR群体感应系统还包括农业B和农业D
参与了高级细胞中AGR自激活所需的信息素AIP(自动诱导肽)的产生
密度。AGR已被证明是影响许多毒力基因表达的关键调节因子。我们的
初步数据显示,ClpC可以通过与AGRA直接相互作用以及通过
正向影响AIP的产生,不依赖于AGRA的自激活,表明ClpC可能影响AGR
监管体系在两条不同的路径上。因此,在本申请中,我们提出了两个具体目标
研究这一监管涉及的潜在机制。在第一个目标中,我们将调查ClpC如何
调节AGRA的调节活动。在第二个目标中,我们将研究ClpC对AIP生产的影响。ClpC有
已被证明通过与ClpP蛋白酶合作对调节器产生负面影响。然而,ClpC如何积极地
调整一个监管体系几乎是未知的。我们在本申请中提出的研究不仅将探索
潜在的新机制涉及基因调控,但也将促进我们对毒力的理解
金黄色葡萄球菌的监管。
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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Chia Y. Lee其他文献
Sequence analysis and comparison of int and xis genes from staphylococcal bacteriophages L54a and phi 11
葡萄球菌噬菌体 L54a 和 phi 11 的 int 和 xis 基因的序列分析和比较
- DOI:
- 发表时间:
1990 - 期刊:
- 影响因子:3.2
- 作者:
Zhi‐Hai Ye;S. Buranen;Chia Y. Lee - 通讯作者:
Chia Y. Lee
Nucleotide Sequence andGenetic Characterization of Staphylococcal Bacteriophage L54aintandxisgenes
葡萄球菌噬菌体 L54aintandxis 基因的核苷酸序列和遗传特征
- DOI:
- 发表时间:
1989 - 期刊:
- 影响因子:0
- 作者:
Chia Y. Lee - 通讯作者:
Chia Y. Lee
A Rat Model of Orthopedic Implant-Associated Infection for Identification of Staphylococcal Biofilm Proteins.
用于鉴定葡萄球菌生物膜蛋白的骨科植入相关感染的大鼠模型。
- DOI:
- 发表时间:
2021 - 期刊:
- 影响因子:0
- 作者:
M. Lei;R. Gupta;Chia Y. Lee - 通讯作者:
Chia Y. Lee
Chia Y. Lee的其他文献
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{{ truncateString('Chia Y. Lee', 18)}}的其他基金
Characterization of a novel S. aureus biofilm polysaccharide
新型金黄色葡萄球菌生物膜多糖的表征
- 批准号:
10373045 - 财政年份:2021
- 资助金额:
$ 19.13万 - 项目类别:
Characterization of a novel S. aureus biofilm polysaccharide
新型金黄色葡萄球菌生物膜多糖的表征
- 批准号:
10193081 - 财政年份:2021
- 资助金额:
$ 19.13万 - 项目类别:
Virulence gene regulation in Staphylococcus aureus
金黄色葡萄球菌毒力基因调控
- 批准号:
8912102 - 财政年份:2015
- 资助金额:
$ 19.13万 - 项目类别:
Proteomic analysis of S aureus biofilm in vivo
体内金黄色葡萄球菌生物膜的蛋白质组学分析
- 批准号:
8707068 - 财政年份:2014
- 资助金额:
$ 19.13万 - 项目类别:
Proteomic analysis of S aureus biofilm in vivo
体内金黄色葡萄球菌生物膜的蛋白质组学分析
- 批准号:
8833246 - 财政年份:2014
- 资助金额:
$ 19.13万 - 项目类别:
Regulation of Staphylococcus aureus biofilm by Rbf
Rbf 对金黄色葡萄球菌生物膜的调节
- 批准号:
8078999 - 财政年份:2007
- 资助金额:
$ 19.13万 - 项目类别:
Regulation of Staphylococcus aureus biofilm by Rbf
Rbf 对金黄色葡萄球菌生物膜的调节
- 批准号:
7640712 - 财政年份:2007
- 资助金额:
$ 19.13万 - 项目类别:
Regulation of Staphylococcus aureus biofilm by Rbf
Rbf 对金黄色葡萄球菌生物膜的调节
- 批准号:
7900598 - 财政年份:2007
- 资助金额:
$ 19.13万 - 项目类别:
Regulation of Staphylococcus aureus biofilm by Rbf
Rbf 对金黄色葡萄球菌生物膜的调节
- 批准号:
7320366 - 财政年份:2007
- 资助金额:
$ 19.13万 - 项目类别:
Regulation of Staphylococcus aureus biofilm by Rbf
Rbf 对金黄色葡萄球菌生物膜的调节
- 批准号:
7459011 - 财政年份:2007
- 资助金额:
$ 19.13万 - 项目类别:
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