The role of secreted effector proteins in Chlamydia trachomatis invasion
分泌效应蛋白在沙眼衣原体侵袭中的作用
基本信息
- 批准号:10268204
- 负责人:
- 金额:$ 49.01万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-22 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:ANGPTL2 geneActinsAddressAntibioticsBacteriaBacterial InfectionsBindingBlindnessCellsCervicalChlamydiaChlamydia trachomatisComplexCytoskeletal ModelingCytoskeletonDataDefectDevelopmentDisease ProgressionEMS1 geneEnsureFilopodiaGeneticGleanGoalsGuanosine Triphosphate PhosphohydrolasesHumanImpairmentIncidenceInfectionInjectionsIntegration Host FactorsInvadedKnowledgeLaboratoriesLeftMeasuresMediatingMembraneModelingMolecularNaturePathogenesisPathway interactionsPhysiologicalPrevalenceProcessProliferatingProteinsRecurrenceRoleScaffolding ProteinSexual TransmissionSignal PathwaySignal TransductionSiteType III Secretion System Pathwayknock-downmutantnovelnovel therapeutic interventionpathogenpolymerizationrecruittooluptake
项目摘要
Project Summary
Chlamydia trachomatis (C.t.) is the leading cause of non-congenital blindness and the most prevalent sexually
transmitted bacterial infection in the world, which if left untreated can result in severe consequences. All
chlamydiae are obligate intracellular bacteria and thus gaining entry into a host cell is essential for the pathogen
to complete its replicative cycle and proliferate. Despite the critical nature of the invasion process, the molecular
mechanisms and details regarding how C.t. forces its way into non-phagocytic cells remains a large knowledge
gap. A major premise of the current model suggests that invasion is facilitated by delivery of prepackaged
conventional type III secretion system (cT3SS) effector proteins into the host cell prior to pathogen entry. We
hypothesize that a subset of these cT3SS effectors coordinate active subversion of the host cytoskeleton through
direct manipulation of key regulators of actin dynamics. New data from our laboratory indicates that the cT3SS
effector protein TmeA binds to the nucleation promoting factor N-WASP, both of which we show are essential
for invasion. In Aim 1, we will mechanistically determine how TmeA regulates N-WASP and determine whether
this interaction promotes key membrane features that likely aid in bacterial entry such as; membrane ruffling,
pedestal formation, and filopodial dynamics. Given the essential nature of invasion to bacterial proliferation and
survival, C.t. likely employs multiple measures for invasion. In Aim 2, we will evaluate the complex interplay
between TarP, TepP, and TmeA and reveal the ultimate molecular effects of their effector function and describe
how the seemingly disparate pathways targeted by these effectors converge to assure chlamydial invasion.
Furthermore, we will determine whether other cT3SS effectors, only expressed in the invasive EB form of
chlamydia, are necessary for invasion of non-phagocytic cells. Detailed characterization of the bacterial and host
proteins required to promote reorganization of the actin cytoskeleton during C.t. invasion will provide a holistic
view of how intracellular pathogens, such as C.t., coordinate subversion of cytoskeletal regulators to invade host
cells.
项目摘要
沙眼衣原体(Chlamydia trachomatis(C.T.)是非先天性失明的主要原因,也是最普遍的性
在世界上传播的细菌感染,如果不加以治疗,可能会导致严重的后果。全
衣原体是专性胞内细菌,因此进入宿主细胞对病原体是必不可少的。
以完成其复制周期并进行繁殖。尽管入侵过程具有关键性质,但分子
机制和细节关于C.T.进入非吞噬细胞仍然是一个很大的知识
差距。当前模型的一个主要前提是,通过交付预包装的
传统的III型分泌系统(CT3SS)效应蛋白在病原体进入宿主细胞之前进入宿主细胞。我们
假设这些cT3SS效应器的子集通过协调宿主细胞骨架的主动颠覆
直接操纵肌动蛋白动力学的关键调节因子。我们实验室的新数据表明,cT3SS
效应蛋白TMEA与成核促进因子N-WASP结合,我们发现这两者都是必不可少的
为入侵做准备。在目标1中,我们将机械地确定TMEA如何监管N-WASP,并确定是否
这种相互作用促进了可能有助于细菌进入的关键膜特征,例如;膜褶皱,
基座的形成和丝状基座的动力学。鉴于入侵的本质是细菌繁殖和
生存,C.T.很可能采用多种手段进行入侵。在目标2中,我们将评估复杂的相互作用
TARP、TEPP和TMEA之间的关系,揭示其效应器功能的最终分子效应,并描述
这些效应器所针对的看似完全不同的途径是如何汇聚在一起,以确保衣原体入侵的。
此外,我们将确定其他cT3SS效应器是否仅以侵袭性EB形式表达
衣原体是非吞噬细胞入侵所必需的。细菌和宿主的详细特征
在CT期间促进肌动蛋白细胞骨架重组所需的蛋白质。入侵将提供一个整体的
细胞内病原体,如C.T.,如何协调颠覆细胞骨架调节因子入侵宿主
细胞。
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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{{ truncateString('Mary Weber', 18)}}的其他基金
Functional characterization of Chlamydia trachomatis inclusion membrane proteins and their role in subversion of host vesicular trafficking
沙眼衣原体包涵膜蛋白的功能特征及其在破坏宿主囊泡运输中的作用
- 批准号:
10394158 - 财政年份:2020
- 资助金额:
$ 49.01万 - 项目类别:
Functional characterization of Chlamydia trachomatis inclusion membrane proteins and their role in subversion of host vesicular trafficking
沙眼衣原体包涵膜蛋白的功能特征及其在破坏宿主囊泡运输中的作用
- 批准号:
10411625 - 财政年份:2020
- 资助金额:
$ 49.01万 - 项目类别:
Functional characterization of Chlamydia trachomatis inclusion membrane proteins and their role in subversion of host vesicular trafficking
沙眼衣原体包涵膜蛋白的功能特征及其在破坏宿主囊泡运输中的作用
- 批准号:
10596075 - 财政年份:2020
- 资助金额:
$ 49.01万 - 项目类别:
Functional characterization of Chlamydia trachomatis inclusion membrane proteins and their role in subversion of host vesicular trafficking
沙眼衣原体包涵膜蛋白的功能特征及其在破坏宿主囊泡运输中的作用
- 批准号:
10363758 - 财政年份:2020
- 资助金额:
$ 49.01万 - 项目类别:
The role of secreted effector proteins in Chlamydia trachomatis invasion
分泌效应蛋白在沙眼衣原体侵袭中的作用
- 批准号:
10468841 - 财政年份:2020
- 资助金额:
$ 49.01万 - 项目类别:
The role of secreted effector proteins in Chlamydia trachomatis invasion
分泌效应蛋白在沙眼衣原体侵袭中的作用
- 批准号:
10683148 - 财政年份:2020
- 资助金额:
$ 49.01万 - 项目类别:
The role of secreted effector proteins in Chlamydia trachomatis invasion
分泌效应蛋白在沙眼衣原体侵袭中的作用
- 批准号:
10091562 - 财政年份:2020
- 资助金额:
$ 49.01万 - 项目类别:
Nurses Helping Colorado - Regional SBIRT Training Program
护士帮助科罗拉多州 - 区域 SBIRT 培训计划
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8718224 - 财政年份:2013
- 资助金额:
$ 49.01万 - 项目类别:
Nurses Helping Colorado - Regional SBIRT Training Program
护士帮助科罗拉多州 - 区域 SBIRT 培训计划
- 批准号:
8727556 - 财政年份:2013
- 资助金额:
$ 49.01万 - 项目类别:
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