Regulation and composition of ER-inclusion contacts at key stages of the Chlamydia developmental cycle
Regulation and composition of ER-inclusion contacts at key stages of the Chlamydia developmental cycle
批准号:
10528480
负责人:
ISABELLE DERRE
金额:
$23.26万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-12-01 至 2024-11-30
关键词:
AntibioticsBacteriaBacterial InfectionsBindingBiologicalBiotinC-terminalCellsCellular biologyChlamydiaChlamydia InfectionsChlamydia trachomatisCholesterolCicatrixCommunicationComplexCytolysisDataDevelopmentEctopic PregnancyEndoplasmic ReticulumEnsureEnvironmentEpitheliumFemaleFunctional disorderGrowthImmunityInfectionInfertilityIntegration Host FactorsLabelLeftLipidsMediatingMembraneMembrane BiologyMembrane ProteinsMicrobiologyMolecularOrganellesPelvic Inflammatory DiseasePhasePhosphorylationPhosphotransferasesProcessProteinsProteomeRegulationReproductive HealthRoleSerineSexually Transmitted DiseasesSiteStructureTestingTimeTissuesVaccinesWomanWorkcandidate identificationdesignfollow-upgenital infectionhuman diseaseinfection ratenovelpathogenpathogenic bacteriapreventrecruitreproductive organtherapeutically effectivetrafficking
中文摘要
总结
沙眼衣原体是全世界细菌性传播感染的主要原因。
没有疫苗。感染通常是无症状的,未经治疗,导致组织瘢痕形成,
对女性生殖健康的长期影响。C.沙眼是一种专性细胞内细菌途径,
在膜结合隔室内经历双相发育周期的原,称为inclu,
锡永。为了在这种封闭的环境中茁壮成长,C。沙眼必须与胞质宿主因子和有机体相互作用,
nelles,一个由衣原体特异性包涵体膜蛋白(Inc蛋白)插入介导的过程
进入包合膜。一种这样的相互作用是包含体的离散部分之间的紧密接触,
锡永网(ER)是内质网的重要组成部分。这些结构被称为ER-包含膜
联系网站(MCS)。我们对ER-包涵体MCS的初步表征表明富含Inc蛋白,
具有功能、约束和监管能力的宿主因素。其中一些成分的消耗是
对细菌生长有害,强调了ER-包涵体MCS在建立
复制生态位在整个发育周期中观察到ER-包涵体MCS;然而,
不清楚功能性、结构性和规则性成分是否以及如何在颞叶组装中合作,
接触的溶解性和特定成分的富集。在这里,我们将探讨如何ER包容
MCS组装受到管制(目标1),如果特定组件的关联因组装阶段而异,
发展周期(目标2)。总之,拟议的研究将阐明ER-包涵体的组成部分
MCS允许建立C.沙眼复制生态位,这将指导设计有效的
治疗学
英文摘要
SUMMARY
Chlamydia trachomatis is the leading cause of sexually transmitted infections of bacterial origin worldwide.
Vaccines are not available. Infections are often asymptomatic and left untreated, resulting in tissue scarring and
long-term consequences on female reproductive health. C. trachomatis is an obligate intracellular bacterial path-
ogen that undergoes a bi-phasic development cycle within a membrane bound compartment termed the inclu-
sion. To thrive in this confined environment, C. trachomatis must interact with cytosolic host factors and orga-
nelles, a process mediated by the insertion of Chlamydia specific Inclusion membrane proteins (Inc proteins)
into the inclusion membrane. One such interaction is the intimate contact between discrete sections of the inclu-
sion membrane and the endoplasmic reticulum (ER). These structures are referred to as ER-Inclusion membrane
contact sites (MCS). Our initial characterization of ER-Inclusion MCS indicates an enrichment in Inc proteins and
host factors with functional, tethering and regulatory capacities. Depletion of some of these components is
detrimental to bacterial growth, underscoring the important role of ER-Inclusion MCS in establishing the
replicative niche. ER-Inclusion MCS are observed throughout the developmental cycle; however, it remains
unclear if and how functional, structural and regularoty components cooperate in the temporal assembly and
dissambly of the contact, and enrichment of specific components. Here we will investigate how ER-Inclusion
MCS assembly is regulated (Aim 1) and if association of specific components varies depending on the stage of
the developmental cycle (Aim 2). Altogether, the proposed studies will elucidate how components of ER-Inclusion
MCS allows for the establishment of the C. trachomatis replicative niche, which will guide the design of effective
therapeutics.
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
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