Chaperone Mining of the Chlamydia Type Three Secretion System
衣原体三型分泌系统的伴侣挖掘
基本信息
- 批准号:7440251
- 负责人:
- 金额:$ 35.66万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-07-01 至 2011-06-30
- 项目状态:已结题
- 来源:
- 关键词:AppearanceAttenuatedBacteriaBacterial TypingBindingBiological AssayCellsCharacteristicsChlamydiaChlamydia InfectionsChlamydia trachomatisChromosome MappingChromosomesClassCloningComplexCytosolDNA-Directed RNA PolymeraseDevelopmentElectronsElementsEventGene ExpressionGene StructureGenesGeneticGenetic TranscriptionGenomicsGoalsGram-Negative BacteriaGrowthHarvestImmunoelectron MicroscopyImmunologicsInfection preventionInvadedLeadLibrariesLightLocationMapsMethodsMicroscopicMiningMolecular ChaperonesNaturePathogenicity IslandPlasmidsPlayPreventionPrincipal InvestigatorPropertyProtein SecretionProteinsPublic HealthRecombinant ProteinsRegulationRegulatory ElementRelative (related person)ReportingResearch PersonnelReverse Transcriptase Polymerase Chain ReactionRoleSexually Transmitted DiseasesSignal TransductionStagingStructural GenesSystemTestingTimeTranscriptional RegulationVirulenceWorkYersiniabasedesigngenetic regulatory proteinpathogenpreventprogramspromoterprotein functiontooltranscription factoryeast two hybrid system
项目摘要
DESCRIPTION (provided by applicant): Chlamydia trachomatis is a leading cause of sexually transmitted diseases. Understanding how this pathogen invades and replicates in host cells is fundamental to our efforts to design effective therapies that can aid in the prevention of Chlamydia infections. It has recently been shown that Chlamydia possesses genes for a type three secretion (TTS) system. In other bacteria TTS systems are a powerful virulence component shared by pathogens that allow them to subvert and invade the host. TTS systems are composed of several proteins that interact in a highly regulated manner. Chlamydia does not have a classic genetic system with which to study this complex system, thereby making this a challenging task. However, a common element to all TTS systems are the TTS chaperones which serve as a lynchpin interacting with other TTS key elements, namely, structural, effectors and regulatory proteins. We plan to exploit TTS chaperones in order to identify and characterize other key chlamydial TTS proteins. Once identified the role these proteins play, i.e. effectors, translocon or transcriptional regulator, will be established. Specifically in Aim 1 we will use TTS chaperones as bait in pull down assays and in a bacterial two-hybrid system, using targeted and genomic-wide cloning. To further characterize the proteins identified, in Aim 2 we will establish the temporal relationship of the proteins to the Chlamydia developmental cycle. Proteins will be characterized as to time of appearance and location throughout the developmental cycle, using RT-PCR, light and immuno-electron microscopy. We will also establish if proteins identified have a characteristic property of a TTS effector molecule by determining if they can be secreted by a heterologous TTS system. In other pathogens, proteins interacting with TTS chaperones have been shown to play a role in transcriptional regulation of TTS. However, nothing is known of the regulation of the Chlamydia TTS so we will first have to establish the transcriptional organization in order to determine whether the proteins identified have a role in the transcriptional regulation of the Chlamydia TTS. This will be accomplished in Aim 3 by: mapping promoters and determining the form of RNA polymerase responsible for transcription; identifying transcriptional regulators by binding to predicted regulatory elements; finally, testing the proteins identified in Aim 1 for their potential to function as a transcriptional regulator. Accomplishing these goals will aid in finding and putting the pieces of the TTS puzzle together to determine how this system functions in Chlamydia. Preventing and controlling Chlamydia infections is of great public health concern. Having an understanding of the critical elements of the Chlamydia TTS system should lead to the development of strategies to subvert the TTS system with the ultimate goal of attenuating or preventing infections with this pathogen.
描述(申请人提供):沙眼衣原体是性传播疾病的主要原因。了解这种病原体如何在宿主细胞中入侵和复制,对于我们努力设计有效的治疗方法,有助于预防衣原体感染是至关重要的。最近发现衣原体具有三型分泌系统(TTS)的基因。在其他细菌中,TTS系统是病原体共享的强大毒力成分,使它们能够颠覆和入侵宿主。TTS系统由几种以高度调控方式相互作用的蛋白质组成。衣原体没有一个经典的遗传系统来研究这个复杂的系统,因此这是一个具有挑战性的任务。然而,所有TTS系统的一个共同元件是TTS伴侣,它是与其他TTS关键元件相互作用的关键,即结构、效应和调节蛋白。我们计划开发TTS伴侣蛋白,以鉴定和鉴定其他关键的衣原体TTS蛋白。一旦确定了这些蛋白质所起的作用,即效应器、转位或转录调节因子,就会被确定。具体地说,在目标1中,我们将使用TTS伴侣作为下拉试验中的诱饵,并在细菌双杂交系统中使用定向和全基因组克隆。为了进一步确定所鉴定的蛋白质的特征,在目标2中,我们将建立蛋白质与衣原体发育周期的时间关系。利用RT-PCR、光镜和免疫电子显微镜对蛋白质在整个发育周期中出现的时间和位置进行表征。我们还将确定所鉴定的蛋白质是否具有TTS效应分子的特征属性,方法是确定它们是否可以由异源TTS系统分泌。在其他病原体中,与TTS伴侣相互作用的蛋白质已被证明在TTS的转录调控中发挥作用。然而,对衣原体TTS的调控尚不清楚,因此我们首先必须建立转录组织,以确定所鉴定的蛋白质是否在衣原体TTS的转录调控中发挥作用。在目标3中,这将通过以下方式完成:绘制启动子图并确定负责转录的RNA聚合酶的形式;通过与预测的调控元件结合来确定转录调节因子;最后,测试在目标1中确定的蛋白质作为转录调节因子的潜力。实现这些目标将有助于找到TTS拼图的碎片,并将其组合在一起,以确定该系统在衣原体中如何发挥作用。预防和控制衣原体感染是一个重大的公共卫生问题。对衣原体TTS系统的关键要素的了解应导致制定颠覆TTS系统的战略,最终目标是减轻或预防这种病原体的感染。
项目成果
期刊论文数量(0)
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ELLENA Marie PETERSON其他文献
ELLENA Marie PETERSON的其他文献
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{{ truncateString('ELLENA Marie PETERSON', 18)}}的其他基金
Chaperone Mining of the Chlamydia Type Three Secretion System
衣原体三型分泌系统的伴侣挖掘
- 批准号:
7137362 - 财政年份:2006
- 资助金额:
$ 35.66万 - 项目类别:
Chaperone Mining of the Chlamydia Type Three Secretion System
衣原体三型分泌系统的伴侣挖掘
- 批准号:
7242501 - 财政年份:2006
- 资助金额:
$ 35.66万 - 项目类别:
Chaperone Mining of the Chlamydia Type Three Secretion System
衣原体三型分泌系统的伴侣挖掘
- 批准号:
7630473 - 财政年份:2006
- 资助金额:
$ 35.66万 - 项目类别:
Chaperone Mining of the Chlamydia Type Three Secretion System
衣原体三型分泌系统的伴侣挖掘
- 批准号:
7878514 - 财政年份:2006
- 资助金额:
$ 35.66万 - 项目类别:
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