Mechanisms of Developmental Regulation in Chlamydia

项目摘要/摘要 衣原体是危害人类健康的重要病原体之一。 透视。向世界卫生组织报告了150多万例衣原体感染病例 美国疾病控制与预防中心每年都会发生这种疾病，使其成为美国最常见的传染病。 衣原体引起一种不寻常的细胞内感染，在这种感染中有 在细菌的两种发育形式之间：基本体(EB)，它是 有传染性但处于休眠状态的网状小体(RB)，它是细胞内的， 复制形态。基因表达仅限于RBS，而转录沉默在EBS中 被归因于两个组蛋白样蛋白HctA和HctB的DNA缩合。 我们假设了第二种沉默机制，即EBS中的RNA聚合酶是 以可逆的方式抑制，受3型分泌(T3S)活性控制。在……里面 目的1我们将研究T3S伴侣Scc4如何与另外两个T3S蛋白一起， 协调调节RNA聚合酶活性和T3S分泌活性。在目标2中，我们 将调查第二个T3S伴侣Scc2，我们建议将其作为T3S调节的 衣原体转录的消音器。在目标3中，我们将研究组蛋白样蛋白以 确定它们是统一沉默转录，还是以特定于启动子的方式沉默。这些 研究将确定EBS转录沉默的机制，EBS是一个重要的 衣原体胞内感染发育基因调控的特点及意义 潜在的治疗靶点。

Project Summary/Abstract Chlamydia is one of the most important infectious agents from a public health perspective. More than 1.5 million cases of chlamydial infections are reported to the CDC annually, making it the most commonly reported infectious disease in the U.S. Chlamydia causes an unusual intracellular infection in which there is conversion between two developmental forms of the bacterium: the elementary body (EB), which is the infectious but dormant form, and the reticulate body (RB), which is the intracellular, replicating form. Gene expression is limited to RBs, and transcriptional silencing in EBs has been attributed to DNA condensation by two histone-like proteins, HctA and HctB. We hypothesize a second silencing mechanism in which RNA polymerase in EBs is inhibited in a reversible manner that is controlled by Type 3 secretion (T3S) activity. In Aim 1 we will study how a T3S chaperone Scc4, together with two other T3S proteins, coordinately regulates RNA polymerase activity and T3S secretion activity. In Aim 2, we will investigate a second T3S chaperone Scc2 that we propose as a T3S-regulated silencer of chlamydial transcription. In Aim 3, we will study the histone-like proteins to determine if they silence transcription uniformly or in a promoter-specific manner. These studies will define the mechanisms of transcriptional silencing in EBs, which is a central feature of developmental gene regulation in the intracellular Chlamydia infection and a potential therapeutic target.