应对宿主产生的各种压力环境是结核分枝杆菌（Mtb）成功感染的关键环节，对负责转录的RNA聚合酶（RNAP）活性的调控在压力应答过程中发挥重要作用。目前已经发现多个Mtb RNAP的激活蛋白，但结合到Mtb RNAP抑制其活性的蛋白还未见报道。我们前期研究发现功能未知的Rv1830蛋白可以与Mtb RNAP相互作用，并抑制其转录活性。本项目拟在此基础上，采用分子、生化、遗传学等技术手段，鉴定Rv1830与RNAP的互作位点，确定Rv1830抑制RNAP活性的作用方式，探究该调控作用在分枝杆菌低pH、低氧、寡营养、活性氧、活性氮等压力应答和感染过程中的功能，系统阐释Rv1830抑制RNAP活性的分子机制及生理意义。本项目将通过揭示Rv1830蛋白的生理功能，回答RNAP活性抑制如何在分枝杆菌感染过程中发挥作用这一基础科学问题，将为针对转录及调控过程开发新的药物作用靶点提供理论依据。

The successful infection of Mycobacterium tuberculosis (Mtb) relies on its ability to sense and respond to environmental stresses produced by host cells. For bacteria, stress responses are primarily mediated through the regulation of gene expression. RNA polymerase is the only enzyme in charge of transcription in bacteria and is a key target for transcriptional regulation. Activators, which bind to Mtb RNAP to promote its activity, have been recently identified. However, repressor that interacts with Mtb RNAP to inhibit its activity remains to be characterized. In our previous work, we have found that an uncharacterized protein in Mtb, Rv1830, directly binds to Mtb RNAP and represses its activity. Based on these observations, we intend to investigate the mechanism for the regulation of Rv1830 to Mtb RNAP and reveal the physiological roles of this regulatory process. For this purpose, we will apply molecular, biochemical and genetic approaches to identify the amino acid residues essential for interaction between Rv1830 and Mtb RNAP proteins, to determine the transcription step(s) regulated by Rv1830 protein, and to explore the roles of this regulatory process in response to low pH, hypoxia, nutrition starvation, reactive oxygen and nitrogen stresses and in mycobacterial infection. This project will, for the first time, reveal the function of Rv1830 protein and clarify a mechanism for the repression to Mtb RNAP activity during infection, which will provide important information for developing new drug target(s) to control mycobacterial infection.