结核杆菌PhoPR双组分系统对新疆地区广泛流行的耐药结核杆菌临床分离株耐药性产生的调控作用及其机制研究

The recent researches have found that the phoPR two-component system of Mycobacterium tuberculosis is the most basic and important control system which could induce changes in the external environment, and make the corresponding reaction. The system plays a key role in identifying environmental signal molecules and inducing environment changes, simultaneously it plays an important role in regulating growth, differentiation, metabolism, propagation, osmotic regulation, toxicity, chemotaxis , variability and pathogenicity of Mycobacterium tuberculosis in host body. Based on the above theoretical considerations, this research takes the wide prevalence of drug-resistant clinical Mycobacterium tuberculosis isolate strains in Xinjiang region, and established Mycobacterium tuberculosis PhoPR two-component system over expression of drug resistant Mycobacterium tuberculosis isolate strains, and established Mycobacterium tuberculosis PhoPR two-component system deletion mutation of drug-resistant Mycobacterium tuberculosis strains as Research Objects. The research is to analysis and study the regulation and mechanism that Mycobacterium tuberculosis PhoPR two-component system reacts at the drug-resistant Mycobacterium tuberculosis strains with wide prevalence in Xinjiang region, then to reveal the mechanism that Mycobacterium tuberculosis PhoPR two-component system reacts at the drug-resistant Mycobacterium tuberculosis strains in Xinjiang region, and provide theoretical basis in clarifying the mechanisms of drug resistance in Mycobacterium tuberculosis, which has an important scientific value and social significance for effective prophylaxis and treatment of tuberculosis.

近年研究发现，结核杆菌PhoPR双组分系统是结核杆菌最基本、最重要的感应外界环境变化，并做出相应反应的调控系统；该系统在结核杆菌识别外界环境的信号分子和感受环境变化中起重要作用，同时对结核杆菌在宿主体内的生长、分化、代谢、繁殖、渗透调节、毒性、趋化性、变异性和致病性等方面发挥着重要的调控作用。基于这些理论依据考虑，该项目研究以新疆地区广泛流行的耐药结核杆菌临床分离株、构建的结核杆菌PhoPR双组分系统过表达的各耐药结核杆菌菌株、和构建的结核杆菌PhoPR双组分系统缺失突变的各耐药结核杆菌菌株等为研究对象，全面系统的比较分析和探讨研究结核杆菌PhoPR双组分系统对新疆地区广泛流行的耐药结核杆菌耐药性产生的调控作用及其机制，以期研究揭示结核杆菌PhoPR双组分系统对耐药结核杆菌耐药性产生的调控作用机制，为阐明结核杆菌的耐药机制提供理论依据，对结核病的有效防治具有重要的科学价值和社会意义。

结核杆菌PhoPR双组分系统是结核杆菌最基本、最重要的感应外界环境变化，并做出相应反应的调控系统；该系统在结核杆菌识别外界环境的信号分子和感受环境变化中起重要作用，同时对结核杆菌在宿主体内的生长、分化、代谢、繁殖、渗透调节、毒性、趋化性、变异性和致病性等方面发挥着重要的调控作用。基于这些理论依据考虑，该项目研究以新疆地区广泛流行的耐药结核杆菌临床分离株、构建的结核杆菌PhoPR双组分系统过表达的各耐药结核杆菌菌株、和构建的结核杆菌PhoPR双组分系统缺失突变的各耐药结核杆菌菌株等为研究对象，全面系统的比较分析和探讨研究了结核杆菌PhoPR双组分系统对新疆地区广泛流行的耐药结核杆菌耐药性产生的调控作用及其机制，研究揭示了结核杆菌PhoPR双组分系统对耐药结核杆菌耐药性产生的调控作用机制，为阐明结核杆菌的耐药机制提供了理论依据，对结核病的有效防治具有重要的科学价值和社会意义。