结核分枝杆菌PhoP-PhoR双组分系统研究进展

doi:10.16431/j.cnki.1671-7236.2018.11.033

摘要/Abstract

摘要：

双组分信号转导系统广泛存在于各种原核生物中，其基本结构为1个组氨酸激酶（HK）和1个反应调节剂（RR），该系统能够感知外界刺激并作出反应，使细菌能适应各种不利环境且能增强细菌在宿主体内的生存能力，对细菌的毒力和生长至关重要。文章概述了结核分枝杆菌DosS/DosT-DosR、MprA-MprB、PrrA-PrrB、PhoP-PhoR等12个双组分系统，重点介绍了PhoP-PhoR双组分系统的结构与功能。PhoP-PhoR是结核分枝杆菌最基本、最重要的双组分系统之一，由感受器PhoR和效应器PhoP组成，其中PhoR可以接受Mg^2＋、Cl^－或H^＋等外界刺激，进而驱动PhoP对靶基因的转录表达进行调控。PhoP作为一种效应蛋白，经过晶体结构解析发现，其可通过与DNA结合来实现对靶基因的调控，具体包括对细胞壁组成的控制、对脂类代谢和pH的调节、对结核分枝杆菌毒力网络的调控。此外，文章还介绍了PhoP突变株作为疫苗候选株所具有的优势，包括PhoP突变株在小鼠模型中毒力减弱，并且免疫恒河猴及豚鼠后均有一定的免疫保护性等，表明PhoP突变株具有较好的疫苗开发潜力。作者通过对PhoP-PhoR双组分系统的结构与功能，以及PhoP突变株作为疫苗候选株的研究进行综述，旨在为结核分枝杆菌的毒力机制和人类结核病疫苗的研究提供理论依据。

关键词: 结核分枝杆菌; PhoP-PhoR双组分系统; PhoP蛋白; PhoP突变体

Abstract:

The two-component signal transduction system is widely distributed in various prokaryotes.Its basic structure consist of a histidine protein kinase (HK) and a response-regulatory protein (RR).The system is essential for the virulence and growth of bacteria which can perceive various external stimuli and react,so that bacteria can adapt to various adverse conditions and enhance the survival ability in the host.In this paper,12 two-component systems of Mycobacterium tuberculosis including DosS/DosT-DosR,MprA-MprB,PrrA-PrrB and PhoP-PhoR are briefly reviewed.The structure and function of PhoP-PhoR are highlighted.PhoP-PhoR is one of the most basic and most important two component systems of Mycobacterium tuberculosis,composed of receptor PhoR and effector PhoP,in which PhoR can receive external stimuli such as Mg²⁺,Cl^- or H⁺,and then drive PhoP to regulate the transcriptional expression of target genes.As an effector protein,PhoP can be found through the analysis of crystal structure,which can be used to regulate the target gene by combining with DNA,including the control of cell wall composition,the regulation of lipid metabolism and pH,and the regulation of the virulence network of Mycobacterium tuberculosis.In addition,the advantages of PhoP mutant strain as a vaccine candidate is also introduced in the article,including the weakening of PhoP mutant strain in the mouse model,and immune protection in immunized Ganges River monkeys and guinea pigs,indicating that the PhoP mutant has a good potential for vaccine development.In this paper,the structure and function of PhoP-PhoR two-component system and the research of PhoP mutant as vaccine candidate are reviewed to provide a theoretical basis for research of the virulence mechanism of Mycobacterium tuberculosis and human tuberculosis vaccine.

Key words: Mycobacterium tuberculosis; PhoP-PhoR two-component system; PhoP protein; PhoP mutant

中图分类号:

S852.61⁺8

郭佳成, 任宁宁, 郭爱珍, 陈颖钰. 结核分枝杆菌PhoP-PhoR双组分系统研究进展[J]. 《中国畜牧兽医》, 2018, 45(11): 3253-3260.

GUO Jiacheng, REN Ningning, GUO Aizhen, CHEN Yingyu. Research Progress on Two-component System of Mycobacterium tuberculosis PhoP-PhoR[J]. , 2018, 45(11): 3253-3260.

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