结核分枝杆菌毒力因子蛋白酪氨酸磷酸酶PtpA转录调控和分泌机理

Transcriptional and secretion of Mycobacterium tuberculosis virulence factor protein tyrosine phosphatase A (PtpA)

摘要:

结核分枝杆菌感染引起的结核病疫情依然严峻。感染的结核菌可分泌一系列效应分子调控、干扰和逃逸宿主免疫。本文综述蛋白酪氨酸磷酸酶PtpA在结核菌感染中发挥的重要作用：经多条途径抑制宿主天然免疫、细胞凋亡及吞噬体-溶酶体融合、调控宿主能量代谢等逃逸免疫杀伤。作为候选药物靶标，靶向PtpA的抑制剂设计、筛选及药物研发较为迟缓，因为PtpA与宿主蛋白酪氨酸磷酸酶hLMW-PTP具有较高一致性。为了进一步探索靶向该分子的更佳途径，分析了ptpA基因转录及PtpA蛋白分泌方面的研究进展及存在问题，为靶向PtpA的其他途径提供参考。

关键词:结核分枝杆菌，蛋白酪氨酸磷酸酶，PtpA，转录调控，分泌机制

Abstract:

The global epidemic of tuberculosis caused by Mycobacterium tuberculosis (Mtb) is still grim. During host infection, Mtb secretes a series of effector molecules into human macrophage to regulate, modulate host immunization pathway and finally escape from the immune killing. Here, we summarized the critical roles of protein tyrosine phosphatase A (PtpA) during Mtb infection, such as inhibit the innate immunity, apoptosis, phagosome-lysosome fusion by interfering multiple pathways and modulate macrophage bioenergetics state. PtpA has been assumed as an important drug target for a long time. However, it is beset with the high similarity with human protein tyrosine phosphatase hLMW-PTP in inhibitor design and screening. At last, the research status and problems need to be revealed in Mtb PtpA transcriptional regulation and secretion pathway was analyzed and discussed, which will provide us a new way to block PtpA’s function.

Key words:Mycobacterium tuberculosis, protein tyrosine phosphatase, PtpA, transcriptional regulation, secretion mechanism