Medical College of Nanchang University, 461 Bayi Road, Nanchang, Jiangxi 330066, China.
Curr Drug Targets. 2013 Jun 1;14(6):676-99. doi: 10.2174/1389450111314060009.
Tuberculosis (TB) is an infectious disease caused by the pathogen Mycobacterium tuberculosis (M. tuberculosis), killing about two million people worldwide each year. An increase in the prevalence of drug-resistant strains of M. tuberculosis in the past decades has renewed focus on the development of new drugs that can treat both drug-sensitive and resistant TB infections. M. tuberculosis evades the host immune system and drug regimes by entering dormant phase within macrophage. As a consequence, there is a pressing need for new vaccines and antimicrobials to treat persistent infections. As clinically used antibiotics target very few essential functions of mycobacterium, it is rational that identification of new targets that are essential for bacterial growth and survival can serve as starting point for designing of novel drugs to cure both drug-sensitive and resistant TB infections. With the development of molecular biology and structural biology and the availability of the genome sequence of M. tuberculosis, some success has been achieved in the identification of new targets in M. tuberculosis and their relevant inhibitors. This review summarizes about ninety important targets that participate in a range of diverse physiological processes in M. tuberculosis and seven new drugs currently in clinical phase 2 or 3 trials. In addition, promising inhibitors with novel mechanisms of action and clinical vaccine candidates are highlighted.
结核病（TB）是一种由病原体结核分枝杆菌（M. tuberculosis）引起的传染病，每年在全球导致约 200 万人死亡。在过去几十年中，M. tuberculosis 耐药菌株的流行率增加，这再次引起了人们对开发新药物的关注，这些药物可以治疗敏感和耐药性的 TB 感染。M. tuberculosis 通过进入巨噬细胞的休眠期来逃避宿主免疫系统和药物治疗。因此，迫切需要新的疫苗和抗菌药物来治疗持续感染。由于临床使用的抗生素针对的是分枝杆菌非常有限的几个必需功能，因此，鉴定对细菌生长和存活至关重要的新靶点，可以作为设计治疗敏感和耐药性 TB 感染的新型药物的起点。随着分子生物学和结构生物学的发展以及 M. tuberculosis 基因组序列的获得，在鉴定 M. tuberculosis 中的新靶点及其相关抑制剂方面已经取得了一些成功。本文综述了约 90 个参与 M. tuberculosis 多种生理过程的重要靶点，以及目前处于临床 2 期或 3 期试验的 7 种新药。此外，还强调了具有新型作用机制的有前途的抑制剂和临床疫苗候选物。
