Mycobacterial Metabolism and Antibiotic Research Laboratory, The Francis Crick Institute, London NW1 1AT, United Kingdom; GSK-Francis Crick Institute Linklabs, Medicinal Science and Technology, GlaxoSmithKline, Stevenage SG1 2NY, United Kingdom.
Mycobacterial Metabolism and Antibiotic Research Laboratory, The Francis Crick Institute, London NW1 1AT, United Kingdom.
Curr Opin Microbiol. 2022 Oct;69:102191. doi: 10.1016/j.mib.2022.102191. Epub 2022 Aug 12.
Tuberculosis (TB) persists as a major global health issue and a leading cause of death by a single infectious agent. The global burden of TB is further exacerbated by the continuing emergence and dissemination of strains of Mycobacterium tuberculosis resistant to multiple antibiotics. The need for novel drugs that can be used to shorten the course for current TB drug regimens as well as combat the persistent threat of antibiotic resistance has never been greater. There have been significant advances in the discovery of de novo TB treatments, with the first TB-specific drugs in 45 years approved for use. However, there are still issues that restrict the pipeline of new antitubercular chemotherapies. The rate of failure of TB drug candidates in clinical trials remains high, while the validation of new TB drug targets and subsequent identification of novel inhibitors remains modest.
结核病（TB）仍然是一个重大的全球健康问题，也是单一传染病原体导致死亡的主要原因。由于耐多种抗生素结核分枝杆菌菌株的不断出现和传播，结核病的全球负担进一步加重。人们迫切需要新型药物，可以缩短当前结核病药物治疗方案的疗程，同时应对抗生素耐药性的持续威胁。在发现新的结核病治疗方法方面取得了重大进展，45 年来首次批准了专门用于结核病的药物。然而，仍然存在一些限制新抗结核化学疗法管道的问题。结核病候选药物在临床试验中的失败率仍然很高，而新的结核病药物靶点的验证和随后新型抑制剂的鉴定仍然较为有限。
