Amity Institute of Molecular Medicine and Stem Cell Research, Amity University Uttar Pradesh, Noida 201313, India.
Amity Food and Agriculture Foundation, Amity University Uttar Pradesh, Noida 201313, India.
Life Sci. 2021 Jun 1;274:119301. doi: 10.1016/j.lfs.2021.119301. Epub 2021 Mar 3.
Tuberculosis is one of the deadliest infectious diseases existing in the world since ancient times and still possesses serious threat across the globe. Each year the number of cases increases due to high drug resistance shown by Mycobacterium tuberculosis (Mtb). Available antimycobacterial drugs have been classified as First line, Second line and Third line antibiotics depending on the time of their discoveries and their effectiveness in the treatment. These antibiotics have a broad range of targets ranging from cell wall to metabolic processes and their non-judicious and uncontrolled usage in the treatment for years has created a significant problem called multi-drug resistant (MDR) tuberculosis. In this review, we have summarized the mechanism of action of all the classified antibiotics currently in use along with the resistance mechanisms acquired by Mtb. We have focused on the new drug candidates/repurposed drugs, and drug in combinations, which are in clinical trials for either treating the MDR tuberculosis more effectively or involved in reducing the time required for the chemotherapy of drug sensitive TB. This information is not discussed very adequately on a single platform. Additionally, we have discussed the recent technologies that are being used to discover novel resistance mechanisms acquired by Mtb and for exploring novel drugs. The story of intrinsic resistance mechanisms and evolution in Mtb is far from complete. Therefore, we have also discussed intrinsic resistance mechanisms of Mtb and their evolution with time, emphasizing the hope for the development of novel antimycobacterial drugs for effective therapy of tuberculosis.
结核病是自古以来世界上最致命的传染病之一，至今仍在全球范围内构成严重威胁。由于结核分枝杆菌（Mtb）表现出高度耐药性，每年的病例数量都在增加。根据发现时间和治疗效果，现有的抗分枝杆菌药物被分为一线、二线和三线抗生素。这些抗生素的作用靶点广泛，从细胞壁到代谢过程，多年来不合理和不受控制的使用在治疗中造成了一个严重的问题，称为耐多药结核病（MDR-TB）。在这篇综述中，我们总结了目前所有分类抗生素的作用机制，以及 Mtb 获得的耐药机制。我们重点介绍了新的候选药物/重新利用的药物，以及联合用药，这些药物正在临床试验中，以更有效地治疗耐多药结核病或减少治疗药物敏感结核病所需的化疗时间。这些信息在单个平台上并没有得到充分讨论。此外，我们还讨论了用于发现 Mtb 获得的新耐药机制和探索新药物的最新技术。Mtb 的固有耐药机制和进化的故事远未完成。因此，我们还讨论了 Mtb 的固有耐药机制及其随时间的进化，强调了开发新型抗分枝杆菌药物以有效治疗结核病的希望。
