结核病治疗的耐药机制和新的药物靶点。

Drug resistance mechanisms and novel drug targets for tuberculosis therapy.

机构信息

State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China.

State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Institute of Chemical Biology and Drug Discovery, Stony Brook University-State University of New York, Stony Brook, NY 11794-3400, USA.

出版信息

J Genet Genomics. 2017 Jan 20;44(1):21-37. doi: 10.1016/j.jgg.2016.10.002. Epub 2016 Oct 11.

DOI:10.1016/j.jgg.2016.10.002

PMID:28117224

Abstract

Drug-resistant tuberculosis (TB) poses a significant challenge to the successful treatment and control of TB worldwide. Resistance to anti-TB drugs has existed since the beginning of the chemotherapy era. New insights into the resistant mechanisms of anti-TB drugs have been provided. Better understanding of drug resistance mechanisms helps in the development of new tools for the rapid diagnosis of drug-resistant TB. There is also a pressing need in the development of new drugs with novel targets to improve the current treatment of TB and to prevent the emergence of drug resistance in Mycobacterium tuberculosis. This review summarizes the anti-TB drug resistance mechanisms, furnishes some possible novel drug targets in the development of new agents for TB therapy and discusses the usefulness using known targets to develop new anti-TB drugs. Whole genome sequencing is currently an advanced technology to uncover drug resistance mechanisms in M. tuberculosis. However, further research is required to unravel the significance of some newly discovered gene mutations in their contribution to drug resistance.

摘要

耐药结核病（TB）对全球范围内成功治疗和控制结核病构成了重大挑战。自化学疗法时代开始，就已经存在对抗结核药物的耐药性。人们对抗结核药物耐药机制有了新的认识。更好地了解耐药机制有助于开发快速诊断耐药结核病的新工具。迫切需要开发具有新靶点的新药，以改善目前的结核病治疗方法，并防止结核分枝杆菌出现耐药性。本综述总结了抗结核药物耐药机制，为开发新的结核治疗药物提供了一些可能的新靶点，并讨论了利用已知靶点开发新的抗结核药物的有用性。全基因组测序是目前揭示结核分枝杆菌耐药机制的一项先进技术。然而，还需要进一步研究来揭示一些新发现的基因突变在耐药性中的意义。