Drug resistance mechanisms and novel drug targets for tuberculosis therapy

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

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.

Keywords: Drug target; Mechanism; Mycobacterium tuberculosis; Resistance; Tuberculosis.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antitubercular Agents / pharmacology*
  • Antitubercular Agents / therapeutic use
  • Drug Resistance, Bacterial* / genetics
  • Genomics
  • Humans
  • Molecular Targeted Therapy / methods*
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / physiology*
  • Tuberculosis / drug therapy*

Substances

  • Antitubercular Agents