Issues with the current drugs for Mycobacterium tuberculosis cure and potential of cell envelope proteins for new drug discovery

Indian J Tuberc. 2023 Jul;70(3):286-296. doi: 10.1016/j.ijtb.2023.03.015. Epub 2023 Apr 1.

Abstract

Mycobacterium tuberculosis has been the smartest pathogen ever and a challenge to drug development. Its replicative machinery is unique, so targeting the same for killing the pathogen remains a challenge. Our body typically throws out the drugs before they see the bacterium multiply. The pathogen has also learned how to remove drugs from its internal chambers and not allow them to reach their targets. Another strategy for Mtb is the mutation of the targets to reject drug binding and bypass the drug's inhibitory actions. In this review, we tried to explore possible targets on the outer side of the bacterial cell. We have also explored if those targets are promising enough and if there are drugs or inhibitors available. We also discuss the essential proteins and why they remain to be a good target. We concluded that the cell envelope has got a few proteins that can be targeted in isolation or maybe along with other machinery while making the outer environment more conducive for penetration of current drugs or newly proposed drugs.

Keywords: Cell envelope; Inhibitor; Mycobacterium tuberculosis; New drugs; Target site.

Publication types

  • Review

MeSH terms

  • Antitubercular Agents / pharmacology
  • Antitubercular Agents / therapeutic use
  • Bacterial Proteins / genetics
  • Drug Discovery
  • Humans
  • Mycobacterium tuberculosis* / genetics

Substances

  • Antitubercular Agents
  • Bacterial Proteins