The Mycobacterium tuberculosis Cell Wall: An Alluring Drug Target for Developing Newer Anti-TB Drugs-A Perspective

Chem Biol Drug Des. 2024 Sep;104(3):e14612. doi: 10.1111/cbdd.14612.

Abstract

The Mycobacterium cell wall is a capsule-like structure comprising of various layers of biomolecules such as mycolic acid, peptidoglycans, and arabinogalactans, which provide the Mycobacteria a sort of cellular shield. Drugs like isoniazid, ethambutol, cycloserine, delamanid, and pretomanid inhibit cell wall synthesis by inhibiting one or the other enzymes involved in cell wall synthesis. Many enzymes present across these layers serve as potential targets for the design and development of newer anti-TB drugs. Some of these targets are currently being exploited as the most druggable targets like DprE1, InhA, and MmpL3. Many of the anti-TB agents present in clinical trials inhibit cell wall synthesis. The present article covers a systematic perspective of developing cell wall inhibitors targeting various enzymes involved in cell wall biosynthesis as potential drug candidates for treating Mtb infection.

Keywords: DprE1; InhA; MmpL3; anti‐TB agents; drug resistance; mycobacteria; non‐tuberculous mycobacteria; tuberculosis.

Publication types

  • Review

MeSH terms

  • Alcohol Oxidoreductases
  • Antitubercular Agents* / chemistry
  • Antitubercular Agents* / pharmacology
  • Bacterial Proteins* / antagonists & inhibitors
  • Bacterial Proteins* / metabolism
  • Cell Wall* / drug effects
  • Cell Wall* / metabolism
  • Humans
  • Membrane Transport Proteins
  • Mycobacterium tuberculosis* / drug effects
  • Mycobacterium tuberculosis* / metabolism
  • Mycolic Acids / metabolism
  • Oxidoreductases / antagonists & inhibitors
  • Oxidoreductases / metabolism
  • Tuberculosis / drug therapy

Substances

  • Antitubercular Agents
  • Bacterial Proteins
  • Oxidoreductases
  • InhA protein, Mycobacterium
  • MmpL3 protein, Mycobacterium tuberculosis
  • DprE1 protein, Mycobacterium tuberculosis
  • Mycolic Acids
  • Alcohol Oxidoreductases
  • Membrane Transport Proteins