Drug resistance in Mycobacterium tuberculosis and targeting the l,d-transpeptidase enzyme

Drug Dev Res. 2019 Feb;80(1):11-18. doi: 10.1002/ddr.21455. Epub 2018 Oct 12.

Abstract

Tuberculosis (TB) is a disease that has afflicted mankind for thousands of years, but in the last seven decades, much progress has been made in anti-TB therapy. Early drugs, such as para-aminosalicylic acid, streptomycin, isoniazid, and rifamycins were very effective in combatting the disease, giving rise to the hope that TB would be eradicated from the face of the earth by 2010. Despite that optimism, TB continues to kill more than a million people annually worldwide. A major reason for our inability to contain TB is the emergence drug resistance in Mycobacterium tuberculosis. This commentary is based on our recent publication on the structure of l,d-transpeptidase enzyme, relevant to drug resistance. As a background, we briefly outline the history and development of anti-TB therapy. Based on the crystal structure, we suggest a potential direction for designing more potent drugs against TB.

Keywords: drug resistance; mycobacterium tuberculosis; transpeptidase.

Publication types

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

MeSH terms

  • Animals
  • Antitubercular Agents / administration & dosage*
  • Cell Wall / drug effects
  • Cell Wall / metabolism
  • Drug Delivery Systems / methods*
  • Drug Delivery Systems / trends
  • Drug Resistance, Bacterial / drug effects*
  • Drug Resistance, Bacterial / physiology
  • Humans
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / enzymology
  • Peptidyl Transferases / antagonists & inhibitors*
  • Peptidyl Transferases / metabolism
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Tuberculosis / drug therapy*
  • Tuberculosis / enzymology

Substances

  • Antitubercular Agents
  • Peptidyl Transferases