Targeting isocitrate lyase for the treatment of latent tuberculosis

Drug Discov Today. 2017 Jul;22(7):1008-1016. doi: 10.1016/j.drudis.2017.04.012. Epub 2017 Apr 27.

Abstract

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that can remain dormant for many years before becoming active. One way to control and eliminate TB is the identification and treatment of latent TB, preventing infected individuals from developing active TB and thus eliminating the subsequent spread of the disease. Isocitrate lyase (ICL) is involved in the mycobacterial glyoxylate and methylisocitrate cycles. ICL is important for the growth and survival of M. tuberculosis during latent infection. ICL is not present in humans and is therefore a potential therapeutic target for the development of anti-TB agents. Here, we explore the evidence linking ICL to persistent survival of M. tuberculosis. The structure, mechanism and inhibition of the enzyme is also discussed.

Publication types

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

MeSH terms

  • Animals
  • Antitubercular Agents / pharmacology
  • Antitubercular Agents / therapeutic use
  • Citrates / metabolism
  • Drug Resistance, Bacterial
  • Glyoxylates / metabolism
  • Humans
  • Isocitrate Lyase / antagonists & inhibitors*
  • Isocitrate Lyase / chemistry
  • Isocitrate Lyase / metabolism
  • Latent Tuberculosis / drug therapy*

Substances

  • Antitubercular Agents
  • Citrates
  • Glyoxylates
  • 2-methylcitric acid
  • Isocitrate Lyase
  • glyoxylic acid