Mycolic acids: deciphering and targeting the Achilles' heel of the tubercle bacillus

Mol Microbiol. 2015 Oct;98(1):7-16. doi: 10.1111/mmi.13101. Epub 2015 Jul 30.

Abstract

Mycolic acids are unique long chain fatty acids found in the lipid-rich cell walls of mycobacteria including the tubercle bacillus Mycobacterium tuberculosis. Essential for viability and virulence, enzymes involved in the biosynthesis of mycolic acids represent novel targets for drug development. This is particularly relevant to the impact on global health given the rise of multidrug resistant and extensively drug resistant strains of M. tuberculosis. In this review, we discuss recent advances in our understanding of how mycolic acid are synthesised, especially the potential role of specialised fatty acid synthase complexes. Also, we examine the role of a recently reported mycolic acid transporter MmpL3 with reference to several reports of the targeting of this transporter by diverse compounds with anti-M. tuberculosis activity. Additionally, we consider recent findings that place mycolic acid biosynthesis in the context of the cell biology of the bacterium, viz its localisation and co-ordination with the bacterial cytoskeleton, and its role beyond maintaining cell envelope integrity.

Publication types

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

MeSH terms

  • Antitubercular Agents / pharmacology
  • Bacterial Proteins / metabolism
  • Drug Discovery
  • Fatty Acid Synthases / metabolism
  • Membrane Transport Proteins / metabolism
  • Mycobacterium tuberculosis / chemistry*
  • Mycobacterium tuberculosis / enzymology
  • Mycobacterium tuberculosis / metabolism*
  • Mycobacterium tuberculosis / pathogenicity
  • Mycolic Acids / chemistry
  • Mycolic Acids / metabolism*
  • Tuberculosis / drug therapy
  • Tuberculosis / microbiology
  • Virulence

Substances

  • Antitubercular Agents
  • Bacterial Proteins
  • Membrane Transport Proteins
  • MmpL3 protein, Mycobacterium tuberculosis
  • Mycolic Acids
  • Fatty Acid Synthases