Opportunities for Overcoming Mycobacterium tuberculosis Drug Resistance: Emerging Mycobacterial Targets and Host-Directed Therapy

Int J Mol Sci. 2019 Jun 12;20(12):2868. doi: 10.3390/ijms20122868.

Abstract

The ever-increasing incidence of drug-resistant Mycobacterium tuberculosis infections has invigorated the focus on the discovery and development of novel treatment options. The discovery and investigation of essential mycobacterial targets is of utmost importance. In addition to the discovery of novel targets, focusing on non-lethal pathways and the use of host-directed therapies has gained interest. These adjunctive treatment options could not only lead to increased antibiotic susceptibility of Mycobacterium tuberculosis, but also have the potential to avoid the emergence of drug resistance. Host-directed therapies, on the other hand, can also reduce the associated lung pathology and improve disease outcome. This review will provide an outline of recent opportunities.

Keywords: Mycobacterium tuberculosis; antimycobacterial; drug resistance; host-directed therapy; non-lethal targets; novel targets.

Publication types

  • Review

MeSH terms

  • Animals
  • Antitubercular Agents / pharmacology*
  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Biomarkers
  • Drug Resistance, Bacterial / drug effects*
  • Host-Pathogen Interactions / drug effects*
  • Humans
  • Molecular Targeted Therapy
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / metabolism
  • Oxidation-Reduction / drug effects
  • Oxidative Phosphorylation / drug effects
  • Precision Medicine
  • Tuberculosis, Multidrug-Resistant / microbiology*

Substances

  • Antitubercular Agents
  • Bacterial Proteins
  • Biomarkers