I3-Ag85 effect on phthiodiolone dimycocerosate synthesis

Tuberculosis (Edinb). 2018 Jan:108:93-95. doi: 10.1016/j.tube.2017.10.007. Epub 2017 Oct 24.

Abstract

The multiplicity of drug resistant Mycobacterium tuberculosis (Mtb) strains is a growing health issue. New therapies are needed, acting on new targets. The I3-Ag85 was already reported to reduce the amount of trehalose dimycolate lipid of the mycobacterial cell wall. This inhibitor of Ag85C increased the mycobacterial wall permeability. We previously showed that M. tuberculosis strains, even multi-drug resistant and extensively-drug resistant strains, can be susceptible to vancomycin when concomitantly treated with a drug altering the cell envelope integrity. We investigated the effect of the I3-Ag85 on vancomycin susceptibility of M. tuberculosis. Although no synergy was observed, a new target of this drug was discovered: the production of phthiodiolone dimycocerosate (PDIM B).

Keywords: I3-Ag85; Mycobacterium tuberculosis; PDIM; TDM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / pharmacology*
  • Cell Wall / drug effects*
  • Cell Wall / metabolism
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Drug Synergism
  • Lipid Metabolism / drug effects*
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / metabolism
  • Mycobacterium tuberculosis / pathogenicity
  • Vancomycin / pharmacology*
  • Vancomycin Resistance / drug effects*

Substances

  • Antitubercular Agents
  • Vancomycin