Synergistic Interactions of MmpL3 Inhibitors with Antitubercular Compounds In Vitro

Antimicrob Agents Chemother. 2017 Mar 24;61(4):e02399-16. doi: 10.1128/AAC.02399-16. Print 2017 Apr.

Abstract

A number of inhibitors of the essential Mycobacterium tuberculosis mycolic acid transporter, MmpL3, are currently under development as potential novel antituberculosis agents. Using the checkerboard method to study the interaction profiles of various antituberculosis drugs or experimental compounds with two different chemotypes inhibiting this transporter (indolcarboxamides and adamantyl ureas), we showed that MmpL3 inhibitors act synergistically with rifampin, bedaquiline, clofazimine, and β-lactams.

Keywords: MmpL3; Mycobacterium; Mycobacterium tuberculosis; drug synergism; mycolic acids; tuberculosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / pharmacology*
  • Clofazimine / pharmacology
  • Diarylquinolines / pharmacology
  • Drug Synergism
  • Membrane Transport Proteins / metabolism*
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / metabolism
  • Mycolic Acids / metabolism
  • Rifampin / pharmacology
  • beta-Lactams / pharmacology

Substances

  • Antitubercular Agents
  • Diarylquinolines
  • Membrane Transport Proteins
  • Mycolic Acids
  • beta-Lactams
  • bedaquiline
  • Clofazimine
  • Rifampin