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.
Wei Li  1 ,  Andrea Sanchez-Hidalgo  1 ,  Victoria Jones  1 ,  Vinicius Calado Nogueira de Moura  1 ,  E Jeffrey North  2 ,  Mary Jackson  3
Affiliations
  • 1. Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA.
  • 2. Creighton University, School of Pharmacy & Health Professions, Department of Pharmacy Sciences, Omaha, Nebraska, USA.
  • 3. Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA [email protected].
PMID: 28115355 DOI: 10.1128/AAC.02399-16
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.
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