Natural Polymorphisms in Mycobacterium tuberculosis Conferring Resistance to Delamanid in Drug-Naive Patients

Antimicrob Agents Chemother. 2020 Oct 20;64(11):e00513-20. doi: 10.1128/AAC.00513-20. Print 2020 Oct 20.

Abstract

Mutations in the genes of the F420 signaling pathway of Mycobacterium tuberculosis complex, including dnn, fgd1, fbiA, fbiB, fbiC, and fbiD, can lead to delamanid resistance. We searched for such mutations among 129 M. tuberculosis strains from Asia, South America, and Africa using whole-genome sequencing; 70 (54%) strains had at least one mutation in one of the genes. For 10 strains with mutations, we determined the MIC of delamanid. We found one strain from a delamanid-naive patient carrying the natural polymorphism Tyr29del (ddn) that was associated with a critical delamanid MIC.

Keywords: Mycobacterium tuberculosis; delamanid; drug resistance; mutations; natural polymorphism; resistance.

Publication types

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

MeSH terms

  • Africa
  • Antitubercular Agents / pharmacology
  • Antitubercular Agents / therapeutic use
  • Asia
  • Humans
  • Microbial Sensitivity Tests
  • Mutation / genetics
  • Mycobacterium tuberculosis* / genetics
  • Nitroimidazoles
  • Oxazoles
  • Pharmaceutical Preparations*
  • South America
  • Tuberculosis, Multidrug-Resistant* / drug therapy

Substances

  • Antitubercular Agents
  • Nitroimidazoles
  • OPC-67683
  • Oxazoles
  • Pharmaceutical Preparations