Loss-of-function mutations in ndh do not confer delamanid, ethionamide, isoniazid, or pretomanid resistance in Mycobacterium tuberculosis

Antimicrob Agents Chemother. 2024 Jan 10;68(1):e0109623. doi: 10.1128/aac.01096-23. Epub 2023 Dec 1.

Abstract

Results from clinical strains and knockouts of the H37Rv and CDC1551 laboratory strains demonstrated that ndh (Rv1854c) is not a resistance-conferring gene for isoniazid, ethionamide, delamanid, or pretomanid in Mycobacterium tuberculosis. This difference in the susceptibility to NAD-adduct-forming drugs compared with other mycobacteria may be driven by differences in the absolute intrabacterial NADH concentration.

Keywords: Mycobacterium tuberculosis; delamanid; ethionamide; isoniazid; pretomanid.

MeSH terms

  • Antitubercular Agents / pharmacology
  • Bacterial Proteins / genetics
  • Ethionamide / pharmacology
  • Humans
  • Isoniazid / pharmacology
  • Mutation
  • Mycobacterium tuberculosis* / genetics
  • Tuberculosis, Multidrug-Resistant* / microbiology

Substances

  • Isoniazid
  • Ethionamide
  • OPC-67683
  • Antitubercular Agents
  • pretomanid
  • Bacterial Proteins