Inhibition of type II NADH dehydrogenase in Mycobacterium tuberculosis reveals collateral vulnerability in the electron transport chain
Ho, Vien Q T et al. “Inhibition of type II NADH dehydrogenase in Mycobacterium tuberculosisreveals collateral vulnerability in the electron transport chain.” Antimicrobial agents and chemotherapy vol. 70,11 (2026): e0075626. doi:10.1128/aac.00756-26
To sustain the anti-tuberculosis drug development pipeline, novel antibiotics must be developed both as standalone agents and as components of future combination regimens. To this end, tricyclic-spirolactams (TriSLa)-based inhibitors of mycobacterial type II NADH dehydrogenase (Ndh-2) represent a promising novel class of antibiotics, though activity is carbon source dependent. Initial studies established an enhanced understanding of the impact of TriSLa on mycobacteria using metabolomics and transcriptomics.
