Simultaneous Inhibition of Cytochrome bd Oxidase and ATP Synthase for Complete Eradication of Mycobacterium tuberculosis - PubMed
4 hours ago
- #Synergistic Therapy
- #Drug Resistance
- #Mycobacterium tuberculosis
- Bedaquiline (BDQ), an ATP synthase inhibitor used for MDR-TB, has limitations like delayed killing and resistance due to metabolic heterogeneity and electron transport chain redundancy.
- Simultaneously inhibiting cytochrome bd oxidase (Cyt-bd) and ATP synthase leads to synergistic, rapid bactericidal activity, with complete clearance of Mycobacterium tuberculosis in 12 days.
- Cyt-bd inhibitor ND-011992 blocks respiratory redundancy under BDQ pressure, causing severe ATP depletion and oxygen consumption arrest, effective even against nonreplicating and intracellular bacteria.
- This combination validates Cyt-bd as a key target and offers a sterilizing regimen to overcome drug tolerance in TB therapy.