ATP synthase inhibitor
Shuts off mycobacterial energy production at the last step
- Shuts off the energy supply of Mycobacterium tuberculosis
- Binds the c-subunit of MYCOBACTERIAL ATP synthase — proton flow stops turning the rotor
- Bactericidal even against dormant, non-replicating organisms
- Human mitochondrial synthase is spared (>10,000-fold selectivity)
- bedaquiline (SIRTURO) — MDR-TB backbone regimen
- ⚠ QT prolongation is the clinical cost (hERG peg on the ballicule)
Drugs with this mechanism (1)
- Bedaquiline — ATP-synthase inhibitor for multidrug-resistant tuberculosis; used in combination, with QT and liver monitoring.
Self-check
- Are non-replicating mycobacteria susceptible to ATP synthase inhibition here?
Yes; it is bactericidal even against dormant organisms. - What ECG adverse effect is flagged for this mechanism?
QT prolongation.
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