Bedaquiline (BDQ) is used in drug-resistant TB. Its mechanism of action is unique among anti-TB drugs because it:
- A Intercalates into mycobacterial DNA and inhibits RNA polymerase β-subunit (rpoB) analogous to rifampicin
- B Inhibits the ATP synthase (FO-F1 type) of Mycobacterium tuberculosis specifically, blocking ATP synthesis in both aerobic and anaerobic (persistent) bacilli ✓
- C Blocks mycolic acid synthesis by inhibiting the InhA enoyl-ACP reductase with a similar mechanism to isoniazid
- D Inhibits decaprenyl phosphate recycling, blocking arabinogalactan synthesis like ethambutol
Explanation
Bedaquiline is a diarylquinoline that specifically inhibits the mycobacterial F1FO-ATP synthase (atpE subunit of the c-ring). This is highly mycobacteria-specific because the binding site on mycobacterial c-subunit differs from mammalian mitochondrial ATP synthase. Critically, bedaquiline remains bactericidal against both actively replicating bacilli (requiring ATP for growth) and metabolically dormant persisters (which require ATP for maintenance of membrane integrity), explaining its activity in drug-tolerant TB. It has a very long half-life (~5.5 months) due to tissue sequestration, enabling weekly dosing later in treatment. QTc prolongation is its major adverse effect, requiring ECG monitoring.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.