Bedaquiline is active against drug-resistant TB because its target is unique among anti-TB drugs. It inhibits:

• A Beta subunit of mycobacterial RNA polymerase, preventing transcription of operons essential for electron transport
• B Mycobacterial enoyl-ACP reductase (InhA), blocking mycolic acid biosynthesis like isoniazid but without requiring KatG activation
• C Decaprenyl phosphate recycling in the mycobacterial cell wall arabinogalactan assembly pathway
• D Mycobacterial ATP synthase (specifically the c-ring of the Fo subunit), blocking the proton gradient-driven ATP production essential for mycobacterial survival ✓

Explanation

Bedaquiline (diarylquinoline class) specifically inhibits mycobacterial ATP synthase, targeting the proton pump c-subunit oligomeric ring (c-ring) of the Fo motor. This prevents proton translocation and thereby ATP synthesis, which is essential for mycobacterial survival — particularly in dormant/non-replicating persister bacilli that rely on ATP synthase. This unique target means there is no cross-resistance with other anti-TB drugs. Bedaquiline also has activity against non-tuberculous mycobacteria. QT prolongation is its major toxicity, requiring ECG monitoring. Rifampicin (RNA polymerase beta) and isoniazid (InhA via KatG activation) are options A and C respectively.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.