Bedaquiline is a novel anti-TB drug effective against MDR-TB. Its target is distinct from all traditional anti-TB drugs. What is its mechanism?

• A Inhibits mycobacterial ATP synthase (subunit c of F0F1-ATP synthase), depleting ATP and killing both actively replicating and dormant bacilli ✓
• B Inhibits enoyl-ACP reductase (InhA), blocking mycolic acid synthesis
• C Inhibits RNA polymerase beta subunit encoded by rpoB gene
• D Inhibits decaprenylphosphoryl-beta-D-ribose oxidase (DprE1), blocking arabinogalactan synthesis

Explanation

Bedaquiline is a diarylquinoline that specifically inhibits the mycobacterial ATP synthase by binding to subunit c of the F0F1-ATPase. This blocks proton translocation coupled to ATP synthesis, rapidly depleting intracellular ATP. Critically, it is bactericidal against both replicating and non-replicating (dormant/persister) bacilli because persisters still require ATP for maintenance. This activity against persisters is essential for shortening treatment duration. Because the human mitochondrial ATP synthase differs structurally, bedaquiline has high selectivity. QTc prolongation is the 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.