Bedaquiline, a WHO Group B drug for MDR-TB, has a novel mechanism of action. Which statement correctly describes it?

• A It inhibits mycobacterial RNA polymerase, preventing transcription of essential genes
• B It inhibits cell wall arabinan polymerization by blocking arabinosyl transferase
• C It inhibits InhA (enoyl-ACP reductase), blocking mycolic acid synthesis
• D It inhibits the mycobacterial ATP synthase (subunit c of F1F0-ATP synthase), disrupting energy production ✓

Explanation

Bedaquiline (a diarylquinoline) is the first truly novel anti-TB drug in 40 years. It selectively inhibits the c-subunit of mycobacterial F1F0-ATP synthase (specifically the atpE gene product), disrupting the proton pump required for ATP synthesis. This causes ATP depletion in both actively replicating and dormant ('persistor') bacilli. Its activity against non-replicating persisters is a key advantage in shortening treatment duration. RNA polymerase is inhibited by rifampicin; arabinosyl transferase by ethambutol; InhA by isoniazid and ethionamide.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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