Bedaquiline, approved for MDR-TB, has a unique mechanism of action. Which target does it inhibit?

• A InhA (enoyl-ACP reductase) in the mycobacterial fatty acid synthesis pathway
• B Mycobacterial RNA polymerase beta subunit
• C Dihydropteroate synthase in mycobacterial folate pathway
• D Mycobacterial ATP synthase (F1F0-type, subunit c), blocking oxidative phosphorylation selectively in mycobacteria ✓

Explanation

Bedaquiline is a diarylquinoline that specifically inhibits mycobacterial F1F0 ATP synthase at the oligomeric ring of the c subunit (subunit c of the Fo component), blocking rotational catalysis and ATP synthesis. This is bactericidal against both replicating and non-replicating (dormant) mycobacteria, including MDR-TB and XDR-TB strains. Its selectivity for mycobacterial over human ATP synthase is based on structural differences. InhA is the target of isoniazid (via KatG-activated metabolite); RNA polymerase is rifampicin's target; DHPS is the sulfonamide target not relevant to TB.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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