A patient with rifampicin-resistant tuberculosis is started on a regimen containing bedaquiline. The mechanism of bedaquiline is:

• A Inhibits mycobacterial F0F1-ATP synthase, preventing ATP synthesis and causing bactericidal activity ✓
• B Inhibits mycobacterial DprE1, blocking arabinogalactan cell wall synthesis
• C Inhibits 23S rRNA methylation, disrupting 50S ribosomal assembly in mycobacteria
• D Inhibits mycobacterial RNA polymerase beta subunit at a binding site distinct from rifampicin

Explanation

Bedaquiline is a diarylquinoline approved for MDR-TB and XDR-TB. It selectively inhibits mycobacterial ATP synthase (specifically the Fo subunit c-ring) at a site not homologous to the mammalian enzyme, providing selectivity. ATP synthase is essential for oxidative phosphorylation in mycobacteria; its inhibition depletes ATP stores and is bactericidal against both replicating and non-replicating (persister) bacilli. DprE1 inhibition is the mechanism of pretomanid and TBA-354. Linezolid inhibits 23S rRNA peptidyl transferase. Rifampicin/rifabutin target RNA polymerase β-subunit.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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