Bedaquiline, approved for multidrug-resistant tuberculosis, exerts bactericidal activity through a unique target. Which molecular target does it inhibit?

• A Mycobacterial ATP synthase (subunit c of F0F1-ATP synthase) ✓
• B Mycobacterial InhA (enoyl-ACP reductase) in mycolic acid synthesis
• C Mycobacterial RNA polymerase (RpoB subunit)
• D Mycobacterial DprE1 (decaprenylphosphoryl-β-D-ribose 2'-epimerase) in arabinogalactan synthesis

Explanation

Bedaquiline is a diarylquinoline antibiotic that specifically inhibits mycobacterial ATP synthase by binding to the c subunit (oligomeric ring) of the F0 proton pump component. This blocks the rotary mechanism of ATP synthesis without affecting mammalian mitochondrial ATP synthase, disrupting mycobacterial energy metabolism. It has bactericidal activity against both replicating and non-replicating (dormant) M. tuberculosis, including MDR-TB and XDR-TB strains. InhA is the target of isoniazid (activated); RpoB is the rifampicin target; DprE1 is the target of novel agents like BTZ-043 in development.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.