Bedaquiline, a newer anti-TB drug for MDR-TB, has a unique mechanism of action compared to all traditional anti-TB agents. It targets:

• A ATP synthase (specifically the c-subunit of the FO component), depleting mycobacterial ATP and causing bacterial death ✓
• B Mycobacterial InhA (enoyl-ACP reductase) inhibiting mycolic acid synthesis
• C RNA polymerase beta subunit (rpoB), preventing transcription
• D Decaprenylphosphoryl-beta-D-ribose 2'-oxidase (DprE1) involved in arabinogalactan synthesis

Explanation

Bedaquiline is a diarylquinoline that selectively inhibits mycobacterial ATP synthase by binding to the subunit c of the F0 component. This unique mechanism exploits the fact that M. tuberculosis is uniquely dependent on ATP synthase for energy in dormant and anaerobic states — unlike mammalian cells where ATP synthase is also present but different enough to avoid toxicity. Depletion of ATP is bactericidal even in non-replicating persister organisms, addressing a major limitation of existing TB drugs. It is active against both drug-sensitive and MDR/XDR strains.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.