Bedaquiline, a first-in-class drug for MDR-TB, acts by a mechanism distinct from all older anti-TB drugs. Its target is:

• A DprE1 (decaprenylphosphoryl-beta-D-ribose 2'-epimerase), preventing arabinan synthesis in the cell wall
• B InhA (enoyl-ACP reductase), disrupting mycolic acid elongation in the cell wall
• C Mycobacterial ATP synthase (F-type, encoded by atpE), inhibiting proton coupling and ATP synthesis ✓
• D RNA polymerase beta subunit (rpoB), blocking mRNA chain elongation

Explanation

Bedaquiline (a diarylquinoline) specifically inhibits the c-subunit of mycobacterial ATP synthase (F1F0-type), blocking the proton pump that drives ATP synthesis. Unlike human mitochondrial ATP synthase, mycobacterial ATP synthase has a unique rotor stoichiometry and binding site, allowing selective inhibition. This mechanism is bactericidal even against metabolically dormant (non-replicating) bacilli, unlike many older drugs that require active replication. DprE1 inhibition is the mechanism of BTZ043 (benzothiazinones); InhA is isoniazid's target; rpoB is rifampicin's target.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.