Bedaquiline, approved for MDR-TB, is a novel agent that acts by:

• A Inhibiting the beta subunit of mycobacterial RNA polymerase
• B Blocking enoyl-ACP reductase (InhA), preventing mycolic acid synthesis
• C Inhibiting mycobacterial ATP synthase (specifically the c-ring of the Fo subunit), depleting cellular energy ✓
• D Inhibiting decaprenylphosphoryl-beta-D-ribose 2'-oxidase (DprE1), disrupting arabinan biosynthesis

Explanation

Bedaquiline is a diarylquinoline that specifically inhibits mycobacterial ATP synthase by binding to the c-subunit of the Fo proton pump, preventing proton translocation and ATP production. M. tuberculosis has limited capacity to synthesise ATP without functional ATP synthase, leading to bactericidal activity even against non-replicating persistent bacilli. This target is unique to mycobacteria (human ATP synthase is structurally different), explaining its selective toxicity. Resistance arises from mutations in atpE. Rifampicin inhibits RNA polymerase β; isoniazid inhibits InhA; BTZ inhibitors target DprE1.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.