Bedaquiline is used in extensively drug-resistant TB. Its mechanism of action is:

• A Inhibition of mycobacterial InhA (enoyl-ACP reductase), blocking mycolic acid synthesis
• B Activation of isoniazid-like radicals that damage mycobacterial DNA
• C Inhibition of decaprenyl-phosphate-beta-D-ribose 2-epimerase, blocking arabinogalactan synthesis
• D Inhibition of mycobacterial ATP synthase (subunit c of F-ATP synthase), depleting cellular energy ✓

Explanation

Bedaquiline is a diarylquinoline that selectively inhibits the c subunit of mycobacterial F1F0 ATP synthase. This disrupts the proton gradient and ATP synthesis, leading to energy depletion and bactericidal activity against both replicating and non-replicating (dormant) bacilli. It has no cross-resistance with existing TB drugs. InhA inhibition is the mechanism of isoniazid; arabinogalactan inhibition is the target of ethambutol.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.