What is the mechanism of action of bedaquiline?

• A. ATP synthase inhibitor.
• B. Inhibits arabinosyl transferase.
• C. Inhibits DNA replication.
• D. Inhibits cell wall synthesis.

Answer: (B)

Bedaquiline works by inhibiting the mycobacterial ATP synthase enzyme, specifically blocking the proton-driven synthesis of ATP. Without ATP, the energy needed for essential processes collapses, and the bacteria die, including non-replicating persistent cells that are often hard to eradicate with other drugs. This mechanism is distinct from other anti-TB drugs: inhibitors of arabinosyl transferase (like ethambutol) disrupt cell wall polysaccharide construction; inhibitors of DNA replication (like fluoroquinolones) target DNA gyrase or related enzymes; and inhibitors of cell wall synthesis (such as isoniazid or ethionamide) block mycolic acid production. Therefore, the correct mechanism is ATP synthase inhibition, which explains bedaquiline’s role in treating multidrug-resistant TB. Note that bedaquiline requires monitoring for QT prolongation and drug interactions due to its pharmacology.