What is the mechanism of action of bedaquiline?

• A. Inhibits mycobacterial ATP synthase, depleting energy production.
• B. Inhibits cell wall synthesis
• C. Inhibits protein synthesis
• D. Inhibits DNA replication

Answer: (A)

Bedaquiline works by inhibiting the mycobacterial ATP synthase, the enzyme that makes ATP. By blocking ATP production, the bacterium loses its usable energy, which stops growth and leads to death. This energy-focused mechanism is unique among TB drugs and is effective against both actively growing bacteria and some nonreplicating forms that rely on ATP generation for survival. Bedaquiline binds specifically to the c subunit of ATP synthase (AtpE) in Mycobacterium tuberculosis, providing selective bacterial activity and making it valuable in drug-resistant TB regimens, though it carries risks like QT prolongation and drug interactions.

Other mechanisms target different bacterial processes—cell wall synthesis, protein synthesis, or DNA replication—but bedaquiline’s action disrupts energy production rather than these other essential pathways.