Bedaquiline is the first new anti-TB drug in 40 years and is used in multidrug-resistant TB (MDR-TB). Its mechanism differs from all existing first- and second-line drugs. It inhibits:
- A DprE1 enzyme (decaprenylphosphoryl-beta-D-ribose 2-oxidase) involved in arabinogalactan synthesis
- B Dihydrofolate reductase (DHFR), blocking folate synthesis in M. tuberculosis
- C Fatty acid synthase type I (FASI), required for mycolic acid biosynthesis
- D The proton pump component (subunit c oligomer) of mycobacterial ATP synthase (F0F1-ATPase), depleting ATP production ✓
Explanation
Bedaquiline is a diarylquinoline that specifically inhibits mycobacterial ATP synthase by binding to the c subunit of the F0 rotor component. This prevents proton translocation through the F0 portion, blocking ATP synthesis and depleting the cell of energy. It is bactericidal against both replicating and non-replicating (persistent) bacilli. The QTc prolongation observed with bedaquiline and delamanid requires cardiac monitoring and avoidance of other QT-prolonging agents. DprE1 inhibition is the mechanism of pretomanid/delamanid's arabinogalactan-synthesis component; DHFR inhibition is relevant to trimethoprim; FASI inhibition is not a standard anti-TB mechanism.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.