Mitochondrial dysfunction induced by bedaquiline as an anti-Toxoplasma alternative

This study demonstrates that bedaquiline (BDQ), an FDA-approved diarylquinoline antimycobacterial drug for the treatment of tuberculosis, potently inhibits the tachyzoites ofT. gondii. At a safe concentration, BDQ displayed a dose-dependent inhibition onT. gondii growth with a half-maximal effective concentration (EC50) of 4.95  μM. Treatment with BDQ significantly suppressed the proliferation ofT. gondii tachyzoites in the host cell, while the invasion ability of the parasite was not affected. BDQ incubation shrunk the mitochondrial structure and decreased the mitochondrial membrane potential and ATP level ofT. gondii parasites. In addition, BDQ induced elevated ROS and led to autophagy in the parasite. By transcriptomic analysis, we found that oxidative phosphorylation pathway genes were significantly disturbed by BDQ-treated parasites. More importantly, BDQ significantly reduces brain cysts for the chronically infected mice. These results suggest that BDQ has potent anti-T. gondii activity and may impair its mitochondrial function by affecting proton transport. This study provides bedaquiline as a potential alternative drug for the treatment of toxoplasmosis, and our findings may facilitate the development of new effective drugs for the treatment of toxoplasmosis.
Source: Veterinary Research - Category: Veterinary Research Source Type: research