Evaluation of the antichagasic activity of batroxicidin, a cathelicidin-related antimicrobial peptide found in Bothrops atrox venom gland

- Batroxicidin (BatxC) has trypanocidal effect.
- BatxC was able to kill all developmental forms of Trypanosoma cruzi Y strain.
- BatxC has selectivity index of 315.
- BatxC has higher selectivity index than benznidazole.
- Necrotic mechanisms are involved in T. cruzi cell death induced by BatxC.

Antimicrobial peptides (AMPs) are potential alternatives to conventional antibiotics, as they have a fast mode of action, a low likelihood of resistance development and can act in conjunction with existing drug regimens. We report in this study the effects of batroxicidin (BatxC), a cathelicidin-related AMP from Bothrops atrox venom gland, over Trypanosoma cruzi, a protozoan that causes Chagas' disease. BatxC inhibited all T. cruzi (Y strain: benznidazole-resistant) developmental forms, with selectivity index of 315. Later, separate flow cytometry assays showed T. cruzi cell labeling by 7-aminoactinomycin D, the increase in reactive oxygen species and the loss of mitochondrial membrane potential when the parasite was treated with BatxC, which are indication of necrosis. T. cruzi cell death pathway by a necrotic mechanism was finally confirmed by scanning electron microscopy which observed loss of cell membrane integrity. In conclusion, BatxC was able to inhibit T. cruzi, with high selectivity index, by inducing necrosis.