Chagas disease caused by the protozoan parasite
Trypanosoma cruzi
represents a significant public health problem in Latin America, affecting around 8 million cases worldwide. Nowadays is urgent the identification of new antichagasic agents as the only therapeutic options available, Nifurtimox and Benznidazole, are in use for >40 years, and present high toxicity, limited efficacy and frequent treatment failures in the chronic phase of the disease. Recently, it has been described the antiparasitic effect of AS-48, a bacteriocin produced by
Enterococcus faecalis
, against
Trypanosoma brucei
and
Leishmania
spp. In this work, we have demonstrated the
in vitro
potential of the AS-48 bacteriocin against
T. cruzi
. Interesting, AS-48 was more effective against the three morphological forms of different
T. cruzi
strains, and displayed lower cytotoxicity than the reference drug Benznidazole. In addition, AS-48 combines the criteria established as a potential antichagasic agent, resulting in a promising therapeutic alternative. According to the action mechanism, AS-48 trypanocidal activity could be explained in a mitochondrion-dependent manner through a reactive oxygen species production and mitochondrial depolarization, causing a fast and severe bioenergetic collapse.