Insights into Chagas treatment based on the potential of bacteriocin AS-48
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AuthorMartín-Escolano, Rubén; Cebrián, Rubén; Martín Escolano, Javier; Rosales Lombardo, María José; Maqueda Abreu, Mercedes; Sánchez Moreno, Manuel; Marín Sánchez, Clotilde
Antichagasic agentDrug discoveryTrypanosoma cruziAS-48
Martín-Escolano, R., Cebrián, R., Martín-Escolano, J., Rosales, M. J., Maqueda, M., Sánchez-Moreno, M., & Marín, C. (2019). Insights into Chagas treatment based on the potential of bacteriocin AS-48. International Journal for Parasitology: Drugs and Drug Resistance, 10, 1-8.
SponsorshipThis work was supported by the Spanish Ministry of Economy and Competitiveness [grant numbers SAF2013-48971-C2-1-R, CSD2010- 00065], both including funds from the European Regional Development Fundings (ERDF), and the Ministry of Education of Spain [RM-E, grant number FPU14/01537].
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.