Autophagic-related cell death of Trypanosoma brucei induced by bacteriocin AS-48

Publication date: August 2018Source: International Journal for Parasitology: Drugs and Drug Resistance, Volume 8, Issue 2Author(s): Marta Martínez-García, Jean-Mathieu Bart, Jenny Campos-Salinas, Eva Valdivia, Manuel Martínez-Bueno, Elena González-Rey, Miguel Navarro, Mercedes Maqueda, Rubén Cebrián, José M. Pérez-VictoriaAbstractThe parasitic protozoan Trypanosoma brucei is the causative agent of human African trypanosomiasis (sleeping sickness) and nagana. Current drug therapies have limited efficacy, high toxicity and/or are continually hampered by the appearance of resistance. Antimicrobial peptides have recently attracted attention as potential parasiticidal compounds. Here, we explore circular bacteriocin AS-48's ability to kill clinically relevant bloodstream forms of T. brucei gambiense, T. brucei rhodesiense and T. brucei brucei. AS-48 exhibited excellent anti-trypanosomal activity in vitro (EC50 = 1–3 nM) against the three T. brucei subspecies, but it was innocuous to human cells at 104-fold higher concentrations. In contrast to its antibacterial action, AS-48 does not kill the parasite through plasma membrane permeabilization but by targeting intracellular compartments. This was evidenced by the fact that vital dye internalization-prohibiting concentrations of AS-48 could kill the parasite at 37 °C but not at 4 °C. Furthermore, AS-48 interacted with the surface of the parasite, at least in part via VSG, its uptake was temperature-dependent and...
Source: International Journal for Parasitology: Drugs and Drug Resistance - Category: Parasitology Source Type: research