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oai:repisalud.isciii.es:20.500.12105/77502024-09-27T22:52:21Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

00925njm 22002777a 4500 dc Abengózar, María Ángeles author Cebrián, Rubén author Saugar, Jose Maria author Garate, Teresa author Valdivia, Eva author Martínez-Bueno, Manuel author Maqueda, Mercedes author Rivas, Luis author 2017 We report the feasibility of enterocin AS-48, a circular cationic peptide produced by Enterococcus faecalis, as a new leishmanicidal agent. AS-48 is lethal to Leishmania promastigotes as well as to axenic and intracellular amastigotes at low micromolar concentrations, with scarce cytotoxicity to macrophages. AS-48 induced a fast bioenergetic collapse of L. donovani promastigotes but only a partial permeation of their plasma membrane with limited entrance of vital dyes, even at concentrations beyond its full lethality. Fluoresceinated AS-48 was visualized inside parasites by confocal microscopy and seen to cause mitochondrial depolarization and reactive oxygen species production. Altogether, AS-48 appeared to have a mixed leishmanicidal mechanism that includes both plasma membrane permeabilization and additional intracellular targets, with mitochondrial dysfunctionality being of special relevance. This complex leishmanicidal mechanism of AS-48 persisted even for the killing of intracellular amastigotes, as evidenced by transmission electron microscopy. We demonstrated the potentiality of AS-48 as a new and safe leishmanicidal agent, expanding the growing repertoire of eukaryotic targets for bacteriocins, and our results provide a proof of mechanism for the search of new leishmanicidal bacteriocins, whose diversity constitutes an almost endless source for new structures at moderate production cost and whose safe use on food preservation is well established. Antimicrob Agents Chemother. 2017 Mar 24;61(4). pii: e02288-16. 10.1128/AAC.02288-16 1098-6596 0066-4804 Antimicrobial agents and chemotherapy 28167557 http://hdl.handle.net/20.500.12105/7750 Antimicrobial peptide Bioenergetics Enterocin AS-48 Intracellular parasite Enterocin AS-48 as Evidence for the Use of Bacteriocins as New Leishmanicidal Agents