The Cyclic Antibacterial Peptide Enterocin AS-48:  Isolation, Mode of Action, and Possible Food Applications

Grande, María José López; Pulido, Rubén Pérez; Aguayo, María del Carmen López; Gálvez, Antonio; Lucas, Rosario

doi:10.3390/ijms151222706

Cited by 107 publications

(58 citation statements)

References 100 publications

(131 reference statements)

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“…The IC 50 of AS-48 on promastigote proliferation is 1.3 M, a value similar to those reported for some Gram-positive bacteria (17,34,41,42) but significantly lower than many membrane-active eukaryotic peptides (9,13). AS-48 shares with many EAMPs the permeation of the cell membrane as an essential step of its bactericidal mechanism.…”

Section: Discussionsupporting

confidence: 78%

“…Thus, the higher efficacy of AS-48 than that of other EAMPs should rely on its mode of interaction with the membrane. In fact, a very low number of bacteriocin molecules is required to kill bacteria (17). How AS-48 induces membrane permeabilization is not yet fully understood.…”

Section: Discussionmentioning

confidence: 99%

“…In the last years, there has been an increasing awareness of bacteriocins as a new source of anti-infective agents (14)(15)(16), even transcending those infections from a bacterial origin (antifungal or antiviral), substantiated by their staggering structural diversity, feasibility of genetic engineering, safe use as food biopreservatives (17,18), and safe toxicity profile on higher eukaryotic cells (19). In this trend, the number of reports concerning bacteriocins as antiprotozoal agents (20)(21)(22)(23) is surprisingly lower than that of reports aiming at other eukaryotic targets such as fungi (24)(25)(26) or even tumoral cells (27)(28)(29).…”

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confidence: 99%

“…The choice of AS-48 for this goal is due to its low immunogenicity (32) and to its wide bactericidal activity on Grampositive bacteria (17,30). AS-48 is a highly compact and stable molecule (31), preserving its activity under harsh environmental conditions, as such suitable for effectiveness either inside the parasitophorous vacuole of the macrophage, where the amastigote dwells, or under tropical climate conditions.…”

mentioning

confidence: 99%

“…In addition, AS-48 does not require a cognate receptor at the target membrane, being active even on planar (33) and liposomal (34) model membranes. Furthermore, AS-48 has an excellent record in preventing human food spoilage (17). More importantly, a patent was issued for the use of AS-48 against acne and other skin bacterial infections (35), paving the way for a clinical application of this bacteriocin on the ulcers of nondisseminated cutaneous leishmaniasis.…”

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confidence: 99%

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Enterocin AS-48 as Evidence for the Use of Bacteriocins as New Leishmanicidal Agents

Abengózar

Cebrián

Saugar

et al. 2017

Antimicrob Agents Chemother

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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.

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