Bacteriocin AS-48, a microbial cyclic polypeptide structurally and functionally related to mammalian NK-lysin

González, Carlos; Langdon, Grant M.; Bruix, Marta; Gálvez, Antonio; Valdivia, Eva; Maqueda, Mercedes; Rico, Manuel

doi:10.1073/pnas.210301097

Cited by 160 publications

(156 citation statements)

References 38 publications

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“…The fold is characterized by a globular arrangement of five ␣-helices connected by five short turn regions and enclosing a compact hydrophobic core. A very similar fold and membranolytic activity were earlier described for the linear mammalian protein NK-lysin from natural killer cells, suggesting a similar mechanism of action (26). Both NKlysin and AS-48 have exceptional stability and high resistance to temperature denaturation (3,9).…”

Section: Sequences and Structuressupporting

confidence: 63%

Structures of Naturally Occurring Circular Proteins from Bacteria

et al. 2003

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Section: Sequences and Structuressupporting

confidence: 63%

Structures of Naturally Occurring Circular Proteins from Bacteria

et al. 2003

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“…The membrane pores formed by AS-48 were unlikely to be used as a gate for intracellular entrance of new additional bacteriocin molecules in Leishmania. The reported dimensions for AS-48 pores, 2.1 nm (44) and 0.7 nm (34), will allow entrance of only monomeric forms of AS-48 (20 Å) (31). In addition, even a small molecule such as Sytox green (molecular mass, 600) showed only partial entrance in AS-48-treated parasites.…”

Section: Discussionmentioning

confidence: 99%

“…With this background in mind, we sought to investigate the leishmanicidal activity of AS-48, a 70-residue circular bacteriocin (molecular mass, 7.149 kDa), highly cationic (pI ϭ 10.09) and with an amphipatic structure (30,31). 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).…”

mentioning

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. 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.…”

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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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“…25 Additionally, several class IIb (i.e., two-component) bacteriocins, such as lactococcin G and plantaricin E/F, are isolated from LAB. 27 Fewer bacteriocins of other types have been isolated from LAB, although circular bacteriocins (e.g., enterocin AS-48, carnocyclin A) 66,67 and leaderless bacteriocins (e.g., lacticin Q, enterocins 7A, and 7B) 68,69 have all been described. Unlike bacilli and paenibacilli, LAB tend not to produce antibacterial nonribosomal peptides.…”

Section: Antimicrobial Peptides Active Against C Jejuni From Labmentioning

confidence: 99%

Characterization of bacterial antimicrobial peptides active against Campylobacter jejuni

Lohans

Belkum

et al. 2015

Can. J. Chem.

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Abstract:Campylobacter jejuni is one of the major causes of food poisoning, often resulting from the consumption of improperly cooked poultry products. The emergence of C. jejuni strains resistant to conventional antibiotics necessitates the evaluation of other possible treatments or preventative measures to minimize the impact and prevalence of infections. Antimicrobial peptides produced by bacteria have begun to emerge as a potential means of decreasing the levels of C. jejuni in poultry, thereby limiting Campylobacter contamination in associated food products. A number of bacteriocins produced by Gram-positive bacteria have unexpectedly been described as having antimicrobial activity against the Gram-negative C. jejuni. Additionally, some nonribosomal lipopeptides produced by Bacillus and Paenibacillus spp. show efficacy against this pathogen. This review will describe the bacterial antimicrobial peptides reported to be active against C. jejuni, with an emphasis on the characterization of their primary structures. However, for many of these peptides, little is known about their amino acid sequences and structures. Furthermore, there are unusual inconsistencies associated with the reported amino acid sequences for several of the more well-studied bacteriocins. Clarifying the chemical nature of these promising antimicrobial peptides is necessary before their potential utility for livestock protection from C. jejuni can be fully explored. Once these peptides are better characterized, they may prove to be strong candidates for minimizing the impact of Campylobacter on human health.Key words: Campylobacter, bacteriocin, antimicrobial, lipopeptide, tridecaptin. Résumé :Campylobacter jejuni est l'un des agents les plus importants à l'origine de l'empoisonnement alimentaire, souvent dû à la consommation de produits de volaille cuits de manière inadéquate. L'émergence de souches de C. jejuni résistantes aux antibiotiques habituels exige d'évaluer les autres possibilités de traitements ou mesures préventives afin de réduire la préva-lence et les conséquences des infections. La possibilité d'utiliser les peptides antimicrobiens d'origine bactérienne pour diminuer les taux de C. jejuni dans la volaille et limiter ainsi la contamination des produits alimentaires dérivés par le Campylobacter est apparue récemment. De façon inattendue, un certain nombre de bactériocines produites par des bactéries à Gram positif ont été décrites comme ayant une activité antimicrobienne contre la bactérie à Gram négatif C. jejuni. De plus, certains lipopeptides d'origine non ribosomique produits par des espèces de Bacillus et Paenibacillus montrent une efficacité contre cet agent pathogène. Cet exposé de synthèse décrira les peptides antimicrobiens d'origine bactérienne dont l'activité contre C. jejuni est connue, et mettra l'accent sur la caractérisation de leur structure primaire. Cependant, on sait peu de choses de la séquence d'acides aminés et de la structure de plusieurs de ces peptides. En outre, les séquences d'acides aminés de plusi...

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Bacteriocin AS-48, a microbial cyclic polypeptide structurally and functionally related to mammalian NK-lysin

Cited by 160 publications

References 38 publications

Structures of Naturally Occurring Circular Proteins from Bacteria

Structures of Naturally Occurring Circular Proteins from Bacteria

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

Characterization of bacterial antimicrobial peptides active against Campylobacter jejuni

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