The emergence of multidrug-resistant (MDR) microorganisms makes it increasingly difficult to treat infections. These infections include those associated with Pseudomonas aeruginosa, which is hard to eradicate, especially in patients with a compromised immune system. Naturally occurring membrane-active cationic antimicrobial peptides (CAMPs) serve as attractive candidates for the development of new therapeutic agents. Amphibian skin is one of the richest sources for such peptides, but only a few studies on their in vivo activity and mode of action were reported. Here we investigated: (i) the activity and mechanism underlying the killing of short CAMPs from frog skin (e.g., temporins and esculentin fragments) on a MDR clinical isolate of P. aeruginosa; (ii) their in vivo antimicrobial activity and mode of action, using the mini-host model of Caenorhabditis elegans. Our data revealed that in vivo, both temporin-1Tb and esculentin(1-18) were highly active in promoting the survival of pseudomonas-infected nematodes, although temporin-1Tb did not show significant activity in vitro, under the experimental conditions used. Importantly, esculentin(1-18) permeated the membrane of Pseudomonas cells inside the gut of the infected nematode. To the best of our knowledge, this is the first report showing the ability of a CAMP to permeate the microbial membrane within a living organism. Besides shedding light on a plausible mode of action in vivo of frog skin CAMPs, our data suggest that temporins and esculentins would be attractive molecules as templates for the development of new therapeutics against life-threatening infections.

Anti-pseudomonas activity of frog skin antimicrobial peptide in Caenorhabditis elegans infection model.

MANGONI, Maria Luisa;MARCELLINI HERCOLANI GADDI, LUDOVICA;UCCELLETTI, Daniela;LUCA, VINCENZO;BARRA, Donatella
2010

Abstract

The emergence of multidrug-resistant (MDR) microorganisms makes it increasingly difficult to treat infections. These infections include those associated with Pseudomonas aeruginosa, which is hard to eradicate, especially in patients with a compromised immune system. Naturally occurring membrane-active cationic antimicrobial peptides (CAMPs) serve as attractive candidates for the development of new therapeutic agents. Amphibian skin is one of the richest sources for such peptides, but only a few studies on their in vivo activity and mode of action were reported. Here we investigated: (i) the activity and mechanism underlying the killing of short CAMPs from frog skin (e.g., temporins and esculentin fragments) on a MDR clinical isolate of P. aeruginosa; (ii) their in vivo antimicrobial activity and mode of action, using the mini-host model of Caenorhabditis elegans. Our data revealed that in vivo, both temporin-1Tb and esculentin(1-18) were highly active in promoting the survival of pseudomonas-infected nematodes, although temporin-1Tb did not show significant activity in vitro, under the experimental conditions used. Importantly, esculentin(1-18) permeated the membrane of Pseudomonas cells inside the gut of the infected nematode. To the best of our knowledge, this is the first report showing the ability of a CAMP to permeate the microbial membrane within a living organism. Besides shedding light on a plausible mode of action in vivo of frog skin CAMPs, our data suggest that temporins and esculentins would be attractive molecules as templates for the development of new therapeutics against life-threatening infections.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/540618
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