Affiliation:
1. Dipartimento di Biologia Cellulare e dello Sviluppo
2. Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Scienze Biochimiche A. Rossi Fanelli, Sapienza Università di Roma, Rome, Italy
Abstract
ABSTRACT
The emergence of multidrug-resistant (MDR) microorganisms makes it increasingly difficult to treat infections. These infections include those associated with
Pseudomonas aeruginosa
, which are 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
activities and modes of action have been reported. We investigated (i) the activity and mechanism underlying the killing of short CAMPs from frog skin (e.g., temporins and esculentin fragments) on an MDR clinical isolate of
P. aeruginosa
and (ii) their
in vivo
antibacterial activities and modes of action, using the minihost 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 within 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 of frog skin CAMPs
in vivo
, our data suggest that temporins and esculentins would be attractive molecules as templates for the development of new therapeutics against life-threatening infections.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
66 articles.
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