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PASTEUR INSTITUTE SEMINAR SERIES How to squash the “superbug” Pseudomonas aeruginosa? A lesson from the amphibian skin-derived Esculentin(1-21) and its diastereomer Prof. Maria Luisa Mangoni Giovedì 18 Gennaio, ore 14:00 presso l'Aula Magna Viale Regina Elena 295 Dip Scienze Biochimiche "A. Rossi Fanelli" Sapienza Università e Istituto Pasteur italia The alarming rise of antibiotic-resistant “superbugs” represents an increasingly serious threat to global public health. Among microbial pathogens for which new anti-infective agents are urgently needed there is the Gram-negative bacterium Pseudomonas aeruginosa. We discovered that the frog skin-derived cationic antimicrobial peptide Esc(1-21) has (i) rapid killing kinetics against both free- living and biofilm forms of P. aeruginosa, with membrane-perturbing activity as a plausible mode of action which limits the emergence of resistance; (ii) the capability to reduce bacterial load within the lungs or the cornea of murine models of Pseudomonas-induced pneumonia or keratitis, respectively; (iii) the ability to stimulate migration of bronchial epithelial cells and, as a result, presumably to accelerate the recovery of an injured bronchial epithelium. Furthermore, a diastereomer of Esc(1-21), containing two D-amino acids was found to be less cytotoxic; more stable and with a better in vivo efficacy. We also demonstrated that conjugation of Esc(1-21) to gold-nanoparticles significantly increases the microbicidal activity of the peptide without being harmful to mammalian cells. Overall, these peptides represent attractive alternatives for local treatment of Pseudomonas-associated infections. per informazioni: [email protected]

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BIOL

GDEGLI EUCARIOTI

M

DI INTERESSE B

BIOLOGIA MOLECOLARE

M

GDEGLI EUCARIOTI

M

DI INTERESSE B

PASTEUR INSTITUTE SEMINAR SERIES

w

How to squash the “superbug” Pseudomonas aeruginosa? A lesson from the

amphibian skin-derived Esculentin(1-21) and its diastereomer

Prof. Maria Luisa Mangoni

Giovedì 18 Gennaio, ore 14:00

presso l'Aula Magna Viale Regina Elena 295

Dip Scienze Biochimiche "A. Rossi Fanelli" Sapienza Università e Istituto Pasteur italia

The alarming rise of antibiotic-resistant “superbugs” represents an increasingly serious threat to global public health. Among microbial pathogens for which new

anti-infective agents are urgently needed there is the Gram-negative bacterium Pseudomonas aeruginosa. We discovered that the frog skin-derived cationic

antimicrobial peptide Esc(1-21) has (i) rapid killing kinetics against both free-living and biofilm forms of P. aeruginosa, with membrane-perturbing activity as a

plausible mode of action which limits the emergence of resistance; (ii) the capability to reduce bacterial load within the lungs or the cornea of murine models

of Pseudomonas-induced pneumonia or keratitis, respectively; (iii) the ability to stimulate migration of bronchial epithelial cells and, as a result, presumably to

accelerate the recovery of an injured bronchial epithelium. Furthermore, a diastereomer of Esc(1-21), containing two D-amino acids was found to be less cytotoxic; more stable and with a better in vivo efficacy. We also demonstrated that conjugation of Esc(1-21) to gold-nanoparticles significantly increases the microbicidal activity of the peptide without being harmful to mammalian cells. Overall, these peptides represent attractive alternatives for local treatment of

Pseudomonas-associated infections.

per informazioni: [email protected]