In vivo therapeutic efficacy of frog skin-derived peptides against Pseudomonas aeruginosa-induced pulmonary infection

Abstract Pseudomonas aeruginosa is an opportunistic and frequently drug-resistant pulmonary pathogen especially in cystic fibrosis sufferers. Recently, the frog skin-derived antimicrobial peptide (AMP) Esc(1–21) and its diastereomer Esc(1–21)-1c were found to possess potent in vitro antipseudomonal...

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Autores principales:	Chen Chen, Maria Luisa Mangoni, Y. Peter Di
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/68bccc7475c24d24b7ed3e1ce73fc79e
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spelling	oai:doaj.org-article:68bccc7475c24d24b7ed3e1ce73fc79e2021-12-02T16:08:22ZIn vivo therapeutic efficacy of frog skin-derived peptides against Pseudomonas aeruginosa-induced pulmonary infection10.1038/s41598-017-08361-82045-2322https://doaj.org/article/68bccc7475c24d24b7ed3e1ce73fc79e2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08361-8https://doaj.org/toc/2045-2322Abstract Pseudomonas aeruginosa is an opportunistic and frequently drug-resistant pulmonary pathogen especially in cystic fibrosis sufferers. Recently, the frog skin-derived antimicrobial peptide (AMP) Esc(1–21) and its diastereomer Esc(1–21)-1c were found to possess potent in vitro antipseudomonal activity. Here, they were first shown to preserve the barrier integrity of airway epithelial cells better than the human AMP LL-37. Furthermore, Esc(1–21)-1c was more efficacious than Esc(1–21) and LL-37 in protecting host from pulmonary bacterial infection after a single intra-tracheal instillation at a very low dosage of 0.1 mg/kg. The protection was evidenced by 2-log reduction of lung bacterial burden and was accompanied by less leukocytes recruitment and attenuated inflammatory response. In addition, the diastereomer was more efficient in reducing the systemic dissemination of bacterial cells. Importantly, in contrast to what reported for other AMPs, the peptide was administered at 2 hours after bacterial challenge to better reflect the real life infectious conditions. To the best of our knowledge, this is also the first study investigating the effect of AMPs on airway-epithelia associated genes upon administration to infected lungs. Overall, our data highly support advanced preclinical studies for the development of Esc(1–21)-1c as an efficacious therapeutic alternative against pulmonary P. aeruginosa infections.Chen ChenMaria Luisa MangoniY. Peter DiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chen Chen Maria Luisa Mangoni Y. Peter Di In vivo therapeutic efficacy of frog skin-derived peptides against Pseudomonas aeruginosa-induced pulmonary infection
description	Abstract Pseudomonas aeruginosa is an opportunistic and frequently drug-resistant pulmonary pathogen especially in cystic fibrosis sufferers. Recently, the frog skin-derived antimicrobial peptide (AMP) Esc(1–21) and its diastereomer Esc(1–21)-1c were found to possess potent in vitro antipseudomonal activity. Here, they were first shown to preserve the barrier integrity of airway epithelial cells better than the human AMP LL-37. Furthermore, Esc(1–21)-1c was more efficacious than Esc(1–21) and LL-37 in protecting host from pulmonary bacterial infection after a single intra-tracheal instillation at a very low dosage of 0.1 mg/kg. The protection was evidenced by 2-log reduction of lung bacterial burden and was accompanied by less leukocytes recruitment and attenuated inflammatory response. In addition, the diastereomer was more efficient in reducing the systemic dissemination of bacterial cells. Importantly, in contrast to what reported for other AMPs, the peptide was administered at 2 hours after bacterial challenge to better reflect the real life infectious conditions. To the best of our knowledge, this is also the first study investigating the effect of AMPs on airway-epithelia associated genes upon administration to infected lungs. Overall, our data highly support advanced preclinical studies for the development of Esc(1–21)-1c as an efficacious therapeutic alternative against pulmonary P. aeruginosa infections.
format	article
author	Chen Chen Maria Luisa Mangoni Y. Peter Di
author_facet	Chen Chen Maria Luisa Mangoni Y. Peter Di
author_sort	Chen Chen
title	In vivo therapeutic efficacy of frog skin-derived peptides against Pseudomonas aeruginosa-induced pulmonary infection
title_short	In vivo therapeutic efficacy of frog skin-derived peptides against Pseudomonas aeruginosa-induced pulmonary infection
title_full	In vivo therapeutic efficacy of frog skin-derived peptides against Pseudomonas aeruginosa-induced pulmonary infection
title_fullStr	In vivo therapeutic efficacy of frog skin-derived peptides against Pseudomonas aeruginosa-induced pulmonary infection
title_full_unstemmed	In vivo therapeutic efficacy of frog skin-derived peptides against Pseudomonas aeruginosa-induced pulmonary infection
title_sort	in vivo therapeutic efficacy of frog skin-derived peptides against pseudomonas aeruginosa-induced pulmonary infection
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/68bccc7475c24d24b7ed3e1ce73fc79e
work_keys_str_mv	AT chenchen invivotherapeuticefficacyoffrogskinderivedpeptidesagainstpseudomonasaeruginosainducedpulmonaryinfection AT marialuisamangoni invivotherapeuticefficacyoffrogskinderivedpeptidesagainstpseudomonasaeruginosainducedpulmonaryinfection AT ypeterdi invivotherapeuticefficacyoffrogskinderivedpeptidesagainstpseudomonasaeruginosainducedpulmonaryinfection
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In vivo therapeutic efficacy of frog skin-derived peptides against Pseudomonas aeruginosa-induced pulmonary infection

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