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Phage therapy against Pseudomonas aeruginosa infections in a cystic fibrosis zebrafish model

Cystic fibrosis (CF) is a hereditary disease due to mutations in the CFTR gene and causes mortality in humans mainly due to respiratory infections caused by Pseudomonas aeruginosa. In a previous work we used phage therapy, which is a treatment with a mix of phages, to actively counteract acute P. ae...

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Autores principales: Cafora, Marco, Deflorian, Gianluca, Forti, Francesca, Ferrari, Laura, Binelli, Giorgio, Briani, Federica, Ghisotti, Daniela, Pistocchi, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365511/
https://www.ncbi.nlm.nih.gov/pubmed/30728389
http://dx.doi.org/10.1038/s41598-018-37636-x
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author Cafora, Marco
Deflorian, Gianluca
Forti, Francesca
Ferrari, Laura
Binelli, Giorgio
Briani, Federica
Ghisotti, Daniela
Pistocchi, Anna
author_facet Cafora, Marco
Deflorian, Gianluca
Forti, Francesca
Ferrari, Laura
Binelli, Giorgio
Briani, Federica
Ghisotti, Daniela
Pistocchi, Anna
author_sort Cafora, Marco
collection PubMed
description Cystic fibrosis (CF) is a hereditary disease due to mutations in the CFTR gene and causes mortality in humans mainly due to respiratory infections caused by Pseudomonas aeruginosa. In a previous work we used phage therapy, which is a treatment with a mix of phages, to actively counteract acute P. aeruginosa infections in mice and Galleria mellonella larvae. In this work we apply phage therapy to the treatment of P. aeruginosa PAO1 infections in a CF zebrafish model. The structure of the CFTR channel is evolutionary conserved between fish and mammals and cftr-loss-of-function zebrafish embryos show a phenotype that recapitulates the human disease, in particular with destruction of the pancreas. We show that phage therapy is able to decrease lethality, bacterial burden, and the pro-inflammatory response caused by PAO1 infection. In addition, phage administration relieves the constitutive inflammatory state of CF embryos. To our knowledge, this is the first time that phage therapy is used to cure P. aeruginosa infections in a CF animal model. We also find that the curative effect against PAO1 infections is improved by combining phages and antibiotic treatments, opening a useful therapeutic approach that could reduce antibiotic doses and time of administration.
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spelling pubmed-63655112019-02-08 Phage therapy against Pseudomonas aeruginosa infections in a cystic fibrosis zebrafish model Cafora, Marco Deflorian, Gianluca Forti, Francesca Ferrari, Laura Binelli, Giorgio Briani, Federica Ghisotti, Daniela Pistocchi, Anna Sci Rep Article Cystic fibrosis (CF) is a hereditary disease due to mutations in the CFTR gene and causes mortality in humans mainly due to respiratory infections caused by Pseudomonas aeruginosa. In a previous work we used phage therapy, which is a treatment with a mix of phages, to actively counteract acute P. aeruginosa infections in mice and Galleria mellonella larvae. In this work we apply phage therapy to the treatment of P. aeruginosa PAO1 infections in a CF zebrafish model. The structure of the CFTR channel is evolutionary conserved between fish and mammals and cftr-loss-of-function zebrafish embryos show a phenotype that recapitulates the human disease, in particular with destruction of the pancreas. We show that phage therapy is able to decrease lethality, bacterial burden, and the pro-inflammatory response caused by PAO1 infection. In addition, phage administration relieves the constitutive inflammatory state of CF embryos. To our knowledge, this is the first time that phage therapy is used to cure P. aeruginosa infections in a CF animal model. We also find that the curative effect against PAO1 infections is improved by combining phages and antibiotic treatments, opening a useful therapeutic approach that could reduce antibiotic doses and time of administration. Nature Publishing Group UK 2019-02-06 /pmc/articles/PMC6365511/ /pubmed/30728389 http://dx.doi.org/10.1038/s41598-018-37636-x Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Cafora, Marco
Deflorian, Gianluca
Forti, Francesca
Ferrari, Laura
Binelli, Giorgio
Briani, Federica
Ghisotti, Daniela
Pistocchi, Anna
Phage therapy against Pseudomonas aeruginosa infections in a cystic fibrosis zebrafish model
title Phage therapy against Pseudomonas aeruginosa infections in a cystic fibrosis zebrafish model
title_full Phage therapy against Pseudomonas aeruginosa infections in a cystic fibrosis zebrafish model
title_fullStr Phage therapy against Pseudomonas aeruginosa infections in a cystic fibrosis zebrafish model
title_full_unstemmed Phage therapy against Pseudomonas aeruginosa infections in a cystic fibrosis zebrafish model
title_short Phage therapy against Pseudomonas aeruginosa infections in a cystic fibrosis zebrafish model
title_sort phage therapy against pseudomonas aeruginosa infections in a cystic fibrosis zebrafish model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365511/
https://www.ncbi.nlm.nih.gov/pubmed/30728389
http://dx.doi.org/10.1038/s41598-018-37636-x
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