Phage therapy against Pseudomonas aeruginosa infections in a cystic fibrosis zebrafish model.
Sci Rep
; 9(1): 1527, 2019 02 06.
Article
em En
| MEDLINE
| ID: mdl-30728389
ABSTRACT
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Pseudomonas aeruginosa
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Infecções por Pseudomonas
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Infecções Respiratórias
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Fagos de Pseudomonas
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Fibrose Cística
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Modelos Animais de Doenças
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Embrião não Mamífero
Limite:
Animals
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Itália