PUBLICATION
Phage therapy against Pseudomonas aeruginosa infections in a cystic fibrosis zebrafish model
- Authors
- Cafora, M., Deflorian, G., Forti, F., Ferrari, L., Binelli, G., Briani, F., Ghisotti, D., Pistocchi, A.
- ID
- ZDB-PUB-190209-4
- Date
- 2019
- Source
- Scientific Reports 9: 1527 (Journal)
- Registered Authors
- Deflorian, Gianluca
- Keywords
- none
- MeSH Terms
-
- Animals
- Anti-Bacterial Agents/therapeutic use
- Cystic Fibrosis/complications*
- Disease Models, Animal*
- Embryo, Nonmammalian/immunology*
- Embryo, Nonmammalian/microbiology
- Embryo, Nonmammalian/virology
- Mice
- Pseudomonas Infections/immunology
- Pseudomonas Infections/microbiology
- Pseudomonas Infections/therapy*
- Pseudomonas Infections/virology
- Pseudomonas Phages/growth & development*
- Pseudomonas Phages/isolation & purification
- Pseudomonas aeruginosa/isolation & purification
- Pseudomonas aeruginosa/physiology
- Pseudomonas aeruginosa/virology*
- Respiratory Tract Infections/microbiology
- Respiratory Tract Infections/therapy*
- Zebrafish
- PubMed
- 30728389 Full text @ Sci. Rep.
Citation
Cafora, M., Deflorian, G., Forti, F., Ferrari, L., Binelli, G., Briani, F., Ghisotti, D., Pistocchi, A. (2019) Phage therapy against Pseudomonas aeruginosa infections in a cystic fibrosis zebrafish model. Scientific Reports. 9:1527.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping