FFC#22/2017

In vivo validation of phage therapy against Pseudomonas aeruginosa infections using the new Zebrafish (Danio rerio) animal model

FFC#22/2017

In vivo validation of phage therapy against Pseudomonas aeruginosa infections using the new Zebrafish (Danio rerio) animal model

PRINCIPAL INVESTIGATOR

Anna Silvia Pistocchi (Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano)

RESEARCHERS

3

CATEGORY

AREA 3 Bronchopulmonary infection

DURATION

1 year

GOAL

€ 15.000 €

RESULTS

The researchers deregulated the CFTR function in zebrafish, obtaining CF embryos. They infected control (WT) and CF embryos with P. aeruginosa and compared lethality, bacterial burden and inflammatory cytokines after infection followed by phage administration. They demonstrated that phage therapy is effective against P. aeruginosa infections as it reduces lethality, bacterial burden and immune response in WT and in CF embryos. They also shew an improvement by combining the action of phages and antibiotics against P. aeruginosa infection in CF zebrafish embryos. In addition, they found that phage administration, in the absence of bacterial infection, relieves the constitutive inflammatory state of CF embryos. These data suggest promising therapeutic approaches to reduce antibiotic doses and time of administration, avoiding the development of multi-resistant P.aeruginosa isolates in a CF background.


 Pubblications

– Cafora M, Deflorian G, Forti F et al. “Phage therapy against Pseudomonas aeruginosa infections in a cystic fibrosis zebrafish model” SCI REP, submitted

Congress abstracts

– Cafora M, Forti F, Deflorian G “In vivo validation of phage therapy against Pseudomonas aeruginosa infections using zebrafish as a new model for cystic fibrosis” European Human Genetics Conference, Milan, June 16–19, 2018
– Cafora M, Forti F, Deflorian G et al. “Phage therapy against Pseudomonas aeruginosa infections in a cystic fibrosis zebrafish model” 2nd Italian Zebrafish Meeting, Pisa, Italy, 30 January – 1 February, 2019
– Cafora M, Forti F, Deflorian G et al. “Phage therapy against Pseudomonas aeruginosa infections in a cystic fibrosis zebrafish model” III Workshop Biometra, Milano, 24 settembre 2018
– Cafora M, Forti F, Deflorian G et al. “In vivo validation of phage therapy against Pseudomonas aeruginosa infections using zebrafish as a new model for cystic fibrosis” ZDM11, Leiden, The Netherlands, July 10-13, 2018

OTHER RESULTS

FFC #3/2024

Two molecules are effective in activating Heat Shock Proteins and enhancing the action of CFTR correctors with the F508del mutation in vitro.

FFC#5/2024

Some peptide nucleic acids (PNAs) re-sensitise Pseudomonas aeruginosa to the antibiotic meropenem in vitro and reduce its virulence.

FFC#1/2023

Tezacaftor, one of the components of Kaftrio, induces an accumulation of dihydroceramides both in vitro and in vivo in animal models