Cafora M, Deflorian G, Forti F et al. Phage therapy against Pseudomonas aeruginosa infections in a cystic fibrosis zebrafish model // Scientific Reports 2019, 9, Article number: 1527. https://doi.org/10.1038/s41598-018-37636-x
Using a freshwater fish model of cystic fibrosis (CF), researchers saw that a combination of bacteriophages and antibiotics is effective against the disease.
Lung infection with Pseudomonas aeruginosa bacteria is the main cause of death among CF patients. With current antibiotics failing to protect against hard-to-treat bacteria, the need for alternative therapies is high.
In a recent study, researchers described a cocktail of bacteriophages — viruses that naturally infect bacteria — that was effective against P. aeruginosa in two animal models of acute infection. Now, researchers tested how a similar approach would work in a freshwater zebrafish model of CF. Although an animal model without lungs might not seem to be best to test a treatment against CF, zebrafish genetically modified to lack the CFTR gene (the gene defective in CF) have a very similar disease manifestation as humans. The genetic sequence of CFTR is quite similar among species.
In the study, researchers infected zebrafish embryos and verified that fluorescently labeled bacteria rapidly spread to the whole embryo. The infection caused the death of at least 50% of the embryos 20 hours post-infection. As expected, embryos with CF were more susceptible to bacterial infection, and presented significantly increased mortality compared with normal embryos.
Phage therapy against P. aeruginosa infection was administered to both control and CF embryos, and the team observed a significant reduction of lethality — a mean decrease of 66% to 35% for controls, and 83% to 52% for CF embryos.
When researchers tested a combined treatment of phages with the antibiotic ciprofloxacin, they saw an even lower death rate in comparison to embryos treated with only phages or the antibiotic.
Overall, the results showed that “phage therapy is able to decrease lethality, bacterial burden, and the pro-inflammatory response caused by [Pseudomonas aeruginosa] infection,” researchers stated.
The data also suggested that “phage therapy and antibiotic administration appears as a promising therapeutic approach, especially in order to reduce antibiotic doses and treatment duration,” the team concluded.