Phage therapy is the use of phages, i.e. bacteria-specific viruses, to cure bacterial infections. In the previous project FFC#15/2021, the researchers developed a four-phage cocktail able to cure Pa infections in different infection models. However, they found that bacteria quickly acquired resistance to the cocktail and that one third of P. aeruginosa strains isolated from patients with CF were partially or completely resistant to the cocktail.
The aim of the project is to modify natural phages, already tested for the lack of potentially dangerous features, to make them able to infect and kill phage-resistant bacteria. Moreover, the researchers will assess which phages are able to kill bacteria sampled from patients in treatment with Trikafta/Kaftrio, which have never been analyzed so far in this respect.
Furthermore, phages will be tested in a pre-clinical phase for safety and effectiveness first in zebrafish, followed by studies in mice and in cultures of human bronchial epithelial cells from patients with CF.
This will represent a significant step towards introducing phage therapy among the therapeutic options of the P. aeruginosa infection for such patients. However, at the moment regulatory issues limit the application of phage therapy to compassionate treatment, i.e. to cases in which all other therapeutic options have failed. This situation is in rapid evolution, with four clinical trials ongoing for phage therapy of CF infections.