Pseudomonas aeruginosa infection is particularly serious in people with cystic fibrosis (pxCF). Indeed, Pa is able to persist for years in the respiratory tract due to its ability to form a biofilm, inaccessible to the host immune cells and antibiotics. In vitro biofilm model systems do not properly mimic the natural environment of the CF lung, such as real reproduction of bacterial physiology and biofilm architecture, therefore limiting the discovery of novel therapies for CF infection.
Bacteriophages (phages), viruses that infect bacteria, represent a suitable strategy to counteract P. aeruginosa infection in the CF context. The positive outcome obtained in vertebrate and invertebrate models encourages further investigation of phage therapy effects.
In this project the researchers propose the use of a new cystic fibrosis model, the ex vivo pig lung (EVPL), to study Pseudomonas aeruginosa infections and apply the phage therapy as an antimicrobial agent.
The EVPL model is able to better recapitulate the environment of the human CF airways and it can be used to study the bronchial tissue-associated biofilm, thus allowing to test the antimicrobial agents effects on the biofilm normally affecting CF lungs. Different strains of Pa will be used, such as those derived from laboratory, clinical, or pwCF treated with CFTR modulators and the reduction of the bacterial growth after the administration of phages will be assessed. In addition, phages will be combined with antibiotics, to promote new therapeutic approaches in order to reduce antibiotic doses and time of administration, avoid the development of antibiotic-resistant strains, or to better eradicate biofilm.