CFTR corrector and potentiator therapies have significantly improved the lives of many people with cystic fibrosis (CF), but some mutations remain without effective treatments. Persistent infections, especially those caused by Pseudomonas aeruginosa and Staphylococcus aureus, lead to severe lung damage. New therapeutic approaches that combine restoration of CFTR function with antimicrobial activity could simultaneously address both the genetic defect and chronic infections.

In previous studies (FFC#4/2022, FFC#8/2019, FFC#15/2017, FFC#11/2014 and FFC#14/2011), the research group identified antimicrobial peptides derived from frog skin, such as Esc(1-21) and its analogues, which are active against the major CF-related pathogens and capable of potentiating F508del-CFTR mutants. In this new project, the research will be extended to antimicrobial peptides effective against other CFTR mutations, particularly gating mutations, which impair channel opening.

The potentiating effect of the peptides on CFTR will be evaluated both individually and in synergy with existing modulators, using primary bronchial and nasal epithelial cells, obtained through FFC Ricerca Primary Culture Service.

Electrophysiological, biochemical and computational studies will be carried out to investigate peptide-CFTR interactions to uncover their mechanism of action. 

The antimicrobial activity of the peptides against Pseudomonas aeruginosa and Staphylococcus aureus will be tested in vivo in mouse models under conditions that reflect the CF lung environment.

This research could lead to multifunctional therapies able to act simultaneously on the genetic defect and infections, offering new perspectives for the treatment of cystic fibrosis.