Evaluation of new protease inhibitors in vitro and animal models as antivirulence therapy against Pseudomonas aeruginosa infections of Primary Ciliary Dyskinesia patients

Our research question: we aim to evaluate whether protease inhibitors can disarm P. aeruginosa, one of the most important bacterial pathogens in PCD.

 • Why is this research important? The lung environment of PCD patients and the development of bacterial resistance contribute to the increasing loss of effectiveness of antibiotics against P. aeruginosa. Hence, there is a need to identify new antibacterial strategies.

• How we will do the research: protease inhibitors will be tested to evaluate their ability to block the activity of proteases produced by P. aeruginosa. Such compounds will be also tested for their cytotoxic effects. The most active and not-cytotoxic inhibitor will be tested in an in vivo model, to evaluate its protective effect against P. aeruginosa infection/supernatant.

• What we hope to achieve: The knowledge acquired during the study will enable the development of an effective and safe protease inhibitor against P. aeruginosa, which could be used in the treatment of PCD.

• Implications for people with PCD: Persistent infections caused by  P. aeruginosa and its resistance to antibiotics pose serious threats to patients with PCD. If the selected protease inhibitor is safe and effective against P. aeruginosa, it could be used in subjects with PCD as a replacement or adjunctive therapy to antibiotics. By reducing respiratory infections and subsequent lung damage, such innovative antimicrobial therapies could help improve the quality health status of patients with PCD.

• Future prospects: To obtain a new drug anti-P. aeruginosa to be administered by aerosol in PCD patients.