Background. Early aggressive and maintenance antibiotic therapies prolong cystic fibrosis (CF) patient life, but are not able to eradicate Pseudomonas aeruginosa lung infection. Anti-virulence drugs represent a promising therapeutic option in CF. These drugs could alleviate the severity of the infection, reduce lung inflammation, and help antibiotics in eradicating the P. aeruginosa infection. The long times and high costs required for the development of “brand new” anti-virulence drugs can be saved by repurposing “old” drugs already used in humans for different diseases. We have recently shown that the antimycotic drug flucytosine and the anthelmintic drug niclosamide can be repurposed to suppress P. aeruginosa virulence in vitro and in animal models of infection. However, the old drugs need to be re-formulated for the new application in CF therapy.

Hypothesis and objectives. 1) To develop and validate inhalable formulations of flucytosine and niclosamide for CF therapy. 2) To discovery additional drugs with anti-virulence activity against P. aeruginosa.