The ability of P. aeruginosa to cause infection in the cystic fibrosis lung relies on its ability to use the sputum as a nutrient source for growth and to form antibiotic-resistant biofilms in this specific environment. Hence, safe drugs able to hit P. aeruginosa processes specifically required for growth and biofilm formation in the cystic fibrosis lung are highly desirable. 

A library of more than 3000 drugs already approved for their use in humans will be screened to identify molecules able to decrease P. aeruginosa adaptation to the cystic fibrosis lung. To this aim, a previously developed biosensor strain that allows monitoring bacterial growth and biofilm formation as a function of culture turbidity and light emission will be used. The screening will be performed under conditions mimicking the cystic fibrosis sputum. In this way, it will be possible to identify drugs specifically inhibiting P. aeruginosa adaptation to the cystic fibrosis lung environment. Before their translation to clinical practice in cystic fibrosis, the drugs identified in this project will require further characterization aimed at investigating their mechanism of action, activity on a large panel of clinical isolates, and efficacy in animal models of chronic lung infection.
The identified molecules will be drugs already approved for their use in humans, thus facilitating their transfer from the research laboratory to the clinical practice.
The drugs that will be identified in this project have the potential to reduce the inflammatory burden or even to eliminate P. aeruginosa infection in the cystic fibrosis lung directly, by acting as antimicrobials, or indirectly, by increasing the efficacy of conventional antibiotics. These activities are expected to improve lung functionality in cystic fibrosis patients suffering from chronic P. aeruginosa infection.
The results obtained in this project will pave the way to the development of new therapeutic options to treat chronic lung infection caused by P. aeruginosa.