In cystic fibrosis (CF), lung infections caused by the bacterium Pseudomonas aeruginosa are difficult to eliminate because this bacterium exploits the mucus present in CF lungs to grow, produce virulence factors and form antibiotic-resistant biofilms.
For this reason, it is important to identify drugs that are effective in inhibiting these processes in such a special environment as the CF lung. In this project, the researchers wondered whether drugs used to treat other diseases in humans could also be used to combat chronic lung infections caused by P. aeruginosa in people with CF.

The researchers used a growth medium similar to the lung sputum of people with CF, called SCFM, synthetic CF sputum medium.  On the SCFM they cultivated a genetically modified variant of P. aeruginosa (called biosensor) that allows them to identify molecules with anti-virulence or anti-biofilm activity. Clinical isolates of P. aeruginosa were also used. A library of over 3000 US FDA-approved drugs was also selected.
The researchers used the biosensor variant to understand whether drugs belonging to the compound library could inhibit the growth, virulence or biofilm formation of P. aeruginosa in SCFM medium. 

The most promising molecules identified during this screening phase were further characterised in vitro for their potential antimicrobial, anti-virulence or anti-biofilm activities on laboratory variants and clinical isolates of P. aeruginosa.
Some of the drugs tested showed promise in inhibiting P. aeruginosa growth, virulence or its ability to form biofilms. These molecules are active in the medium that mimics lung sputum and also act against variants of P. aeruginosa isolated from the lungs of people with CF.

The identified drugs need to be further characterised but lay the groundwork for the development of new treatments for lung infections caused by P. aeruginosa in people with CF.

Publications

• Weimann A, Dinan AM et al. Evolution and host-specific adaptation of Pseudomonas aeruginosa. Science, 2024 385(6704):eadi0908.
• Caruso L, Mellini M et al. Hydrogen sulfide production does not affect antibiotic resistance in Pseudomonas aeruginosa. Antimicrobial Agents and Chemotherapy, 2024. 68(4):e0007524

Abstracts submitted to scientific conferences

• Drug repurposing to inhibit Pseudomonas aeruginosa adaptation to the CF lung environment. Cortona Procarioti, Cortona, Italy, 27-29 June 2024
• Drug repurposing to inhibit Pseudomonas aeruginosa adaptation to the cystic fibrosis lung environment. Flagship Project 7 Mid-term Plenary Workshop, Rome, Italy, 13 June 2024
• Drug repurposing to inhibit Pseudomonas aeruginosa adaptation to the CF lung environment. XIII Congress of Microbiologists of Serbia, Belgrado, Serbia, 4-6 April 2024
• Set up of a whole-cell biosensor-based screening system to identify molecules inhibiting Pseudomonas aeruginosa growth or pathogenicity in the lung of individuals with cystic fibrosis. EureStop COST Action General Meeting, Rome, Italy, 21-22 March 2024