Pseudomonas aeruginosa (Pa) infections are a major cause of lung damage in cystic fibrosis. Conventional antibiotics are often ineffective due to both antibiotic resistance and the bacterium’s ability to form biofilms —protective barriers that make it even harder to eradicate. An alternative strategy is to inhibit the production of virulence factors, thereby reducing the pathogen’s ability to cause infection and consequently lung damage. 

The ApaH protein has been recently identified as a promising target for the development of anti-virulence drugs against Pa: in fact, its inactivation drastically reduces the production of several virulence factors and decreases bacterium’s infectivity in experimental models.

In this project, researchers will use bioinformatic, structural, and biochemical methods to identify druggable sites on the ApaH protein. Next, a virtual screening will be performed based on the obtained protein structure to identify potential inhibitors. Finally, they will validate the activity of the selected compounds against the purified ApaH protein and against Pa reference strains and cystic fibrosis isolates.

If successful, this research will set the stage for further development and preclinical testing of ApaH inhibitors, with the long-term goal of developing new anti-virulence drugs to improve cystic fibrosis infection management.