Thanks to the collaboration of researchers with complementary skills in the fields of immunology, biochemistry, and pharmaceutical chemistry, the project has led to the identification of molecules potentially able to enhance the immune defenses of the CF patient and to reduce the fungi pathogenicity. This double action derives from the ability of these molecules to bind to the same enzyme, both in the host and in the microorganism, involved in the metabolism of a specific class of lipids, called sphingolipids. These molecules inhibit the activity of the enzyme causing an increase in the levels of a molecule called sphingosine-1-phosphate (S1P). Based on previous evidence in the literature, confirmed and extended by our results, the increase in S1P in the host enhances the body’s defenses. On the contrary, the increase in S1P in fungi is toxic to the microorganism. The project was carried out along two main lines: on the one hand, using bioinformatics tools for the identification of molecules with a dual action on the host and fungal enzyme; on the other hand, through the development of all the necessary tools to evaluate the efficacy of the identified molecules, which include the purified enzymes of both the host and the fungus, in vitro culture systems of both the fungus alone and bronchial epithelial cells of CF patients infected with the fungus, and in vivo models of CF mice. The molecules identified by this study represent the basis for the future development of drugs, whose importance in the therapy of CF patients is twofold: first, to reduce the chronic inflammatory state that characterizes the lungs of CF patients and, at the same time, to prevent or protect against the development of fungal infections; second, to reduce the therapeutic burden thanks to the use of a single drug with multiple beneficial actions on the CF patient.