Antibiotic resistance is a threat for public health, which is especially critical for cystic fibrosis patients. The study of colistin resistance has shown that bacteria become resistant because of the modification of their outer membrane, the target of colistin. The research group involved in the project has recently demonstrated that P. aeruginosa becomes resistant to colistin precisely through this mechanism. They, therefore, thought that by blocking it, the activity of the colistin would be restored. They will use as a starting point a natural compound already selected in a preliminary study. The study involves the use of colistin-resistant P. aeruginosa strains, natural compounds and their derivatives. Thanks to a combined approach of in-silico selection and biochemical modifications, derivatives of the already isolated compound will be produced and subsequently tested on different P. aeruginosa strains coming from CF patients (clinical isolates) and on small infection animal models (Galleria mellonella). From the results, further modifications can be planned to obtain compounds with characteristics suitable for use in pharmacological therapy.