Colistin is an antibiotic used to fight infections with multi-resistant bacteria, including Pseudomonas aeruginosa. However, P. aeruginosa can develop resistance to colistin.
In previous studies, the researcher has identified and developed inhibitors of resistance to colistin, capable of restoring the activity of the antibiotic. In this context, the project aimed to produce new molecules with improved pharmacological and biological activity, and to identify “nano-vehicles” for their transport into the CF lung.
In silico analysis were performed to produce drug-like synthetic molecules that reduce colistin resistance, by inhibiting the bacterial ArnT transferase (ArnT-Pa).
The antimicrobial activity of these compounds was tested using assays on strains of Pseudomonas aeruginosa resistant to colistin and in vitro binding to ArnT-Pa. A group of compounds has been identified, some of natural origin, others derived from semi-synthetic processes, which have proven capable of making strains of P. aeruginosa, both laboratory and clinical isolates, sensitive to colistin again, improving the activity and bioavailability of the antibiotic.
Furthermore, liposomal nanoparticles containing both the compound and colistin have been produced and proven to be active, and their antimicrobial activity and toxicity were analyzed. Finally, inhalable prototypes have been developed.
The identified active compounds that block colistin resistance in P. aeruginosa are ready to move on to preclinical studies.