Team:
Silvia Ferrara, Eloise Mastrangelo
Collaborations:
Giovanni Bertoni (Università degli Studi di Milano), Alessandra Bragonzi (San Raffaele Scientific Institute)
Pseudomonas aeruginosa is a major multidrug-resistant pathogen responsible for severe acute and chronic infections, particularly in hospitalized and cystic fibrosis patients. Its adaptability relies on complex regulatory networks controlling virulence, biofilm formation, and persistence.
This project focuses on the functional and biophysical characterization of key small regulatory RNAs (sRNAs) in P. aeruginosa, with the aim of mapping their molecular interaction networks. We investigate RNA folding dynamics, RNA–RNA and RNA–protein interactions, and their integration with cellular signaling pathways such as the second messenger c-di-GMP, to define the molecular principles governing sRNA-mediated regulation in pathogenicity circuits. On this basis, we develop next-generation antibacterial strategies based on peptide nucleic acids (PNAs) designed to selectively target regulatory RNAs, disrupt key regulatory interactions, and attenuate virulence, with the ultimate goal of restoring antibiotic susceptibility in multidrug-resistant P. aeruginosa.
Funding:
PNRR PE-13 INF-ACT, FFC#5/2024
