Emerging candidates as molecular regulators of infection and virulence in P. aeruginosa are small RNAs (sRNAs), which in other bacterial pathogens have been shown to play key roles in modulating cellular processes linked to pathogenesis. From this perspective, the main aims of this proposal are: i) the evaluation of the impact on P. aeruginosa virulence and infection of a selected panel of new sRNAs; ii) the identification of the virulence/infection functions that are regulated by these sRNAs; iii) the characterization of the sRNA/target interactions. These main goals of the project will be achieved through the accomplishment of five specific aims: 1. test of sRNA mutants for virulence on CF pneumocyte cell lines; 2. challenge of sRNAs mutants in animal models of airways infection; 3. analysis of sRNAs expression in clinical P. aeruginosa strains; 4. proteomics screenings for sRNA targets; 5. validation and characterization of sRNA/target interactions.