Bacterial small RNAs (sRNAs) represent a largely unexploited category of potential new targets to design anti-virulence therapy; they have been shown to play key roles also in microbial processes leading to antibiotic resistance. In this background, the main aims of this proposal, that continues FFC#13/2015 project, are: i) to assess the involvement of three newly discovered P. aeruginosa sRNAs (named ErsA, ReaL and SPA0021) in regulatory mechanisms underlying antibiotics resistance; ii) to investigate their capacity to establish chronic infection in murine models, and their impact on antibiotic treatments. Important knowledge for developing next-generation antibiotics that will have sRNAs as novel targets are expected.