This project is part of the emerging trend of research on alternative antimicrobial strategies aimed at countering the ever-increasing resistance to antibiotics and counterbalancing the difficulty of developing new antibiotics. For example, those working in this sector aim to develop so-called anti-virulence drugs, capable of counteracting the functions that make a bacterium aggressive, or molecules capable of re-sensitizing a bacterium that has become resistant to antibiotics. Bacterial virulence and antibiotic resistance can be regulated by small fragments of RNA (sRNA) produced by the bacteria themselves. From previous studies funded by the Foundation, the researchers discovered that the mutation of a Pseudomonas aeruginosa (Pa) sRNA called ErsA leads to less biofilm production, important for the progression of infection, and a reduction in virulence in mice. If the ErsA mutation is generated in multidrug-resistant clinical strains of Pa, these regain sensitivity to the main antibiotics and are disadvantaged in biofilm growth in the absence of oxygen. Therefore, the use of ErsA as an anti-Pa target aims to re-sensitize multi-resistant strains to antibiotics and to counteract their biofilm growth. The main goal achieved in this project was to develop, validate and test eight anti-ErsA molecules, called Peptide Nucleic Acids (PNA). In particular, two of these PNAs have been shown to interfere with the regulatory action of ErsA on a target gene taken as a model. Furthermore, the researchers achieved the important result of being able to re-sensitize multidrug-resistant strains to a class of antibiotics by administering PNA to the bacteria. The next step will be to assess whether PNAs are also capable of counteracting biofilm formation. Looking ahead, these PNAs could become new anti-Pa drugs to be administered in case of infection with Pa strains that cannot be eradicated with current antibiotics.