The increase in antibiotic resistance and the delay in discovering new antibacterials stimulate the search for alternative or resensitising strategies for resistant bacteria.
Bacterial small RNAs (sRNAs) represent an unexploited category of therapeutic targets: the ErsA sRNA of Pseudomonas aeruginosa, an important pulmonary pathogen of cystic fibrosis, has been shown to be involved in the regulation of several functions related to lung pathogenesis and antibiotic resistance. The absence of this small RNA causes the bacterium to fail to form a mature biofilm, to be significantly less virulent and to become sensitive to several antibiotics, such as ceftazidime, cefepime and meropenem.
This project originates from FFC#13/2015, FFC#14/2016, FFC#10/2020 e FFC 14/2021, during which anti-ErsA molecules, called PNAs (Peptide Nucleic Acids), were developed. PNA can bind to ErsA and prevent its regulatory function, resensitising a clinical multi-resistant strain  of P. aeruginosa to meropenem.
This project aims to optimize the most effective anti-ErsA PNAs developed to date and test them in a preclinical mouse model of infection to verify their ability to resensitise a multiresistant P. aeruginosa strain to meropenem. Analysis will be conducted in collaboration with the FFC Ricerca CFaCore.
Overall, the aim is to provide innovative molecules for use as anti-Pseudomonas drugs in monotherapy or in combination with antibiotic therapies currently used in cystic fibrosis.