FFC#14/2016

Role of small RNA-based regulatory systems in cystic fibrosis airways infection by Pseudomonas aeruginosa: a new frontier in the identification of molecular targets for novel antibacterials

FFC#14/2016

Role of small RNA-based regulatory systems in cystic fibrosis airways infection by Pseudomonas aeruginosa: a new frontier in the identification of molecular targets for novel antibacterials

PRINCIPAL INVESTIGATOR

Giovanni Bertoni (Dipartimento di Bioscienze, Università degli Studi di Milano)

RESEARCHERS

5

CATEGORY

AREA 3 Bronchopulmonary infection

DURATION

1 year

GOAL

€ 25.000 €

RESULTS

To investigate the role of sRNA in regulatory mechanisms underlying antibiotic resistance, in murine models of chronic infection sRNA-deleted mutants were subjected to minimum Inhibitory Concentrations (MICs) determination of antibiotics commonly used in the clinical practice and tests for virulence. The results confirmed the role of sRNA in conferring virulence to bacteria. The sRNA ErsA was particularly studied and it was shown that ErsA deletion strongly reduces the virulence of P. aeruginosa in a murine model of chronic infection. This result correlates with the observation that an ErsA-deleted mutant is less pro-inflammatory than the wild-type and induces lower cell death in infected bronchial epithelial cells. The achievements of this project have the potential to foster the development of innovative antimicrobial strategies: using sRNA as novel targets, the effort is to identify drug molecules that can bind and inhibit sRNA functions.

OTHER RESULTS

FFC #3/2024

Two molecules are effective in activating Heat Shock Proteins and enhancing the action of CFTR correctors with the F508del mutation in vitro.

FFC#5/2024

Some peptide nucleic acids (PNAs) re-sensitise Pseudomonas aeruginosa to the antibiotic meropenem in vitro and reduce its virulence.

FFC#1/2023

Tezacaftor, one of the components of Kaftrio, induces an accumulation of dihydroceramides both in vitro and in vivo in animal models