FFC#10/2020

Targeting small RNA-mediated regulation of virulence and antibiotic resistance to develop non-traditional therapeutic options against Pseudomonas aeruginosa

FFC#10/2020

Targeting small RNA-mediated regulation of virulence and antibiotic resistance to develop non-traditional therapeutic options against Pseudomonas aeruginosa

PRINCIPAL INVESTIGATOR

Giovanni Bertoni (Università degli Studi di Milano, Dip. di Bioscienze)

RESEARCHERS

3

CATEGORY

AREA 3 Bronchopulmonary infection

DURATION

1 year

GOAL

€ 37.000 €

RESULTS

This pilot project was part of the emerging trend of research of alternative antimicrobial strategies, such as antivirulence or resensitization to antibiotics currently in use, which can counteract the increase in resistance and the difficulty of developing new antibiotics. The virulence and processes that lead to antibiotic resistance of bacteria can be regulated by small fragments of RNA (sRNA) produced by the bacteria themselves. From previous studies funded by the FFC#13/2015 and FFC#14/2016 projects, the researchers found that the inactivation by mutation of a Pseudomonas aeruginosa (Pa) sRNA called ErsA leads to less biofilm production, which is important for the progression of the infection, a reduction in virulence in the mouse, and if the inactivating ErsA mutation is generated in clinical multidrug-resistant Pa strains, these regain sensitivity to the main antibiotics. During this project, the researchers also found that the inactivation of ErsA in multidrug-resistant Pa strains confers a disadvantage in oxygen-deficient bacterial growth such as that occurs in the context of biofilm. The main goal achieved in this project was to develop and begin testing eight anti-ErsA molecules, called Peptide Nucleic Acids (PNA), potentially capable of blocking the regulatory function of ErsA. In particular, two of these PNAs proved capable of interfering with the regulatory action of ErsA on a target gene taken as a model. In perspective, these PNAs could become new antivirulence drugs capable of re-sensitizing to antibiotics strains of Pa that cannot be eradicated with current antibiotics.

OTHER RESULTS

FFC#2/2022

Characterization of CFTR modulators mechanism of action via Photo-Affinity Labeling (PAL) approach

FFC#6/2022

Search for drug combinations killing Mycobacterium abscessus in cystic fibrosis

FFC#1/2021

Multiomics exploration of the CF primary bronchial epithelium lipidome and its role on CFTR rescue