FFC#11/2020

Disrupting Pseudomonas aeruginosa Quorum Sensing signalling in Cystic Fibrosis patients as a new frontier for antibacterial therapy

FFC#11/2020

Disrupting Pseudomonas aeruginosa Quorum Sensing signalling in Cystic Fibrosis patients as a new frontier for antibacterial therapy

PRINCIPAL INVESTIGATOR

Paola Brun (Università degli Studi di Padova, Dip. di Medicina Molecolare)

Partner

Giovanni Marzaro (Università degli Studi di Padova, Dip. di Scienze Farmaceutiche e Farmacologiche)

RESEARCHERS

10

CATEGORY

AREA 3 Bronchopulmonary infection

DURATION

1 year

GOAL

€ 50.000 €

RESULTS

Through a preliminary in vitro screening of a library of 100 molecules, the researchers identified the main structural characteristics needed for the inhibition of the quorum sensing that represents the “language” made of chemical signals used by bacterial species, such as Pseudomonas aeruginosa (Pa), to communicate with each other. The researchers then interrogated FDA libraries of drugs already approved for other therapeutic approaches and identified two compounds, Azaperone and MK-8245, as the most active in reducing virulence factors in P. aeruginosa. Indeed, the two compounds damped the ability of the bacterium in invading the host and in producing biofilm. Interestingly, the compounds also counteracted Pa infection in Gallera mellonella, an insect used as an experimental model to test antimicrobial compounds. The researchers confirmed the antivirulence effects of the compounds in 23 clinical isolates of P. aeruginosa obtained from patients with cystic fibrosis. The obtained results validated the use of already approved drugs as quorum sensing inhibitors active in Pa and provided insights into ready-to-use treatments for lung infections in cystic Fibrosis.

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