FFC#5/2022

Nontuberculous mycobacteria in cystic fibrosis: scouting molecules against M. abscessus iron acquisition pathways

AREA 3 Bronchopulmonary infection

FFC#5/2022

Nontuberculous mycobacteria in cystic fibrosis: scouting molecules against M. abscessus iron acquisition pathways
€ 0 still needed
0%
€ 130.000 goal

pRINCIPAL INVESTIGATOR

Laurent Robert Chiarelli (Laboratorio di Microbiologia molecolare, Dip. Biologia e Biotecnologia “Lazzaro Spallanzani”, Università di Pavia)

Partner

Fiorella Meneghetti (Dip. di Scienze Farmaceutiche, Università degli Studi di Milano), Sonia Covaceuszach (Istituto di Cristallografia, CNR, Basovizza, Trieste)

Researchers

10

Category

AREA 3 Bronchopulmonary infection

Duration

2 anni

Goal

€ 130.000

Funds raised

€ 130.000

Objectives

This project aims to identify alternative strategies to manage the infections caused by non-tuberculous mycobacteria (NTM) that are increasing among people with cystic fibrosis (CF). Mycobacterium abscessus (Mab) among the NTMs is the one that is spreading the most and of greatest concern, as it is resistant to many drugs and able to develop resistance to antibiotics very easily. For this reason, drug treatment is very long and not always effective and its negative outcome leads to a rapid decline in lung functions. It is therefore of primary importance to identify new therapeutic targets and new drugs against Mabs. With this project the research team wants to develop anti-virulence molecules, which block the infection but do not induce resistance in bacteria. Among the anti-virulence compounds for Mabs, there are those that interfere with iron metabolism, which appear to be promising since this metal is essential for the infection phase. Mabs capture iron in the environment thanks to molecules called siderophores and their inhibition can be strategic for carrying out this anti-virulence activity. The research group has developed compounds capable of inhibiting the Salicylate Synthase (SaS) of Mycobacterium tuberculosis, an enzyme essential for the synthesis of siderophores. Based on the results obtained, and considering the similarities between the different mycobacteria (such as M. abscessus and M. tuberculosis), the researchers intend to develop molecules that inhibit SaS. The effectiveness of different compounds will be tested on a SaS enzyme specially produced and used as an experimental model. For those who show inhibition of the enzyme, the interaction between compound and SaS will be studied in order to obtain useful structural information for the optimization of the compounds. The most promising compounds will be subjected to a series of biochemical, biophysical, microbiological and toxicological analyzes to then aim at obtaining new potential drugs.

CHI HA ADOTTATO IL PROGETTO

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€ 8.000

Gruppo di sostegno FFC Ricerca di Grado – Gorizia

€ 10.000

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€ 8.000

Delegazione FFC Ricerca di Monterotondo Roma

€ 8.000

Delegazione FFC Ricerca di Trieste

€ 10.000

Delegazione FFC Ricerca di Sassari Castelsardo

€ 58.000

Delegazione FFC Ricerca di Vigevano

€ 8.000

Delegazione FFC Ricerca di Moncalvo

€ 12.000

Delegazione FFC Ricerca di Lecce

€ 8.000

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