FFC#13/2016

Establishment of single‐cell and animal model to investigate pathogenesis of infection by Mycobacterium abscessus complex members in cystic fibrosis patients

FFC#13/2016

Establishment of single‐cell and animal model to investigate pathogenesis of infection by Mycobacterium abscessus complex members in cystic fibrosis patients

PRINCIPAL INVESTIGATOR

Enrico Tortoli (Unità Batteri Patogeni Emergenti, Divisione di Immunologia, Trapianti e Malattie Infettive, Istituto Scientifico San Raffaele, Milano)

Partner

Carla Colombo (Centro Lombardo FC. Fondazione IRCSS Ca’ Granda, Ospedale Maggiore Policlinico, Milano); Maria Clelia Di Serio (CVSSB, Università Vita-Salute San Raffaele, Milano)

RESEARCHERS

12

CATEGORY

AREA 3 Bronchopulmonary infection

DURATION

1 year

GOAL

€ 50.000 €

RESULTS

In this study researchers studied chronic infection by Mycobacterium Abscessus in C57Bl/6NCr mice: mice were monitored for body weight, mortality and lungs were processed for microbiological analysis, inflammatory response and histological evaluation.
The results demonstrated that Mycobacterium Abscessus modified agar beads preparation from the standard protocol was able to establish a chronic infection in mice C57Bl/6NCr up to 75 days with MA sspp abscessus, bolleti and massiliense, with a low rate of clearance. The analysis of the bacterial load in the total lung showed a high and stable number of colony forming unit during the course of infection with minimal systemic spread and stable inflammatory response in broncoalveolar lavage fluid (BALF) up to 75 days of infection. Lung histopathological analysis revealed granulomatomatous response with lymphocytes and macrophage aggregation that are disseminated in the lung during the course of MA infection. Through extension project FFC#20/2017, six MA strains, belonging to the three sspp and isolated both from chronic symptomatic and asymptomatic CF patients, will be tested in murine model of chronic lung infection. The availability of a murine model for MA chronic infection will allow the identification of strains causing severe pulmonary disease and to evaluate in vivo novel antimycobacterial protocols.

OTHER RESULTS

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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