Immunology, Transplantation and Infectious diseases

Infections and Cystic Fibrosis

team-item

Group leader

Alessandra Bragonzi

MORE

Persistent bacterial infections pose serious health problems for humans, including Cystic Fibrosis patients. After an initial acute disease state, that is kept in check by host immune response, bacteria as Pseudomonas aeruginosa and Staphylococcus aureus can establish persistent infections and colonize the host by evading immune surveillance. Our scientific research program aims to elucidate genetic and molecular mechanisms involved in the host-pathogen interactions during initial and persistent infection. Our objective is to devise new therapeutic approaches for the treatment of respiratory infections. We have combined microbiology and immunology with functional genetics and have developed critical mouse models of chronic bacterial infection that reproduce the advanced-stage human pulmonary pathology.

Research activity

Determinants of host/pathogen interactions in respiratory diseases.

The group has been focusing on the bacterial molecular mechanisms and immune response governing chronic respiratory infections. Our research explores the genomic features of bacterial pathoadaptive variants found in long-term chronic infections, especially those of multi-drug resistant strains. Among the main organisms we are currently studying is Pseudomonas aeruginosa, which exhibits genomic features of considerable complexity. We employ genomic approaches to provide a genome-scale picture of bacterial evolution and identify novel functions involved in lung pathogenesis for targeted interventions to mitigate lung-damaging infection and inflammation. By using both in vitro and in vivo models, we define novel virulence determinants in adapted bacterial populations and identify new targets for improved antimicrobial therapies.

The research also covers the signalling process of the host immune response, which ultimately affect the course and severity of the respiratory disease. We use various mouse models of acute and chronic infections, including the Collaborative Cross mouse model, to mimic different stages of respiratory disease and reflect the allelic diversity of the human population. Our goal is to dissect the pathogenesis of chronic infection to identify novel biomarkers for use in diagnostics and therapeutic interventions.

Evaluation of novel drugs for treating respiratory infection and inflammation. Our group support pre-clinical research with animal models and drug testing within the Cystic Fibrosis Animal Core Facility (CFaCore). CFaCore provides dedicated scientific and regulatory support to significantly advance preclinical studies in infectious disease and CF research. We develop pre-clinical models of acute and chronic respiratory infections, featuring reference and clinical bacterial strains, as well as transgenic CF mice. We set-up comprehensive read-outs and data analysis, covering both the pathogen and host response, including lung function measurements. Our objective is to support research on pathogenesis and candidate therapeutic molecules, facilitating the translation of basic research projects into pre-clinical applications.

Click here to view our publications