Infections and Cystic Fibrosis
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.
At present our research focuses on:
- the analysis of how the immunopathological response targets Pseudomonas aeruginosa and Staphylococcus aureus;
- the definition of genetic mechanisms involved in the pathogenesis of chronic airways infection to better understand individual risk determinants in Cystic Fibrosis;
- the generation of novel mouse models of Cystic Fibrosis by exploring genetically-diverse murine populations that will provide unique tools for disease modeling and pre-clinical studies.
In partnership with the Italian Cystic Fibrosis Research Foundation, we founded a CF animal Core Facility (CFaCore) as a platform for pre-clinical studies and for testing novel antibacterial or anti-inflammatory therapies.
We are making a significant contribution to the advancement of knowledge on the pathogenesis of Cystic Fibrosis, in addition to improving translational studies in the field of pulmonary infections.
Cigana C, Bianconi I, Baldan R, De Simone M, Riva C, Sipione B, Rossi G, Cirillo DM, Bragonzi A. Staphylococcus aureus impacts Pseudomonas aeruginosa chronic respiratory disease in murine models. J Infect Dis. 2018 Mar 5;217(6):933-942.
Spagnuolo L, De Simone M, Lorè NI, De Fino I, Basso V, Mondino A, Cigana C, Bragonzi A. The host genetic background defines diverse immune-reactivity and susceptibility to chronic Pseudomonas aeruginosa respiratory infection. Sci Rep. 2016 Nov 16;6:36924.
Cigana C, Bernardini F, Facchini M, Alcalá-Franco B, Riva C, De Fino I, Rossi A, Ranucci S, Misson P, Chevalier E, Brodmann M, Schmitt M, Wach A, Dale GE, Obrecht D, Bragonzi A. Efficacy of the novel antibiotic POL7001 in preclinical models of Pseudomonas aeruginosa pneumonia. Antimicrob Agents Chemother. 2016 Jul 22;60(8):4991-5000.
Lorè NI, Cigana C, Riva C, De Fino I, Nonis A, Spagnuolo L, Sipione B, Cariani L, Girelli D, Rossi G, Basso V, Colombo C, Mondino A, Bragonzi A. IL-17A impairs host tolerance during airway chronic infection by Pseudomonas aeruginosa. Sci Rep. 2016; 6: 25937.
Cigana C, Lorè NI, Riva C, De Fino I, Spagnuolo L, Sipione B, Rossi G, Nonis A, Cabrini G, Bragonzi A. Tracking the immunopathological response to Pseudomonas aeruginosa during respiratory infections. Sci Rep. 2016 Feb 17;6:21465.
Schughart K, Libert C; SYSGENET consortium, Kas MJ. Controlling complexity: the clinical relevance of mouse complex genetics. Eur J Hum Genet. 2013 Nov;21(11):1191-6.
Imperi F, Massai F, Facchini M, Frangipani E, Visaggio D, Leoni L, Bragonzi A, Visca P. Repurposing the antimycotic drug flucytosine for suppression of Pseudomonas aeruginosa pathogenicity. Proc Natl Acad Sci USA. 2013 Apr 30;110(18):7458-63.
Bianconi I, Milani A, Cigana C, Paroni M, Levesque RC, Bertoni G, Bragonzi A. Positive signature-tagged mutagenesis in Pseudomonas aeruginosa: tracking patho-adaptive mutations promoting airways chronic infection. PLoS Pathog. 2011 Feb 3;7(2):e1001270.
Bragonzi A. Murine models of acute and chronic lung infection with cystic fibrosis pathogens. Int J Med Microbiol. 2010 Dec;300(8):584-93.
Bragonzi A, Paroni M, Nonis A, Cramer N, Montanari S, Rejman J, Di Serio C, Döring G, Tümmler B. Pseudomonas aeruginosa microevolution during cystic fibrosis lung infection establishes clones with adapted virulence. Am J Respir Crit Care Med. 2009 Jul 15;180(2):138-45.