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.
Rothia mucilaginosa is an anti-inflammatory bacterium in the respiratory tract of patients with chronic lung disease. Rigauts C, Aizawa J, Taylor S, Rogers GB, Govaerts M, Cos P, Ostyn L, Sims S, Vandeplassche E, Sze M, Dondelinger Y, Vereecke L, Van Acker H, Simpson JL, Burr L, Willems A, Tunney MM, Cigana C, Bragonzi A, Coenye T, Crabbé A. Eur Respir J. 2021 Sep 29:2101293. doi: 10.1183/13993003.01293-2021.
Pharmacological modulation of mitochondrial calcium uniporter controls lung inflammation in cystic fibrosis. Rimessi A, Pozzato C, Carparelli L, Rossi A, Ranucci S, De Fino I, Cigana C, Talarico A, Wieckowski MR, Ribeiro CMP, Trapella C, Rossi G, Cabrini G, Bragonzi A, Pinton P. Sci Adv. 2020 May 6;6(19):eaax9093.
Collaborative Cross Mice Yield Genetic Modifiers for Pseudomonas aeruginosa Infection in Human Lung Disease. Lorè NI, Sipione B, He G, Strug LJ, Atamni HJ, Dorman A, Mott R, Iraqi FA, Bragonzi A. mBio. 2020 Mar 3;11(2):e00097-20.
Antibiotic efficacy varies based on the infection model and treatment regimen for Pseudomonas aeruginosa. Cigana C, Ranucci S, Rossi A, De Fino I, Melessike M, Bragonzi A. Eur Respir J. 2020 Mar 5;55(3):1802456.
Genome-Based Approach Delivers Vaccine Candidates Against Pseudomonas aeruginosa. Bianconi I, Alcalá-Franco B, Scarselli M, Dalsass M, Buccato S, Colaprico A, Marchi S, Masignani V, Bragonzi A. Front Immunol. 2019 Jan 9;9:3021.
Staphylococcus aureus Impacts Pseudomonas aeruginosa Chronic Respiratory Disease in Murine Models. Cigana C, Bianconi I, Baldan R, De Simone M, Riva C, Sipione B, Rossi G, Cirillo DM, Bragonzi A. J Infect Dis. 2018 Mar 5;217(6):933-942.
Inflammation and host-pathogen interaction: Cause and consequence in cystic fibrosis lung disease. Bragonzi A, Horati H, Kerrigan L, Lorè NI, Scholte BJ, Weldon S. J Cyst Fibros. 2018 Mar;17(2S):S40-S45.
Resolvin D1 enhances the resolution of lung inflammation caused by long-term Pseudomonas aeruginosa infection. Codagnone M, Cianci E, Lamolinara A, Mari VC, Nespoli A, Isopi E, Mattoscio D, Arita M, Bragonzi A, Iezzi M, Romano M, Recchiuti A.Mucosal Immunol. 2018 Jan;11(1):35-49.
Lentiviral Vector Gene Therapy Protects XCGD Mice From Acute Staphylococcus aureus Pneumonia and Inflammatory Response. Farinelli G, Jofra Hernandez R, Rossi A, Ranucci S, Sanvito F, Migliavacca M, Brombin C, Pramov A, Di Serio C, Bovolenta C, Gentner B, Bragonzi A, Aiuti A. Mol Ther. 2016 Oct;24(10):1873-1880.
Efficacy of the Novel Antibiotic POL7001 in Preclinical Models of Pseudomonas aeruginosa Pneumonia. 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. Antimicrob Agents Chemother. 2016 Jul 22;60(8):4991-5000.
The IL-17A/IL-17RA axis in pulmonary defence and immunopathology. Lorè NI, Bragonzi A, Cigana C. Cytokine Growth Factor Rev. 2016 Aug;30:19-27.
Repurposing the antimycotic drug flucytosine for suppression of Pseudomonas aeruginosa pathogenicity. Imperi F, Massai F, Facchini M, Frangipani E, Visaggio D, Leoni L, Bragonzi A, Visca P. Proc Natl Acad Sci U S A. 2013 Apr 30;110(18):7458-63.
Positive signature-tagged mutagenesis in Pseudomonas aeruginosa: tracking patho-adaptive mutations promoting airways chronic infection. Bianconi I, Milani A, Cigana C, Paroni M, Levesque RC, Bertoni G, Bragonzi A. PLoS Pathog. 2011 Feb 3;7(2):e1001270.
Murine models of acute and chronic lung infection with cystic fibrosis pathogens. Bragonzi A. Int J Med Microbiol. 2010 Dec;300(8):584-93.
Fighting back: peptidomimetics as a new weapon in the battle against antibiotic resistance. Bragonzi A. Sci Transl Med. 2010 Mar 3;2(21):21ps9.