Role of bacteria and the microbial transcriptome during airway infections in patients with Cystic fibrosis and lung transplant recipients

Projekt: Forskning



Cystic fibrosis is characterized by frequent airway infections and inflammation, leading to progressive lung function decline and often the need for lung transplantation. Most CF patients become chronically infected with different bacteria in the lower airways. This application has two over-all aims: 1) to characterise the emerging CF pathogen Achromobacter xylosoxidans, where very little is known about virulence factors involved in the establishment of infection or the inflammatory response by the host, and 2) to monitor the global bacterial gene expression (metatranscriptomics) in airway samples of CF patients and lung transplant recipients, and to correlate transcriptome profiles to infection and lung function decline.

I. To develop genetic methods and models to establish the role of specific protein secretion systems for the virulence and immune modulation by A. xylosoxidans.
II. To characterise pro-inflammatory properties and host-pathogen interactions in different Achromobacter species.
III. To monitor the in vivo bacterial gene expression of A. xylosoxidans and P. aeruginosa in CF sputum samples during acute and chronic airway infection and in response to antibiotic treatment.
IV. To monitor global bacterial gene expression, including virulence determinants, in bronchoalveolar lavage fluids from lung transplant recipients, and to correlate metatranscriptome profiles to clinical signs of infection and lung function decline.

The application includes clinical translational and pre-clinical studies where we use clinical isolates and isogenic mutants of Achromobacter, and unique collections of sputum samples from CF patients and bronchoalveolar lavage samples from lung transplant recipients. The laboratory methods used include bacterial mutagenesis, cell infection models, proteomics, RNA sequencing, and transcriptomics.

The results will increase our knowledge of the molecular pathogenesis of the hitherto under-explored A. xylosoxidans and related Achromobacter species. More specifically, the projects could identify new therapeutic targets for infections caused by A. xylosoxidans, and the development of new antimicrobials in the longer perspective. The project can also increase our understanding of the complex interplay between different bacterial species in the airways, and how the inter-species dynamics can cause infection and lung function decline.
Gällande start-/slutdatum2022/12/012025/12/31


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