Role of bacteria and the microbial transcriptome during airway infections in people with Cystic fibrosis

Background:Cystic fibrosis (CF) is characterized by frequent airway infections, leading to progressive lung function decline and shortened life-expectancy.

Most CF patients become chronically infected with different bacteria in the lower airways, and once the chronic colonization is established, it often continues for many years or even life-long.

This application focuses on virulence factors of the emerging CF pathogen Achromobacter xylosoxidans, how A. xylosoxidans interacts with other CF pathogens, and bacterial gene expression in vivo during different stages of infection and in response to treatment.

Aim:To characterize virulence factors and host immune responses of A. xylosoxidans.To describe how A. xylosoxidans affects growth and biofilm production of other CF pathogens during co-infections.To monitor in vivo bacterial gene expression of specific bacterial species (transcriptome) or all bacterial species (metatranscriptome) in CF sputum during acute and chronic airway infection, and in response to treatment.

Methods:The application includes clinical translational and pre-clinical studies where we use unique collections of sputum samples from CF patients, clinical A. xylosoxidans isolates collected from chronically infected CF patients over many years, and isogenic bacterial mutants generated in the lab.

The laboratory methods used include bacterial mutagenesis, mass spectrometry, transcriptomics, RT-PCR, et c.