The Microbiome of Cystic Fibrosis Sputum and its Association with Incident Lower Airway Infections
Date
2024-09
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Abstract
Cystic fibrosis (CF) is a genetic disease characterised by frequent respiratory infections that exacerbate symptoms, leading to a decline in lung function and increased morbidity and mortality. Pseudomonas aeruginosa is considered the primary pathogen in CF, contributing significantly to disease severity. Stenotrophomonas maltophilia is an emerging pathogen of interest, associated with increased pulmonary exacerbations and lung function decline. This thesis aimed to explore the CF sputum microbiome of persons with CF (pwCF) uninfected with these pathogens and to determine if the risk of future acquisition and persistence of these pathogens is linked to microbiome structure and composition. Individuals who experienced an incident infection with either P. aeruginosa or S. maltophilia were identified, and compared to uninfected controls matched for sex, age (+/-2 years), and birth cohort. Individuals were included if our longitudinal whole sputum biobank contained cryopreserved samples from one year prior to infection (pre), at the time of culture-based identification of infection (at), and one year following infection (post). Infection outcomes were classified as chronic/persistent (pathogen culture-positive in ≥50% of cultures in the subsequent year) or transient. The microbial community composition was assessed using V3-V4 16S ribosomal RNA (rRNA) gene sequencing. Relative abundance data were verified using both pathogen-specific qPCR and total 16S rRNA-targeted qPCR to assess bacterial bioburden. Strains were typed using pulse-field gel electrophoresis to differentiate strain types and distinguish incident infection episodes. Results from this work showed that the microbial community of pwCF that eventually developed P. aeruginosa, or S. maltophilia incident infections differed from those who remained uninfected at the times of sampling. Additionally, at the time of infection, the microbial community composition differed between individuals with persistent infections and those whose infections were cleared. These findings suggest that the sputum microbiome in pwCF is associated with future infection risk and persistence, indicating its potential as a biomarker for prognosis and personalised treatment.
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Keywords
microbiome, cystic fibrosis, bronchiectasis, incident infections, pseudomonas aeruginosa, stenotrophomonas maltophilia
Citation
Bowron, L. A. (2024). The microbiome of cystic fibrosis sputum and its association with incident lower airway infections (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.