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The Capital Region of Denmark - a part of Copenhagen University Hospital
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Filamentous bacteriophages are associated with chronic Pseudomonas lung infections and antibiotic resistance in cystic fibrosis

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  1. Delivery mode and gut microbial changes correlate with an increased risk of childhood asthma

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  2. Epigenetic markers associated with metformin response and intolerance in drug-naive patients with type 2 diabetes

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  3. Distinct immune phenotypes in infants developing asthma during childhood

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  4. A dual-action peptide-containing hydrogel targets wound infection and inflammation

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  5. Imaging-assisted nanoimmunotherapy for atherosclerosis in multiple species

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  1. Update 2016-2018 of the Nationwide Danish Fungaemia Surveillance Study: Epidemiologic Changes in a 15-Year Perspective

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  2. Omics-based tracking of Pseudomonas aeruginosa persistence in "eradicated" cystic fibrosis patients.

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Filamentous bacteriophage (Pf phage) contribute to the virulence of Pseudomonas aeruginosa infections in animal models, but their relevance to human disease is unclear. We sought to interrogate the prevalence and clinical relevance of Pf phage in patients with cystic fibrosis (CF) using sputum samples from two well-characterized patient cohorts. Bacterial genomic analysis in a Danish longitudinal cohort of 34 patients with CF revealed that 26.5% (n = 9) were consistently Pf phage positive. In the second cohort, a prospective cross-sectional cohort of 58 patients with CF at Stanford, sputum qPCR analysis showed that 36.2% (n = 21) of patients were Pf phage positive. In both cohorts, patients positive for Pf phage were older, and in the Stanford CF cohort, patients positive for Pf phage were more likely to have chronic P. aeruginosa infection and had greater declines in pulmonary function during exacerbations than patients negative for Pf phage presence in the sputum. Last, P. aeruginosa strains carrying Pf phage exhibited increased resistance to antipseudomonal antibiotics. Mechanistically, in vitro analysis showed that Pf phage sequesters these same antibiotics, suggesting that this mechanism may thereby contribute to the selection of antibiotic resistance over time. These data provide evidence that Pf phage may contribute to clinical outcomes in P. aeruginosa infection in CF.

Original languageEnglish
JournalScience translational medicine
Volume11
Issue number488
Pages (from-to)eaau9748
ISSN1946-6234
DOIs
Publication statusPublished - 17 Apr 2019

ID: 59017738