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Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Filamentous bacteriophages are associated with chronic Pseudomonas lung infections and antibiotic resistance in cystic fibrosis

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  1. Distinct immune phenotypes in infants developing asthma during childhood

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  2. Imaging-assisted nanoimmunotherapy for atherosclerosis in multiple species

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  3. Enhanced detection of circulating tumor DNA by fragment size analysis

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  4. Evaluation of liquid from the Papanicolaou test and other liquid biopsies for the detection of endometrial and ovarian cancers

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  5. Direct detection of early-stage cancers using circulating tumor DNA

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  1. Primary ciliary dyskinesia patients have the same P. aeruginosa clone in sinuses and lungs

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  2. Variant in ERAP1 promoter region is associated with low expression in a patient with a Behçet-like MHC-I-opathy

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Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftScience translational medicine
Vol/bind11
Udgave nummer488
Sider (fra-til)eaau9748
ISSN1946-6234
DOI
StatusUdgivet - 17 apr. 2019

Bibliografisk note

Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

ID: 59017738