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Rigshospitalet - a part of Copenhagen University Hospital
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Pre-adapting parasitic phages to a pathogen leads to increased pathogen clearance and lowered resistance evolution with Pseudomonas aeruginosa cystic fibrosis bacterial isolates

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DOI

  1. Ascertainment biases in SNP chips affect measures of population divergence

    Research output: Contribution to journalJournal articleResearchpeer-review

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

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Structure of Pseudomonas aeruginosa ribosomes from an aminoglycoside-resistant clinical isolate

    Research output: Contribution to journalJournal articleResearchpeer-review

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

    Research output: Contribution to journalJournal articleResearchpeer-review

  • V-P Friman
  • D Soanes-Brown
  • P Sierocinski
  • S Molin
  • H K Johansen
  • M Merabishvili
  • J-P Pirnay
  • D De Vos
  • A Buckling
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Recent years have seen renewed interest in phage therapy--the use of viruses to specifically kill disease-causing bacteria--because of the alarming rise in antibiotic resistance. However, a major limitation of phage therapy is the ease at with bacteria can evolve resistance to phages. Here, we determined whether in vitro experimental coevolution can increase the efficiency of phage therapy by limiting the resistance evolution of intermittent and chronic cystic fibrosis Pseudomonas aeruginosa lung isolates to four different phages. We first pre-adapted all phage strains against all bacterial strains and then compared the efficacy of pre-adapted and nonadapted phages against ancestral bacterial strains. We found that evolved phages were more efficient in reducing bacterial densities than ancestral phages. This was primarily because only 50% of bacterial strains were able to evolve resistance to evolved phages, whereas all bacteria were able to evolve some level of resistance to ancestral phages. Although the rate of resistance evolution did not differ between intermittent and chronic isolates, it incurred a relatively higher growth cost for chronic isolates when measured in the absence of phages. This is likely to explain why evolved phages were more effective in reducing the densities of chronic isolates. Our data show that pathogen genotypes respond differently to phage pre-adaptation, and as a result, phage therapies might need to be individually adjusted for different patients.

Original languageEnglish
JournalMolecular Biology and Evolution
Volume29
Issue number1
Pages (from-to)188-98
Number of pages11
ISSN0737-4038
DOIs
Publication statusPublished - Jan 2016

    Research areas

  • Adaptation, Biological, Biological Evolution, Cystic Fibrosis, Host-Pathogen Interactions, Humans, Pseudomonas Phages, Pseudomonas aeruginosa, Journal Article, Research Support, Non-U.S. Gov't

ID: 49928424