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New Pseudomonas infections drive Pf phage transmission in CF airways
Julie D. Pourtois, Naomi L. Haddock, Aditi Gupta, Arya Khosravi, Hunter A. Martinez, Amelia K. Schmidt, Prema S. Prakash, Ronit Jain, Piper Fleming, Tony H. Chang, Carlos Milla, Patrick R. Secor, Giulio A. De Leo, Paul L. Bollyky, Elizabeth B. Burgener
Julie D. Pourtois, Naomi L. Haddock, Aditi Gupta, Arya Khosravi, Hunter A. Martinez, Amelia K. Schmidt, Prema S. Prakash, Ronit Jain, Piper Fleming, Tony H. Chang, Carlos Milla, Patrick R. Secor, Giulio A. De Leo, Paul L. Bollyky, Elizabeth B. Burgener
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Research Article Infectious disease Microbiology

New Pseudomonas infections drive Pf phage transmission in CF airways

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Abstract

Pf bacteriophages, lysogenic viruses that infect Pseudomonas aeruginosa (Pa), are implicated in the pathogenesis of chronic Pa infections; phage-infected (Pf+) strains are known to predominate in people with cystic fibrosis (pwCF) who are older and have more severe disease. However, the transmission patterns of Pf underlying the progressive dominance of Pf+ strains are unclear. In particular, it is unknown whether phage transmission commonly occurs horizontally between bacteria via viral particles within the airway or whether Pf+ bacteria are mostly acquired via de novo Pseudomonas infections. Here, we studied Pa genomic sequences from 3 patient cohorts totaling 662 clinical isolates from 105 pwCF. We identified Pf+ isolates and analyzed transmission patterns of Pf within patients between genetically similar groups of bacteria called “clone types.” We found that Pf was predominantly passed down vertically within Pa clone types and rarely via horizontal transfer between clone types within the airway. Conversely, we found extensive evidence of Pa de novo infection by a new, genetically distinct Pf+ Pa. Finally, we observed that clinical isolates showed reduced activity of type IV pili and reduced susceptibility to Pf in vitro. These results cast light on the transmission of virulence-associated phages in the clinical setting.

Authors

Julie D. Pourtois, Naomi L. Haddock, Aditi Gupta, Arya Khosravi, Hunter A. Martinez, Amelia K. Schmidt, Prema S. Prakash, Ronit Jain, Piper Fleming, Tony H. Chang, Carlos Milla, Patrick R. Secor, Giulio A. De Leo, Paul L. Bollyky, Elizabeth B. Burgener

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Figure 4

The majority of changes in the number of Pf phages in patients are associated with colonization or dominance of new clone types.

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The majority of changes in the number of Pf phages in patients are assoc...
(A) Number of changes in the number of Pf phages per patient. (B) Percentage of the changes in the number of Pf phages that are due to a change in clone type or to infection of a clone type by Pf (horizontal transmission). (C) Time series of the number of phages and clone types for patients with at least one change in the number of phages in a clone type over time for the California cohort and for the Denmark cohort. No Pf change occurred within a clone type for any patient of the Italian cohort. Different shapes represent different clone types, while color indicates the number of Pf prophages found in that isolate.

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