Genes required for free phage production are essential for pseudomonas aeruginosa chronic lung infections

Andrée-Ann Lemieux, Julie Jeukens, Irena Kukavica-Ibrulj, Joanne L. Fothergill, Brian Boyle, Jérôme Laroche, Nicholas P. Tucker, Craig Winstanley, Roger C. Levesque

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Abstract

The opportunistic pathogen Pseudomonas aeruginosa causes chronic lung infection in patients with cystic fibrosis. The Liverpool Epidemic Strain LESB58 is highly resistant to antibiotics, transmissible, and associated with increased morbidity and mortality. Its genome contains 6 prophages and 5 genomic islands. We constructed a polymerase chain reaction (PCR)-based signature-tagged mutagenesis library of 9216 LESB58 mutants and screened the mutants in a rat model of chronic lung infection. A total of 162 mutants were identified as defective for in vivo maintenance, with 11 signature-tagged mutagenesis mutants having insertions in prophage and genomic island genes. Many of these mutants showed both diminished virulence and reduced phage production. Transcription profiling by quantitative PCR and RNA-Seq suggested that disruption of these prophages had a widespread trans-acting effect on the transcriptome. This study demonstrates that temperate phages play a pivotal role in the establishment of infection through modulation of bacterial host gene expression.

Original languageEnglish
Pages (from-to)395-402
Number of pages8
JournalJournal of Infectious Diseases
Volume213
Issue number3
Early online date12 Aug 2015
DOIs
Publication statusPublished - 1 Feb 2016

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Keywords

  • pseudomonas aeruginosa
  • bacteriophages
  • virulence
  • chronic infection
  • respiratory health
  • gene expression

Cite this

Lemieux, A-A., Jeukens, J., Kukavica-Ibrulj, I., Fothergill, J. L., Boyle, B., Laroche, J., ... Levesque, R. C. (2016). Genes required for free phage production are essential for pseudomonas aeruginosa chronic lung infections. Journal of Infectious Diseases, 213(3), 395-402. https://doi.org/10.1093/infdis/jiv415