Genes Required for Free Phage Production are Essential for Pseudomonas aeruginosa Chronic Lung Infections.
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.
Institut de biologie intégrative et des systèmes, Université Laval, Québec City, Canada.
Andrée-Ann
AA
Lemieux
Institut de biologie intégrative et des systèmes, Université Laval, Québec City, Canada.
Julie
J
Jeukens
Institut de biologie intégrative et des systèmes, Université Laval, Québec City, Canada.
Irena
I
Kukavica-Ibrulj
Institute of Infection and Global Health, University of Liverpool.
Joanne L
JL
Fothergill
Institut de biologie intégrative et des systèmes, Université Laval, Québec City, Canada.
Brian
B
Boyle
Institut de biologie intégrative et des systèmes, Université Laval, Québec City, Canada.
Jérôme
J
Laroche
Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
Nicholas P
NP
Tucker
Institute of Infection and Global Health, University of Liverpool.
Craig
C
Winstanley
Institut de biologie intégrative et des systèmes, Université Laval, Québec City, Canada.
Roger C
RC
Levesque
D000818:Animals; D002908:Chronic Disease; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D005798:Genes, Bacterial; D044404:Genomic Islands; D008171:Lung Diseases / Q000382:microbiology*; D009154:Mutation; D039002:Prophages / Q000235:genetics / Q000378:metabolism; D011552:Pseudomonas Infections / Q000382:microbiology*; D017105:Pseudomonas Phages / Q000502:physiology*; D051381:Rats; D059467:Transcriptome; D014779:Virus Replication / Q000502:physiology*
Pseudomonas aeruginosa; bacteriophages; chronic infection; gene expression; respiratory health; virulence