title: Comparative genomics of isolates of a Pseudomonas aeruginosa epidemic strain associated with chronic lung infections of cystic fibrosis patients.
abstract: Pseudomonas aeruginosa is the main cause of fatal chronic lung infections among individuals suffering from cystic fibrosis (CF). During the past 15 years, particularly aggressive strains transmitted among CF patients have been identified, initially in Europe and more recently in Canada. The aim of this study was to generate high-quality genome sequences for 7 isolates of the Liverpool epidemic strain (LES) from the United Kingdom and Canada representing different virulence characteristics in order to: (1) associate comparative genomics results with virulence factor variability and (2) identify genomic and/or phenotypic divergence between the two geographical locations. We performed phenotypic characterization of pyoverdine, pyocyanin, motility, biofilm formation, and proteolytic activity. We also assessed the degree of virulence using the Dictyostelium discoideum amoeba model. Comparative genomics analysis revealed at least one large deletion (40-50 kb) in 6 out of the 7 isolates compared to the reference genome of LESB58. These deletions correspond to prophages, which are known to increase the competitiveness of LESB58 in chronic lung infection. We also identified 308 non-synonymous polymorphisms, of which 28 were associated with virulence determinants and 52 with regulatory proteins. At the phenotypic level, isolates showed extensive variability in production of pyocyanin, pyoverdine, proteases and biofilm as well as in swimming motility, while being predominantly avirulent in the amoeba model. Isolates from the two continents were phylogenetically and phenotypically undistinguishable. Most regulatory mutations were isolate-specific and 29% of them were predicted to have high functional impact. Therefore, polymorphism in regulatory genes is likely to be an important basis for phenotypic diversity among LES isolates, which in turn might contribute to this strain's adaptability to varying conditions in the CF lung.
authors: Institute for integrative and systems biology (IBIS), University Laval, Quebec City, Quebec, Canada.
authors: Julie
authors: J
authors: Jeukens
authors: Institute for integrative and systems biology (IBIS), University Laval, Quebec City, Quebec, Canada.
authors: Brian
authors: B
authors: Boyle
authors: Institute for integrative and systems biology (IBIS), University Laval, Quebec City, Quebec, Canada.
authors: Irena
authors: I
authors: Kukavica-Ibrulj
authors: Institute for integrative and systems biology (IBIS), University Laval, Quebec City, Quebec, Canada ; Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Quebec City, Quebec, Canada.
authors: Myriam M
authors: MM
authors: Ouellet
authors: Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors: Shawn D
authors: SD
authors: Aaron
authors: Institute for integrative and systems biology (IBIS), University Laval, Quebec City, Quebec, Canada ; Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Quebec City, Quebec, Canada.
authors: Steve J
authors: SJ
authors: Charette
authors: Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.
authors: Joanne L
authors: JL
authors: Fothergill
authors: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
authors: Nicholas P
authors: NP
authors: Tucker
authors: Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.
authors: Craig
authors: C
authors: Winstanley
authors: Institute for integrative and systems biology (IBIS), University Laval, Quebec City, Quebec, Canada.
authors: Roger C
authors: RC
authors: Levesque
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics*; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000150:complications / Q000453:epidemiology / Q000382:microbiology*; D016680:Genome, Bacterial; D023281:Genomics; D009154:Mutation; D018410:Pneumonia, Bacterial / Q000150:complications / Q000453:epidemiology / Q000382:microbiology*; D011110:Polymorphism, Genetic; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity
chemical_list: D001426:Bacterial Proteins