PLoS One. 2014 Feb 5;9(2):e87611. doi: 10.1371/journal.pone.0087611.

Comparative genomics of isolates of a Pseudomonas aeruginosa epidemic strain associated with chronic lung infections of cystic fibrosis patients.

Jeukens J, et al.

Institute for integrative and systems biology (IBIS), University Laval, Quebec City, Quebec, Canada.

 

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.

PMID: 24505294

 

SUPPLEMENT:

Most Cystic Fibrosis patients suffer from and eventually die of chronic lung infection. Our work focusses on Pseudomonas aeruginosa, the main bacteria behind these fatal infections. About 20 years ago, a particularly aggressive strain that could transmit itself among patients was identified, initially in the United Kingdom and more recently in Canada. Isolates of this strain, called the Liverpool epidemic strain, are very diverse in terms of what we call virulence characteristics, the production of toxins for instance. We sequenced the genomes of 7 isolates to understand the genetic basis for this virulence diversity and to determine if Canadian isolates are different from UK isolates. This is the first detailed comparison of transmissible isolates of the same strain from two different continents. First, it was clear that isolates from both continents were very closely related and impossible to differentiate. Second, we found relatively few mutations among the 7 genomes, but many of them were located in genes that influence the expression of other genes. This complex pattern of genetic diversity could help isolates of this strain adapt to changing conditions in the Cystic Fibrosis lung.

 

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