Evolutionary genomics of epidemic and nonepidemic strains of Pseudomonas aeruginosa
Edited by Ralph R. Isberg, Howard Hughes Medical Institute and Tufts University School of Medicine, Boston, MA, and approved November 8, 2013 (received for review April 26, 2013)
Significance
The bacterium Pseudomonas aeruginosa is an opportunistic pathogen of humans and is the leading cause of death in patients with cystic fibrosis (CF). We sequenced the genomes of P. aeruginosa isolated from respiratory tracts of patients with CF to investigate general patterns of adaptation associated with chronic infection. Selection imposed by the CF lung environment has had a major influence on genomic evolution and the genetic characteristics of isolates causing contemporary infection. Many of the genes and pathways implicated in adaptive evolution within the host had obvious roles in the pathogenic lifestyle of this bacteria. Genome sequence data indicated that an epidemic strain, with increased virulence and multidrug resistance, has spread between clinics in the United Kingdom and North America.
Abstract
Pseudomonas aeruginosa is an opportunistic pathogen of humans and is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). Prolonged infection of the respiratory tract can lead to adaptation of the pathogen to the CF lung environment. To examine the general patterns of adaptation associated with chronic infection, we obtained genome sequences from a collection of P. aeruginosa isolated from airways of patients with CF. Our analyses support a nonclonal epidemic population structure, with a background of unique, recombining genotypes, and the rare occurrence of successful epidemic clones. We present unique genome sequence evidence for the intercontinental spread of an epidemic strain shared between CF clinics in the United Kingdom and North America. Analyses of core and accessory genomes identified candidate genes and important functional pathways associated with adaptive evolution. Many genes of interest were involved in biological functions with obvious roles in this pathosystem, such as biofilm formation, antibiotic metabolism, pathogenesis, transport, reduction/oxidation, and secretion. Key factors driving the adaptive evolution of this pathogen within the host appear to be the presence of oxidative stressors and antibiotics. Regions of the accessory genome unique to the epidemic strain were enriched for genes in transporter families that efflux heavy metals and antibiotics. The epidemic strain was significantly more resistant than nonepidemic strains to three different antibiotics. Multiple lines of evidence suggest that selection imposed by the CF lung environment has a major influence on genomic evolution and the genetic characteristics of P. aeruginosa isolates causing contemporary infection.
Data Availability
Data deposition: The draft genome sequences reported in this paper have been deposited in the DNA DataBank of Japan (DDBJ)/European Molecular Biology Laboratory/GenBank database, www.ncbi.nlm.nih.gov (accession nos. AWYJ00000000–AWZG00000000).
Acknowledgments
This work was supported by the Natural Sciences and Engineering Research Council of Canada and the Canadian Institutes for Health Research.
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Data Availability
Data deposition: The draft genome sequences reported in this paper have been deposited in the DNA DataBank of Japan (DDBJ)/European Molecular Biology Laboratory/GenBank database, www.ncbi.nlm.nih.gov (accession nos. AWYJ00000000–AWZG00000000).
Submission history
Published online: December 9, 2013
Published in issue: December 24, 2013
Keywords
Acknowledgments
This work was supported by the Natural Sciences and Engineering Research Council of Canada and the Canadian Institutes for Health Research.
Notes
This article is a PNAS Direct Submission.
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Competing Interests
The authors declare no conflict of interest.
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Evolutionary genomics of epidemic and nonepidemic strains of Pseudomonas aeruginosa, Proc. Natl. Acad. Sci. U.S.A.
110 (52) 21065-21070,
https://doi.org/10.1073/pnas.1307862110
(2013).
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