title: Evolutionary genomics of epidemic and nonepidemic strains of Pseudomonas aeruginosa.
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.
authors: Department of Biology, Centre for Advanced Research in Environmental Genomics, and Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada K1N 6N5.
authors: Jeremy R
authors: JR
authors: Dettman
authors: Nicolas
authors: N
authors: Rodrigue
authors: Shawn D
authors: SD
authors: Aaron
authors: Rees
authors: R
authors: Kassen
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics*; D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001483:Base Sequence; D005075:Biological Evolution; D019295:Computational Biology; D003550:Cystic Fibrosis / Q000382:microbiology*; D018432:Drug Resistance, Multiple; D063990:Gene Ontology; D014644:Genetic Variation; D023281:Genomics; D006801:Humans; D016013:Likelihood Functions; D008826:Microbial Sensitivity Tests; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009656:North America; D009864:Ontario; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity*; D017422:Sequence Analysis, DNA; D006113:United Kingdom; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents
keywords: multidrug resistance; redox balance; virulence