title: Adaptive mutations and replacements of virulence traits in the Escherichia coli O104:H4 outbreak population.
abstract: The sequencing of highly virulent Escherichia coli O104:H4 strains isolated during the outbreak of bloody diarrhea and hemolytic uremic syndrome in Europe in 2011 revealed a genome that contained a Shiga toxin encoding prophage and a plasmid encoding enteroaggregative fimbriae. Here, we present the draft genome sequence of a strain isolated in Sweden from a patient who had travelled to Tunisia in 2010 (E112/10) and was found to differ from the outbreak strains by only 38 SNPs in non-repetitive regions, 16 of which were mapped to the branch to the outbreak strain. We identified putatively adaptive mutations in genes for transporters, outer surface proteins and enzymes involved in the metabolism of carbohydrates. A comparative analysis with other historical strains showed that E112/10 contained Shiga toxin prophage genes of the same genotype as the outbreak strain, while these genes have been replaced by a different genotype in two otherwise very closely related strains isolated in the Republic of Georgia in 2009. We also present the genome sequences of two enteroaggregative E. coli strains affiliated with phylogroup A (C43/90 and C48/93) that contain the agg genes for the AAF/I-type fimbriae characteristic of the outbreak population. Interestingly, C43/90 also contained a tet/mer antibiotic resistance island that was nearly identical in sequence to that of the outbreak strain, while the corresponding island in the Georgian strains was most similar to E. coli strains of other serotypes. We conclude that the pan-genome of the outbreak population is shared with strains of the A phylogroup and that its evolutionary history is littered with gene replacement events, including most recently independent acquisitions of antibiotic resistance genes in the outbreak strains and its nearest neighbors. The results are summarized in a refined evolutionary model for the emergence of the O104:H4 outbreak population.
authors.affiliation: Department of Molecular Evolution, Cell and Molecular Biology, Science for Life Laboratory, Biomedical Centre, Uppsala University, Uppsala, Sweden.
authors.forename: Lionel
authors.initials: L
authors.lastname: Guy
authors.forename: Cecilia
authors.initials: C
authors.lastname: Jernberg
authors.forename: Jenny
authors.initials: J
authors.lastname: Arvén Norling
authors.forename: Sofie
authors.initials: S
authors.lastname: Ivarsson
authors.forename: Ingela
authors.initials: I
authors.lastname: Hedenström
authors.forename: Öjar
authors.initials: Ö
authors.lastname: Melefors
authors.forename: Ulrika
authors.initials: U
authors.lastname: Liljedahl
authors.forename: Lars
authors.initials: L
authors.lastname: Engstrand
authors.forename: Siv G E
authors.initials: SG
authors.lastname: Andersson
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics*; D018829:Adhesins, Bacterial / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004196:Disease Outbreaks; D024881:Drug Resistance, Bacterial / Q000235:genetics; D054324:Enterohemorrhagic Escherichia coli / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000453:epidemiology; D023061:Gene Order; D005798:Genes, Bacterial; D016680:Genome, Bacterial; D006463:Hemolytic-Uremic Syndrome / Q000453:epidemiology; D006801:Humans; D009154:Mutation; D010802:Phylogeny; D010957:Plasmids / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D039002:Prophages / Q000235:genetics; D040641:Quantitative Trait Loci; D011995:Recombination, Genetic; D022621:Shiga Toxin / Q000235:genetics; D013691:Tellurium / Q000494:pharmacology; D014416:Tunisia; D014774:Virulence / Q000235:genetics*
chemical_list: D018829:Adhesins, Bacterial; D000900:Anti-Bacterial Agents; D022621:Shiga Toxin; D013691:Tellurium