title: Origins of the E. coli strain causing an outbreak of hemolytic-uremic syndrome in Germany.
abstract: BACKGROUND
  A large outbreak of diarrhea and the hemolytic-uremic syndrome caused by an unusual serotype of Shiga-toxin-producing Escherichia coli (O104:H4) began in Germany in May 2011. As of July 22, a large number of cases of diarrhea caused by Shiga-toxin-producing E. coli have been reported--3167 without the hemolytic-uremic syndrome (16 deaths) and 908 with the hemolytic-uremic syndrome (34 deaths)--indicating that this strain is notably more virulent than most of the Shiga-toxin-producing E. coli strains. Preliminary genetic characterization of the outbreak strain suggested that, unlike most of these strains, it should be classified within the enteroaggregative pathotype of E. coli.
  
  
  METHODS
  We used third-generation, single-molecule, real-time DNA sequencing to determine the complete genome sequence of the German outbreak strain, as well as the genome sequences of seven diarrhea-associated enteroaggregative E. coli serotype O104:H4 strains from Africa and four enteroaggregative E. coli reference strains belonging to other serotypes. Genomewide comparisons were performed with the use of these enteroaggregative E. coli genomes, as well as those of 40 previously sequenced E. coli isolates.
  
  
  RESULTS
  The enteroaggregative E. coli O104:H4 strains are closely related and form a distinct clade among E. coli and enteroaggregative E. coli strains. However, the genome of the German outbreak strain can be distinguished from those of other O104:H4 strains because it contains a prophage encoding Shiga toxin 2 and a distinct set of additional virulence and antibiotic-resistance factors.
  
  
  CONCLUSIONS
  Our findings suggest that horizontal genetic exchange allowed for the emergence of the highly virulent Shiga-toxin-producing enteroaggregative E. coli O104:H4 strain that caused the German outbreak. More broadly, these findings highlight the way in which the plasticity of bacterial genomes facilitates the emergence of new pathogens.
authors.affiliation: University of Maryland School of Medicine, Institute for Genome Sciences and Department of Microbiology, Baltimore, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Rasko
authors.forename: Dale R
authors.initials: DR
authors.lastname: Webster
authors.forename: Jason W
authors.initials: JW
authors.lastname: Sahl
authors.forename: Ali
authors.initials: A
authors.lastname: Bashir
authors.forename: Nadia
authors.initials: N
authors.lastname: Boisen
authors.forename: Flemming
authors.initials: F
authors.lastname: Scheutz
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Paxinos
authors.forename: Robert
authors.initials: R
authors.lastname: Sebra
authors.forename: Chen-Shan
authors.initials: CS
authors.lastname: Chin
authors.forename: Dimitris
authors.initials: D
authors.lastname: Iliopoulos
authors.forename: Aaron
authors.initials: A
authors.lastname: Klammer
authors.forename: Paul
authors.initials: P
authors.lastname: Peluso
authors.forename: Lawrence
authors.initials: L
authors.lastname: Lee
authors.forename: Andrey O
authors.initials: AO
authors.lastname: Kislyuk
authors.forename: James
authors.initials: J
authors.lastname: Bullard
authors.forename: Andrew
authors.initials: A
authors.lastname: Kasarskis
authors.forename: Susanna
authors.initials: S
authors.lastname: Wang
authors.forename: John
authors.initials: J
authors.lastname: Eid
authors.forename: David
authors.initials: D
authors.lastname: Rank
authors.forename: Julia C
authors.initials: JC
authors.lastname: Redman
authors.forename: Susan R
authors.initials: SR
authors.lastname: Steyert
authors.forename: Jakob
authors.initials: J
authors.lastname: Frimodt-Møller
authors.forename: Carsten
authors.initials: C
authors.lastname: Struve
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Petersen
authors.forename: Karen A
authors.initials: KA
authors.lastname: Krogfelt
authors.forename: James P
authors.initials: JP
authors.lastname: Nataro
authors.forename: Eric E
authors.initials: EE
authors.lastname: Schadt
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Waldor
mesh_terms: D015373:Bacterial Typing Techniques; D001483:Base Sequence; D003967:Diarrhea / Q000453:epidemiology / Q000382:microbiology; D004196:Disease Outbreaks; D004927:Escherichia coli Infections / Q000453:epidemiology / Q000382:microbiology*; D005243:Feces / Q000382:microbiology; D005260:Female; D016680:Genome, Bacterial; D005858:Germany / Q000453:epidemiology; D006463:Hemolytic-Uremic Syndrome / Q000453:epidemiology / Q000382:microbiology*; D006801:Humans; D008875:Middle Aged; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D054323:Shiga-Toxigenic Escherichia coli / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification