TY - JOUR
T1 - Origins of the E. coli strain causing an outbreak of hemolytic-uremic syndrome in Germany
AU - Rasko, David A.
AU - Webster, Dale R.
AU - Sahl, Jason W.
AU - Bashir, Ali
AU - Boisen, Nadia
AU - Scheutz, Flemming
AU - Paxinos, Ellen E.
AU - Sebra, Robert
AU - Chin, Chen Shan
AU - Iliopoulos, Dimitris
AU - Klammer, Aaron
AU - Peluso, Paul
AU - Lee, Lawrence
AU - Kislyuk, Andrey O.
AU - Bullard, James
AU - Kasarskis, Andrew
AU - Wang, Susanna
AU - Eid, John
AU - Rank, David
AU - Redman, Julia C.
AU - Steyert, Susan R.
AU - Frimodt-Møller, Jakob
AU - Struve, Carsten
AU - Petersen, Andreas M.
AU - Krogfelt, Karen A.
AU - Nataro, James P.
AU - Schadt, Eric E.
AU - Waldor, Matthew K.
PY - 2011/8/25
Y1 - 2011/8/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=80052150179&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1106920
DO - 10.1056/NEJMoa1106920
M3 - Article
C2 - 21793740
AN - SCOPUS:80052150179
SN - 0028-4793
VL - 365
SP - 709
EP - 717
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 8
ER -