Origins of the E. coli strain causing an outbreak of hemolytic-uremic syndrome in Germany

David A. Rasko; Dale R. Webster; Jason W. Sahl; Ali Bashir; Nadia Boisen; Flemming Scheutz; Ellen E. Paxinos; Robert Sebra; Chen Shan Chin; Dimitris Iliopoulos; Aaron Klammer; Paul Peluso; Lawrence Lee; Andrey O. Kislyuk; James Bullard; Andrew Kasarskis; Susanna Wang; John Eid; David Rank; Julia C. Redman; Susan R. Steyert; Jakob Frimodt-Møller; Carsten Struve; Andreas M. Petersen; Karen A. Krogfelt; James P. Nataro; Eric E. Schadt; Matthew K. Waldor

doi:10.1056/nejmoa1106920

Origins of the E. coli strain causing an outbreak of hemolytic-uremic syndrome in Germany

David A. Rasko, Dale R. Webster, Jason W. Sahl, Ali Bashir, Nadia Boisen, Flemming Scheutz, Ellen E. Paxinos, Robert Sebra, Chen Shan Chin, Dimitris Iliopoulos, Aaron Klammer, Paul Peluso, Lawrence Lee, Andrey O. Kislyuk, James Bullard, Andrew Kasarskis, Susanna Wang, John Eid, David Rank, Julia C. RedmanSusan R. Steyert, Jakob Frimodt-Møller, Carsten Struve, Andreas M. Petersen, Karen A. Krogfelt, James P. Nataro, Eric E. Schadt^*, Matthew K. Waldor

^*Corresponding author for this work

607 Citations (Scopus)

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.

Original language	English
Journal	New England Journal of Medicine
Volume	365
Issue number	8
Pages (from-to)	709-717
Number of pages	9
ISSN	0028-4793
DOIs	https://doi.org/10.1056/nejmoa1106920
Publication status	Published - 25 Aug 2011

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Rasko, D. A., Webster, D. R., Sahl, J. W., Bashir, A., Boisen, N., Scheutz, F., Paxinos, E. E., Sebra, R., Chin, C. S., Iliopoulos, D., Klammer, A., Peluso, P., Lee, L., Kislyuk, A. O., Bullard, J., Kasarskis, A., Wang, S., Eid, J., Rank, D., ... Waldor, M. K. (2011). Origins of the E. coli strain causing an outbreak of hemolytic-uremic syndrome in Germany. New England Journal of Medicine, 365(8), 709-717. https://doi.org/10.1056/nejmoa1106920

Rasko, DA, Webster, DR, Sahl, JW, Bashir, A, Boisen, N, Scheutz, F, Paxinos, EE, Sebra, R, Chin, CS, Iliopoulos, D, Klammer, A, Peluso, P, Lee, L, Kislyuk, AO, Bullard, J, Kasarskis, A, Wang, S, Eid, J, Rank, D, Redman, JC, Steyert, SR, Frimodt-Møller, J, Struve, C, Petersen, AM, Krogfelt, KA, Nataro, JP, Schadt, EE & Waldor, MK 2011, 'Origins of the E. coli strain causing an outbreak of hemolytic-uremic syndrome in Germany', New England Journal of Medicine, vol. 365, no. 8, pp. 709-717. https://doi.org/10.1056/nejmoa1106920

@article{241eae837c5445fdba93e36c8cd3b60d,

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.",

author = "Rasko, {David A.} and Webster, {Dale R.} and Sahl, {Jason W.} and Ali Bashir and Nadia Boisen and Flemming Scheutz and Paxinos, {Ellen E.} and Robert Sebra and Chin, {Chen Shan} and Dimitris Iliopoulos and Aaron Klammer and Paul Peluso and Lawrence Lee and Kislyuk, {Andrey O.} and James Bullard and Andrew Kasarskis and Susanna Wang and John Eid and David Rank and Redman, {Julia C.} and Steyert, {Susan R.} and Jakob Frimodt-M{\o}ller and Carsten Struve and Petersen, {Andreas M.} and Krogfelt, {Karen A.} and Nataro, {James P.} and Schadt, {Eric E.} and Waldor, {Matthew K.}",

year = "2011",

month = aug,

day = "25",

doi = "10.1056/nejmoa1106920",

language = "English",

volume = "365",

pages = "709--717",

journal = "New England Journal of Medicine",

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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.

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U2 - 10.1056/nejmoa1106920

DO - 10.1056/nejmoa1106920

M3 - Journal 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 -

Origins of the E. coli strain causing an outbreak of hemolytic-uremic syndrome in Germany

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