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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. 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.
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Coli 55989 strain, in order to identify copy-number variations and small nucleotide variations among all the isolates (, and Table 3 and Fig. (See at NEJM.org.) The genomes of the isolates from the current outbreak (C227-11, TY2482, LB226692, and H112180280) were very similar, with only 236 differences in single-nucleotide variants detected between TY2482 and C227-11 (Table 3 and Fig. 3 in the ), suggesting that the outbreak is clonal. We observed structural variations between the C227-11 genome and the complete genome sequence of TY2482, based in part on the recently described draft assembly, that seem unlikely to be the result of misassemblies in the C227-11 genome, because these regions are identical in the C227-11 and H112180280 genomes (Fig. 4 and 5 in the ). However, we observed larger-scale deletions, insertions, inversions, and other structural variations between the O104:H4 outbreak isolates and the seven other enteroaggregative E. Coli O104:H4 isolates we sequenced ( ).


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