Origins of the E. coli strain causing an outbreak of hemolytic-uremic syndrome in Germany.
Origins of the E. coli strain causing an outbreak of hemolytic-uremic syndrome in Germany.
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DOI：
10.1056/nejmoa1106920
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发表时间：
2011-08-25
期刊：
影响因子：
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通讯作者：
Waldor MK
中科院分区：
文献类型：
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作者：
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年5月，德国开始爆发由一种不寻常的产志贺毒素大肠杆菌（O104:H4）血清型引起的腹泻和溶血性尿毒症综合征大暴发。截至7月22日，已报告了大量由产志贺毒素大肠杆菌引起的腹泻病例——3167例没有溶血性尿毒症综合征（16例死亡），908例有溶血性尿毒症综合征（34例死亡）——表明该菌株明显比大多数产志贺毒素大肠杆菌菌株更具毒性。暴发菌株的初步遗传特征表明，与大多数这些菌株不同，它应被归类为大肠杆菌的肠道聚集型。我们使用第三代单分子实时DNA测序技术确定了德国暴发菌株的全基因组序列，以及来自非洲的7株腹泻相关肠聚集性大肠杆菌血清型O104:H4菌株和4株属于其他血清型的肠聚集性大肠杆菌参考菌株的基因组序列。使用这些肠聚集性大肠杆菌基因组以及40个先前测序的大肠杆菌分离株进行全基因组比较。肠聚集性大肠杆菌O104:H4菌株亲缘关系密切，在大肠杆菌和肠聚集性大肠杆菌菌株中形成了一个独特的分支。然而，德国暴发菌株的基因组可以与其他O104:H4菌株的基因组区分开来，因为它含有编码志贺毒素2的前噬菌体和一组独特的附加毒力和抗生素抗性因子。我们的研究结果表明，水平遗传交换允许产生高毒力的产志贺毒素肠聚集性大肠杆菌O104:H4菌株的出现，该菌株引起了德国的疫情。更广泛地说，这些发现强调了细菌基因组的可塑性促进新病原体出现的方式。
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. 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. 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. 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.