Chapter 4 : Enterohemorrhagic Genomics: Past, Present, and Future

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O157:H7 is the most common enterohemorrhagic (EHEC) serotype in North America, and it has been the principal causative agent of numerous food-poisoning outbreaks worldwide ( ). Initially O157:H7 was recognized as a human pathogen in 1982 when it was isolated from 47 persons in two states who had developed bloody diarrhea after consuming hamburgers contaminated with this organism ( ). Since then, O157:H7 has emerged as a major enteric pathogen, capable of causing localized infections and large outbreaks of gastrointestinal disease ( ). Data accumulated from 1982 to 1996 showed that approximately two-thirds of the 3,000 cases of infections from 139 recognized outbreaks were associated with the ingestion of contaminated food products, whereas 22% of the reported cases were from direct person-to-person transmission and 10% were from drinking water ( ). Surveillance data have demonstrated a high prevalence of O157:H7 among cattle and their environment, but a relatively low incidence of human infection. This supports the potential hypothesis that a subset of O157:H7 harbored in cattle may be responsible for the majority of human disease ( ). To minimize or eradicate adverse effects on public health, the O157:H7 lineage has been the focus of numerous epidemiological, microbiological, genomic, forensic, and diagnostic studies. Overall, it is estimated that O157:H7 alone causes more than 76,000 infections and 61 deaths in humans due to severe complications annually in the United States ( ). Symptoms include a range of gastrointestinal morbidities, such as severe abdominal cramping accompanied with little or no associated fever and a watery diarrhea that leads to severe bloody diarrhea ( ). Although many infected individuals remain asymptomatic, approximately 15 to 20% of people infected with EHEC present severe enough symptoms to require hospitalization. In such severe cases, patients display renal dysfunction known as hemolytic-uremic syndrome (HUS), hemorrhagic colitis, and central nervous system failure with potentially lethal outcomes ( ).

Citation: Sadiq S, Hazen T, Rasko D, Eppinger M. 2015. Enterohemorrhagic Genomics: Past, Present, and Future, p 75-95. In Sperandio V, Hovde C (ed), Enterohemorrhagic and Other Shiga Toxin-Producing . ASM Press, Washington, DC. doi: 10.1128/microbiolspec.EHEC-0020-2013
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Figure 1

Figure depicts the molecular differences that define each of the attaching and effacing . The gene encodes the intimin protein on the LEE region; the gene in this case is the presence of the bundle-forming pilus operon, and the gene encodes the Shiga toxin. These three features are classically used to define the pathotypes, including EHEC.

Citation: Sadiq S, Hazen T, Rasko D, Eppinger M. 2015. Enterohemorrhagic Genomics: Past, Present, and Future, p 75-95. In Sperandio V, Hovde C (ed), Enterohemorrhagic and Other Shiga Toxin-Producing . ASM Press, Washington, DC. doi: 10.1128/microbiolspec.EHEC-0020-2013
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Image of Figure 2
Figure 2

Phylogeny of reference isolates, including EHEC. The reference used for the SNP calling is HS as a true commensal isolate ( ). The tree is maximum likelihood with 100 bootstraps made using RAxML, as previously described ( ). This figure highlights, as does MLST, that when compared to a large and diverse collection of isolates, EHEC, and specifically the O157 and O55 (in red and purple) and other serotypes (highlighted in yellow), demonstrates a high level of similarity. This high-level of similarity extends within these groups. Only once these clades are examined in detail can one begin to identify regions that are diagnostic in these clades.

Citation: Sadiq S, Hazen T, Rasko D, Eppinger M. 2015. Enterohemorrhagic Genomics: Past, Present, and Future, p 75-95. In Sperandio V, Hovde C (ed), Enterohemorrhagic and Other Shiga Toxin-Producing . ASM Press, Washington, DC. doi: 10.1128/microbiolspec.EHEC-0020-2013
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Figure 3

Phylogeny of O157 reference isolates demonstrating that there is variation within the O157 clade that is not observed in the larger genomic comparisons. This multi-whole genome alignment contains 4,093,272 bp of sequence. The tree is maximum likelihood with 100 bootstraps made using RAxML, as previously described ( ). The color indicates distinguishable clades within this selection of 50 EHEC isolates. The additional numbers in parentheses are the clade and LSPA designations, as described in the text.

Citation: Sadiq S, Hazen T, Rasko D, Eppinger M. 2015. Enterohemorrhagic Genomics: Past, Present, and Future, p 75-95. In Sperandio V, Hovde C (ed), Enterohemorrhagic and Other Shiga Toxin-Producing . ASM Press, Washington, DC. doi: 10.1128/microbiolspec.EHEC-0020-2013
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