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Here, we reviewed the role hybrid STEC pathotypes have played in causing outbreaks of gastrointestinal infectious disease (GIID) from the epidemics of dysentery at the end of the 19th century, to recent foodborne outbreaks and outbreaks of haemolytic uraemic syndrome (HUS). We assessed genomic and epidemiological characteristics to determine the pathogenic potential, and likelihood of the emergence and spread, of each hybrid pathotype. Both STEC\/EPEC and STEC\/ETEC pathotypes are common, with hybrid STEC\/EPEC strains persistently causing a high clinical and public health burden of GIID over the last 40 years worldwide. STEC\/EAEC and STEC\/ExPEC hybrid strains appear to have emerged over the last decade and have caused clinically severe GIID in modern times. We concluded that hybrid pathotypes are most likely to occur between E. coli that persist in the animal reservoir, but that any type that can acquire bacteriophage encoding Shiga toxin, particularly subtypes stx2a and stx2d, can be a threat to public health, and may cause epidemics in vulnerable populations. Systematic surveillance of all E. coli pathotypes and the integration of clinical outcome data are essential to elucidating the factors that enable stable STEC hybrid clones to persist and propagate. Detection and analysis of emerging pathogenic strains will provide a better understanding of how to intervene and manage the risks.<\/jats:p>","DOI":"10.1093\/jambio\/lxaf250","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T11:44:26Z","timestamp":1760442266000},"source":"Crossref","is-referenced-by-count":6,"title":["Hybrid pathotypes of Shiga toxin-producing\n                    <i>Escherichia coli<\/i>"],"prefix":"10.1093","volume":"136","author":[{"given":"Claire","family":"Jenkins","sequence":"first","affiliation":[{"name":"UK Health Security Agency , London, NW9 5HT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie Anne","family":"Chattaway","sequence":"additional","affiliation":[{"name":"UK Health Security Agency , London, NW9 5HT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derren","family":"Ready","sequence":"additional","affiliation":[{"name":"UK Health Security Agency , London, NW9 5HT"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"2025101605073248200_bib99_874_145325","doi-asserted-by":"publisher","first-page":"590","DOI":"10.3201\/eid2204.151485","article-title":"Shiga Toxin-Producing Escherichia coli O157, England and Wales, 1983-2012","volume":"22","author":"Adams","year":"2016","journal-title":"Emerg Infect Dis"},{"key":"2025101605073248200_bib1","doi-asserted-by":"publisher","first-page":"5619","DOI":"10.1038\/s41598-019-42122-z","article-title":"Molecular characterization and comparative genomics of clinical hybrid shiga toxin-producing and enterotoxigenic Escherichia coli (STEC\/ETEC) strains in Sweden","volume":"9","author":"Bai","year":"2019","journal-title":"Sci Rep"},{"key":"2025101605073248200_bib2","doi-asserted-by":"publisher","first-page":"e000181","DOI":"10.1099\/mgen.0.000181","article-title":"An outbreak of a rare Shiga-toxin-producing Escherichia coli serotype (O117:H7) among men who have sex with men","volume-title":"Microb Genom","author":"Baker","year":"2018"},{"key":"2025101605073248200_bib3","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1099\/00222615-47-4-283","article-title":"The 18th C.L. 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