Hybrid Strains of Enterotoxigenic/Shiga Toxin-producing , United Kingdom, 2014-2023

Overview

Journal J Med Microbiol

Date 2025 Jan 22

PMID 39841513

Authors

Ella V Rodwell

David R Greig

Suzanne Gokool

Israel Olonade

Craig Swift

Yung-Wai Chan

Claire Jenkins

Affiliations

Soon will be listed here.

Abstract

Diarrhoeagenic (DEC) pathotypes are defined by genes located on mobile genetic elements, and more than one definitive pathogenicity gene may be present in the same strain. In August 2022, UK Health Security Agency (UKHSA) surveillance systems detected an outbreak of hybrid Shiga toxin-producing /enterotoxigenic (STEC-ETEC) serotype O101:H33 harbouring both Shiga toxin () and heat-stable toxin (). These hybrid strains of DEC are a public health concern, as they are often associated with enhanced pathogenicity. However, little is known about their epidemiology, clinical significance and associated public health burden. The aim of this study was to describe the microbiology, epidemiology and genomic analysis of this novel hybrid serotype in the context of the STEC-ETEC strains in the UKHSA archive. From 2014 to 2023, STEC isolated from faecal specimens testing positive for STEC by PCR were sequenced on the NextSeq 1000 short read platform and a subset were selected for long read nanopore sequencing. Genomes were analysed to determine serotype, subtype, DEC pathogenicity genes and antimicrobial resistance determinants. There were 162 STEC-ETEC strains isolated between 2014 and 2023, of which 117/162 were human clinical isolates and 45 were of food or animal origin. An average of 16 STEC-ETEC strains were identified each year, exhibiting a range of different subtypes, the most common profiles being (=65, 40%) and (=48, 30%). The most common sequence types were ST329 and ST200 (=24 each), and the most frequently detected serotype was O187:H28 (=25). Nine cases of genetically linked STEC-ETEC O101:H33, were detected between 8 August and 21 September 2022. Although the temporal and geographical distribution of the cases was characteristic of a foodborne outbreak, the contaminated vehicle was not identified. Phylogenetic analysis and long-read sequencing of the outbreak strain provided insight into the stepwise acquisition of and and the evolutionary history of STEC-ETEC pathotypes. The integration of epidemiological data and whole-genome sequencing for routine surveillance of gastrointestinal pathogens is key to understanding the emergence of zoonotic hybrid DEC pathotypes and monitoring foodborne threats to public health.

References

Lauzi S, Luzzago C, Chiani P, Michelacci V, Knijn A, Pedrotti L . Free-ranging red deer (Cervus elaphus) as carriers of potentially zoonotic Shiga toxin-producing Escherichia coli. Transbound Emerg Dis. 2021; 69(4):1902-1911. PMC: 9540879. DOI: 10.1111/tbed.14178. View

Greig D, Quinn O, Rodwell E, Olonade I, Swift C, Douglas A . Genomic analysis of an outbreak of Shiga toxin-producing O183:H18 in the United Kingdom, 2023. Microb Genom. 2024; 10(5). PMC: 11165631. DOI: 10.1099/mgen.0.001243. View

Kolenda R, Burdukiewicz M, Schierack P . A systematic review and meta-analysis of the epidemiology of pathogenic Escherichia coli of calves and the role of calves as reservoirs for human pathogenic E. coli. Front Cell Infect Microbiol. 2015; 5:23. PMC: 4357325. DOI: 10.3389/fcimb.2015.00023. View

Bai X, Zhang J, Ambikan A, Jernberg C, Ehricht R, Scheutz F . Molecular Characterization and Comparative Genomics of Clinical Hybrid Shiga Toxin-Producing and Enterotoxigenic Escherichia coli (STEC/ETEC) Strains in Sweden. Sci Rep. 2019; 9(1):5619. PMC: 6449507. DOI: 10.1038/s41598-019-42122-z. View

Den Ouden A, Greig D, Rodwell E, Tripodo F, Olonade I, Swift C . encoding Shiga toxin subtype Stx2f causing human infections in England, 2015-2022. J Med Microbiol. 2023; 72(6). DOI: 10.1099/jmm.0.001707. View

Nataro J, Kaper J . Diarrheagenic Escherichia coli. Clin Microbiol Rev. 1998; 11(1):142-201. PMC: 121379. DOI: 10.1128/CMR.11.1.142. View

Vishram B, Jenkins C, Greig D, Godbole G, Carroll K, Balasegaram S . The emerging importance of Shiga toxin-producing other than serogroup O157 in England. J Med Microbiol. 2021; 70(7). PMC: 8493422. DOI: 10.1099/jmm.0.001375. View

Jenkins C . Enteroaggregative Escherichia coli. Curr Top Microbiol Immunol. 2018; 416:27-50. DOI: 10.1007/82_2018_105. View

Dallman T, Neuert S, Fernandez Turienzo C, Berin M, Richardson E, Fuentes-Utrilla P . Prevalence and Persistence of Antibiotic Resistance Determinants in the Gut of Travelers Returning to the United Kingdom is Associated with Colonization by Pathogenic Escherichia coli. Microbiol Spectr. 2023; 11(4):e0518522. PMC: 10433802. DOI: 10.1128/spectrum.05185-22. View

10.

Newitt S, MacGregor V, Robbins V, Bayliss L, Chattaway M, Dallman T . Two Linked Enteroinvasive Escherichia coli Outbreaks, Nottingham, UK, June 2014. Emerg Infect Dis. 2016; 22(7):1178-84. PMC: 4918187. DOI: 10.3201/eid2207.152080. View

11.

Nyholm O, Heinikainen S, Pelkonen S, Hallanvuo S, Haukka K, Siitonen A . Hybrids of Shigatoxigenic and Enterotoxigenic Escherichia coli (STEC/ETEC) Among Human and Animal Isolates in Finland. Zoonoses Public Health. 2015; 62(7):518-24. DOI: 10.1111/zph.12177. View

12.

Chattaway M, Dallman T, Gentle A, Wright M, Long S, Ashton P . Whole Genome Sequencing for Public Health Surveillance of Shiga Toxin-Producing Escherichia coli Other than Serogroup O157. Front Microbiol. 2016; 7:258. PMC: 4776118. DOI: 10.3389/fmicb.2016.00258. View

13.

Yang X, Wu Y, Liu Q, Sun H, Luo M, Xiong Y . Genomic Characteristics of Stx2e-Producing Strains Derived from Humans, Animals, and Meats. Pathogens. 2021; 10(12). PMC: 8705337. DOI: 10.3390/pathogens10121551. View

14.

Hazen T, Michalski J, Luo Q, Shetty A, Daugherty S, Fleckenstein J . Comparative genomics and transcriptomics of Escherichia coli isolates carrying virulence factors of both enteropathogenic and enterotoxigenic E. coli. Sci Rep. 2017; 7(1):3513. PMC: 5471185. DOI: 10.1038/s41598-017-03489-z. View

15.

Dallman T, Byrne L, Ashton P, Cowley L, Perry N, Adak G . Whole-genome sequencing for national surveillance of Shiga toxin-producing Escherichia coli O157. Clin Infect Dis. 2015; 61(3):305-12. PMC: 4542925. DOI: 10.1093/cid/civ318. View

16.

Ji X, Liang B, Sun Y, Zhu L, Zhou B, Guo X . An Extended-Spectrum Beta-Lactamase-Producing Hybrid Shiga-Toxigenic and Enterotoxigenic Strain Isolated from a Piglet with Diarrheal Disease in Northeast China. Foodborne Pathog Dis. 2020; 17(6):382-387. DOI: 10.1089/fpd.2019.2720. View

17.

Johura F, Parveen R, Islam A, Sadique A, Rahim M, Monira S . Occurrence of Hybrid Strains Carrying Shiga Toxin and Heat-Stable Toxin in Livestock of Bangladesh. Front Public Health. 2017; 4:287. PMC: 5221120. DOI: 10.3389/fpubh.2016.00287. View

18.

Croxen M, Law R, Scholz R, Keeney K, Wlodarska M, Finlay B . Recent advances in understanding enteric pathogenic Escherichia coli. Clin Microbiol Rev. 2013; 26(4):822-80. PMC: 3811233. DOI: 10.1128/CMR.00022-13. View

19.

Njamkepo E, Fawal N, Tran-Dien A, Hawkey J, Strockbine N, Jenkins C . Erratum: Global phylogeography and evolutionary history of Shigella dysenteriae type 1. Nat Microbiol. 2016; 1(11):16209. DOI: 10.1038/nmicrobiol.2016.209. View

20.

Aref N, Abdel-Raheem A, Kamaly H, Hussien S . Clinical and sero-molecular characterization of with an emphasis on hybrid strain in healthy and diarrheic neonatal calves in Egypt. Open Vet J. 2018; 8(4):351-359. PMC: 6203894. DOI: 10.4314/ovj.v8i4.1. View