1887

Journal of Medical Microbiology logo

Volume 73, Issue 2

Clinical and public health implications of increasing notifications of LEE-negative Shiga toxin-producing in England, 2014–2022 Open Access

Abstract

Shiga toxin-producing (STEC) belong to a diverse group of gastrointestinal pathogens. The pathogenic potential of STEC is enhanced by the presence of the pathogenicity island called the Locus of Enterocyte Effacement (LEE), including the intimin encoding gene .

STEC serotypes O128:H2 (Clonal Complex [CC]25), O91:H14 (CC33), and O146:H21 (CC442) are consistently in the top five STEC serotypes isolated from patients reporting gastrointestinal symptoms in England. However, they are LEE-negative and perceived to be a low risk to public health, and we know little about their microbiology and epidemiology.

We analysed clinical outcomes and genome sequencing data linked to patients infected with LEE-negative STEC belonging to CC25 (O128:H2, O21:H2), CC33 (O91:H14) and, and CC442 (O146:H21, O174:H21) in England to assess the risk to public health.

There was an almost ten-fold increase between 2014 and 2022 in the detection of all STEC belonging to CC25, CC33 and CC442 (2014 =38, 2022 =336), and a total of 1417 cases. There was a higher proportion of female cases (55–70 %) and more adults than children, with patients aged between 20–40 and >70 most at risk across the different serotypes. Symptoms were consistent across the three dominant serotypes O91:H14 (CC33), O146:H21 (CC442) and O128:H2 (CC25) (diarrhoea >75 %; bloody diarrhoea 25–32 %; abdominal pain 64–72 %; nausea 37–45 %; vomiting 10–24 %; and fever 27–30 %). Phylogenetic analyses revealed multiple events of acquisition and loss of different stx-encoding prophage. Additional putative virulence genes were identified including , and .

Continued monitoring and surveillance of LEE-negative STEC infections is essential due to the increasing burden of infectious intestinal disease, and the risk that highly pathogenic strains may emerge following acquisition of the Shiga toxin subtypes associated with the most severe clinical outcomes.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): Epidemiology , Genome Sequencing , non-O157 STEC and Shiga toxin-producing Escherichia coli
Funding
This study was supported by the:
  • National Institute for Health Research Health Protection Research Unit (Award 111815)
    • Principle Award Recipient: ClaireJenkins
© 2024 Crown Copyright
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001790
2024-02-01
2024-04-27
Loading full text...

Full text loading...

/deliver/fulltext/jmm/73/2/jmm001790.html?itemId=/content/journal/jmm/10.1099/jmm.0.001790&mimeType=html&fmt=ahah

References

  1. Croxen MA, Law RJ, Scholz R, Keeney KM, Wlodarska M et al. Recent advances in understanding enteric pathogenic Escherichia coli. Clin Microbiol Rev 2013; 26:822–880 [View Article] [PubMed]
     [Google Scholar]
  2. Vishram B, Jenkins C, Greig DR, Godbole G, Carroll K et al. The emerging importance of Shiga toxin-producing Escherichia coli other than serogroup O157 in England. J Med Microbiol 2021; 70:001375 [View Article] [PubMed]
     [Google Scholar]
  3. Gentle A, Day MR, Hopkins KL, Godbole G, Jenkins C. Antimicrobial resistance in Shiga toxin-producing Escherichia coli other than serotype O157 : H7 in England, 2014–2016. J Med Microbiol 2020; 69:379–386 [View Article]
     [Google Scholar]
  4. Wirth T, Falush D, Lan R, Colles F, Mensa P et al. Sex and virulence in Escherichia coli: an evolutionary perspective. Mol Microbiol 2006; 60:1136–1151 [View Article] [PubMed]
     [Google Scholar]
  5. Jenkins C, Byrne L, Vishram B, Sawyer C, Balasegaram S et al. Shiga toxin-producing Escherichia coli haemolytic uraemic syndrome (STEC-HUS): diagnosis, surveillance and public-health management in England. J Med Microbiol 2020; 69:1034–1036 [View Article]
     [Google Scholar]
  6. Koutsoumanis K, Allende A, Alvarez‐Ordóñez A, Bover‐Cid S, Chemaly M et al. Pathogenicity assessment of Shiga toxin‐producing Escherichia coli (STEC) and the public health risk posed by contamination of food with STEC. EFS2 2020; 18: [View Article]
     [Google Scholar]
  7. Scheutz F, Teel LD, Beutin L, Piérard D, Buvens G et al. Multicenter evaluation of a sequence-based protocol for subtyping Shiga toxins and standardizing Stx nomenclature. J Clin Microbiol 2012; 50:2951–2963 [View Article] [PubMed]
     [Google Scholar]
  8. Bai X, Fu S, Zhang J, Fan R, Xu Y et al. Identification and pathogenomic analysis of an Escherichia coli strain producing a novel Shiga toxin 2 subtype. Sci Rep 2018; 8:6756 [View Article] [PubMed]
     [Google Scholar]
  9. Yang X, Bai X, Zhang J, Sun H, Fu S et al. Escherichia coli strains producing a novel Shiga toxin 2 subtype circulate in China. Int J Med Microbiol 2020; 310:151377 [View Article] [PubMed]
     [Google Scholar]
  10. Bai X, Scheutz F, Dahlgren HM, Hedenström I, Jernberg C. Characterization of clinical Escherichia coli strains producing a novel shiga toxin 2 subtype in Sweden and Denmark. Microorganisms 2021; 9:2374 [View Article] [PubMed]
     [Google Scholar]
  11. Gill A, Dussault F, McMahon T, Petronella N, Wang X et al. Characterization of atypical shiga toxin gene sequences and description of Stx2j, a new subtype. J Clin Microbiol 2022; 60:e0222921 [View Article] [PubMed]
     [Google Scholar]
  12. Lindsey RL, Prasad A, Feldgarden M, Gonzalez-Escalona N, Kapsak C et al. Identification and characterization of ten Escherichia coli strains encoding novel shiga toxin 2 subtypes, Stx2n as well as Stx2j, Stx2m, and Stx2o, in the United States. Microorganisms 2023; 11: [View Article] [PubMed]
     [Google Scholar]
  13. Byrne L, Adams N, Jenkins C. Association between shiga toxin-producing Escherichia coli O157:H7 stx gene subtype and disease severity, England, 2009-2019. Emerg Infect Dis 2020; 26:2394–2400 [View Article] [PubMed]
     [Google Scholar]
  14. Melton-Celsa AR, Darnell SC, O’Brien AD. Activation of shiga-like toxins by mouse and human intestinal mucus correlates with virulence of enterohemorrhagic Escherichia coli O91:H21 isolates in orally infected, streptomycin-treated mice. Infect Immun 1996; 64:1569–1576 [View Article] [PubMed]
     [Google Scholar]
  15. Bielaszewska M, Friedrich AW, Aldick T, Schürk-Bulgrin R, Karch H. Shiga toxin activatable by intestinal mucus in Escherichia coli isolated from humans: predictor for a severe clinical outcome. Clin Infect Dis 2006; 43:1160–1167 [View Article] [PubMed]
     [Google Scholar]
  16. Elliott SJ, Sperandio V, Girón JA, Shin S, Mellies JL et al. The locus of enterocyte effacement (LEE)-encoded regulator controls expression of both LEE- and non-LEE-encoded virulence factors in enteropathogenic and enterohemorrhagic Escherichia coli. Infect Immun 2000; 68:6115–6126 [View Article] [PubMed]
     [Google Scholar]
  17. Rodwell EV, Vishram B, Smith R, Browning L, Smith-Palmer A et al. Epidemiology and genomic analysis of shiga toxin-producing Escherichia coli clonal complex 165 in the UK. J Med Microbiol 2021; 70:001471 [View Article] [PubMed]
     [Google Scholar]
  18. Rodwell EV, Chan Y-W, Sawyer C, Carroll A, McNamara E et al. Shiga toxin-producing Escherichia coli clonal complex 32, including serotype O145:H28, in the UK and Ireland. J Med Microbiol 2022; 71: [View Article] [PubMed]
     [Google Scholar]
  19. Rodwell EV, Simpson A, Chan Y-W, Godbole G, McCarthy ND et al. The epidemiology of shiga toxin-producing Escherichia coli O26:H11 (clonal complex 29) in England, 2014-2021. J Infect 2023; 86:552–562 [View Article] [PubMed]
     [Google Scholar]
  20. Butt S, Allison L, Vishram B, Greig DR, Aird H et al. Epidemiological investigations identified an outbreak of shiga toxin-producing Escherichia coli serotype O26:H11 associated with pre-packed sandwiches. Epidemiol Infect 2021; 149:e178 [View Article] [PubMed]
     [Google Scholar]
  21. Jenkins C, Lawson AJ, Cheasty T, Willshaw GA. Assessment of a real-time PCR for the detection and characterization of verocytotoxigenic Escherichia coli. J Med Microbiol 2012; 61:1082–1085 [View Article] [PubMed]
     [Google Scholar]
  22. Feng PCH, Jinneman K, Scheutz F, Monday SR. Specificity of PCR and serological assays in the detection of Escherichia coli shiga toxin subtypes. Appl Environ Microbiol 2011; 77:6699–6702 [View Article] [PubMed]
     [Google Scholar]
  23. UKHSA Shiga toxin-producing Escherichia coli (STEC) data: 2020; 2023 https://www.gov.uk/government/publications/escherichia-coli-e-coli-o157-annual-totals/shiga-toxin-producing-escherichia-coli-stec-data-2020
  24. Mellmann A, Fruth A, Friedrich AW, Wieler LH, Harmsen D et al. Phylogeny and disease association of shiga toxin-producing Escherichia coli O91. Emerg Infect Dis 2009; 15:1474–1477 [View Article] [PubMed]
     [Google Scholar]
  25. Lee JB, Kim S-K, Wi SM, Cho Y-J, Hahn T-W et al. Molecular epidemiology of sequence type 33 of shiga toxin-producing Escherichia coli O91:H14 isolates from human patients and retail meats in Korea. J Vet Sci 2019; 20:87–90 [View Article] [PubMed]
     [Google Scholar]
  26. Nüesch-Inderbinen M, Stevens MJA, Cernela N, Müller A, Biggel M et al. Distribution of virulence factors, antimicrobial resistance genes and phylogenetic relatedness among Shiga toxin-producing Escherichia coli serogroup O91 from human infections. Int J Med Microbiol 2021; 311:151541 [View Article] [PubMed]
     [Google Scholar]
  27. Montero DA, Velasco J, Del Canto F, Puente JL, Padola NL et al. Locus of Adhesion and Autoaggregation (LAA), a pathogenicity island present in emerging shiga toxin-producing Escherichia coli strains. Sci Rep 2017; 7:7011 [View Article] [PubMed]
     [Google Scholar]
  28. Colello R, Vélez MV, González J, Montero DA, Bustamante AV et al. First report of the distribution of Locus of Adhesion and Autoaggregation (LAA) pathogenicity island in LEE-negative Shiga toxin-producing Escherichia coli isolates from Argentina. Microb Pathog 2018; 123:259–263 [View Article] [PubMed]
     [Google Scholar]
  29. Dias D, Costa S, Fonseca C, Baraúna R, Caetano T et al. Pathogenicity of shiga toxin-producing Escherichia coli (STEC) from wildlife: should we care?. Sci Total Environ 2022; 812:152324 [View Article] [PubMed]
     [Google Scholar]
  30. Montero DA, Canto FD, Velasco J, Colello R, Padola NL et al. Cumulative acquisition of pathogenicity islands has shaped virulence potential and contributed to the emergence of LEE-negative Shiga toxin-producing Escherichia coli strains. Emerg Microbes Infect 2019; 8:486–502 [View Article] [PubMed]
     [Google Scholar]
  31. Jenkins C, Perry NT, Godbole G, Gharbia S. Evaluation of chromogenic selective agar (CHROMagar STEC) for the direct detection of shiga toxin-producing Escherichia coli from faecal specimens. J Med Microbiol 2020; 69:487–491 [View Article] [PubMed]
     [Google Scholar]
  32. Chattaway MA, Dallman TJ, Gentle A, Wright MJ, Long SE et al. Whole genome sequencing for public health surveillance of shiga toxin-producing Escherichia coli other than serogroup O157. Front Microbiol 2016; 7:258 [View Article] [PubMed]
     [Google Scholar]
  33. Ashton PM, Perry N, Ellis R, Petrovska L, Wain J et al. Insight into shiga toxin genes encoded by Escherichia coli O157 from whole genome sequencing. PeerJ 2015; 3:e739 [View Article] [PubMed]
     [Google Scholar]
  34. Tewolde R, Dallman T, Schaefer U, Sheppard CL, Ashton P et al. MOST: a modified MLST typing tool based on short read sequencing. PeerJ 2016; 4:e2308 [View Article] [PubMed]
     [Google Scholar]
  35. Steyert SR, Sahl JW, Fraser CM, Teel LD, Scheutz F et al. Comparative genomics and stx phage characterization of LEE-negative shiga toxin-producing Escherichia coli. Front Cell Infect Microbiol 2012; 2:133 [View Article] [PubMed]
     [Google Scholar]
  36. Dallman T, Ashton P, Schafer U, Jironkin A, Painset A et al. SnapperDB: a database solution for routine sequencing analysis of bacterial isolates. Bioinformatics 2018; 34:3028–3029 [View Article] [PubMed]
     [Google Scholar]
  37. Croucher NJ, Page AJ, Connor TR, Delaney AJ, Keane JA et al. Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins. Nucleic Acids Res 2015; 43:e15 [View Article] [PubMed]
     [Google Scholar]
  38. Minh BQ, Schmidt HA, Chernomor O, Schrempf D, Woodhams MD et al. IQ-TREE 2: new models and efficient methods for phylogenetic inference in the genomic era. Mol Biol Evol 2020; 37:1530–1534 [View Article] [PubMed]
     [Google Scholar]
  39. Letunic I, Bork P. Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res 2021; 49:W293–W296 [View Article] [PubMed]
     [Google Scholar]
  40. UKHSA Public health operational guidance for Shiga toxin-producing Escherichia coli (STEC); 2023 https://www.gov.uk/government/publications/shiga-toxin-producing-escherichia-coli-public-health-management
  41. Carroll KJ, Jenkins C, Harvey-Vince L, Mohan K, Balasegaram S. Shiga toxin-producing Escherichia coli diagnosed by Stx PCR: assessing the public health risk of non-O157 strains. Eur J Public Health 2021; 31:576–582 [View Article] [PubMed]
     [Google Scholar]
  42. McCarthy SC, Macori G, Duggan G, Burgess CM, Fanning S et al. Prevalence and whole-genome sequence-based analysis of shiga toxin-producing Escherichia coli isolates from the recto-anal junction of slaughter-age Irish sheep. Appl Environ Microbiol 2021; 87:e0138421 [View Article] [PubMed]
     [Google Scholar]
  43. Treier A, Stephan R, Stevens MJA, Cernela N, Nüesch-Inderbinen M. High occurrence of shiga toxin-producing Escherichia coli in raw meat-based diets for companion animals-a public health issue. Microorganisms 2021; 9:1556 [View Article] [PubMed]
     [Google Scholar]
  44. Miko A, Pries K, Haby S, Steege K, Albrecht N et al. Assessment of shiga toxin-producing Escherichia coli isolates from wildlife meat as potential pathogens for humans. Appl Environ Microbiol 2009; 75:6462–6470 [View Article] [PubMed]
     [Google Scholar]
  45. Mora A, López C, Dhabi G, López-Beceiro AM, Fidalgo LE et al. Seropathotypes, phylogroups, Stx subtypes, and intimin types of wildlife-carried, shiga toxin-producing Escherichia coli strains with the same characteristics as human-pathogenic isolates. Appl Environ Microbiol 2012; 78:2578–2585 [View Article] [PubMed]
     [Google Scholar]
  46. Blanco J, Blanco M, Blanco JE, Mora A, González EA et al. Verotoxin-producing Escherichia coli in Spain: prevalence, serotypes, and virulence genes of O157:H7 and non-O157 VTEC in ruminants, raw beef products, and humans. Exp Biol Med 2003; 228:345–351 [View Article] [PubMed]
     [Google Scholar]
  47. Balière C, Rincé A, Blanco J, Dahbi G, Harel J et al. Prevalence and characterization of shiga toxin-producing and enteropathogenic Escherichia coli in shellfish-harvesting areas and their watersheds. Front Microbiol 2015; 6:1356 [View Article] [PubMed]
     [Google Scholar]
  48. Sánchez S, Beristain X, Martínez R, García A, Martín C et al. Subtilase cytotoxin encoding genes are present in human, sheep and deer intimin-negative, shiga toxin-producing Escherichia coli O128:H2. Vet Microbiol 2012; 159:531–535 [View Article] [PubMed]
     [Google Scholar]
  49. Son HM, Duc HM, Honjoh KI, Miyamoto T. Identification of the newly identified subtilase cytotoxin-encoding gene (subAB2-2) among clinical shiga toxin-producing Escherichia coli isolates. Can J Microbiol 2015; 61:990–994 [View Article] [PubMed]
     [Google Scholar]
  50. Liu Y, Li H, Chen X, Tong P, Zhang Y et al. Characterization of shiga toxin-producing Escherichia coli isolated from cattle and sheep in Xinjiang province, China, using whole-genome sequencing. Transbound Emerg Dis 2022; 69:413–422 [View Article] [PubMed]
     [Google Scholar]
  51. Brett KN, Ramachandran V, Hornitzky MA, Bettelheim KA, Walker MJ et al. stx1c Is the most common shiga toxin 1 subtype among shiga toxin-producing Escherichia coli isolates from sheep but not among isolates from cattle. J Clin Microbiol 2003; 41:926–936 [View Article] [PubMed]
     [Google Scholar]
  52. Dallman TJ, Greig DR, Gharbia SE, Jenkins C. Phylogenetic structure of shiga toxin-producing Escherichia coli O157:H7 from sub-lineage to SNPs. Microb Genom 2021; 7:mgen000544 [View Article] [PubMed]
     [Google Scholar]
  53. Dallman TJ, Greig DR, Gharbia SE, Jenkins C. Phylogenetic context of shiga toxin-producing Escherichia coli serotype O26:H11 in England. Microb Genom 2019; 7:000551 [View Article] [PubMed]
     [Google Scholar]
  54. Butt S, Jenkins C, Godbole G, Byrne L. The epidemiology of shiga toxin-producing Escherichia coli serogroup O157 in England, 2009-2019. Epidemiol Infect 2022; 150:e52 [View Article] [PubMed]
     [Google Scholar]
  55. Al Qabili DMA, Aboueisha A-KM, Ibrahim GA, Youssef AI, El-Mahallawy HS. Virulence and antimicrobial-resistance of shiga toxin-producing E. coli (STEC) Isolated from edible shellfish and its public health significance. Arch Microbiol 2022; 204:510 [View Article] [PubMed]
     [Google Scholar]
  56. Nguyen TTH, Kikuchi T, Tokunaga T, Iyoda S, Iguchi A. Diversity of the tellurite resistance gene operon in Escherichia coli. Front Microbiol 2021; 12:681175 [View Article] [PubMed]
     [Google Scholar]
  57. Taylor DE. Bacterial tellurite resistance. Trends Microbiol 1999; 7:111–115 [View Article] [PubMed]
     [Google Scholar]
  58. Zhang W, Nadirk J, Kossow A, Bielaszewska M, Leopold SR et al. Phylogeny and phenotypes of clinical and environmental shiga toxin-producing Escherichia coli O174. Environ Microbiol 2014; 16:963–976 [View Article] [PubMed]
     [Google Scholar]
  59. Commereuc M, Weill F-X, Loukiadis E, Gouali M, Gleizal A et al. Recurrent hemolytic and uremic syndrome induced by Escherichia coli. Medicine 2016; 95:e2050 [View Article] [PubMed]
     [Google Scholar]
  60. Friedrich AW, Bielaszewska M, Zhang W-L, Pulz M, Kuczius T et al. Escherichia coli harboring shiga toxin 2 gene variants: frequency and association with clinical symptoms. J Infect Dis 2002; 185:74–84 [View Article] [PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.001790
Loading
Clinical and public health implications of increasing notifications of LEE-negative Shiga toxin-producing Escherichia coli in England, 2014–2022
J. Med. Microbiol. 73, 001790 (2024); https://doi.org/10.1099/jmm.0.001790
/content/journal/jmm/10.1099/jmm.0.001790
/content/journal/jmm/10.1099/jmm.0.001790
Loading

Data & Media loading...

Supplements

Supplementary material 1

EXCEL

Supplementary material 2

PDF

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error