Shiga toxin sub-type 2a increases the efficiency of Escherichia coli O157 transmission between animals and restricts epithelial regeneration in bovine enteroids

Autoři: Stephen F. Fitzgerald aff001;  Amy E. Beckett aff001;  Javier Palarea-Albaladejo aff003;  Sean McAteer aff001;  Sharif Shaaban aff001;  Jason Morgan aff001;  Nur Indah Ahmad aff004;  Rachel Young aff001;  Neil A. Mabbott aff001;  Liam Morrison aff001;  James L. Bono aff005;  David L. Gally aff001;  Tom N. McNeilly aff002
Působiště autorů: Division of Immunity and Infection, The Roslin Institute and R(D)SVS, The University of Edinburgh, Midlothian, United Kingdom aff001;  Moredun Research Institute, Penicuik, United Kingdom aff002;  Biomathematics and Statistics Scotland, Edinburgh, United Kingdom aff003;  Universiti Putra Malaysia, Selangor Darul Ehsan, Malaysia aff004;  United States Department of Agriculture, Agricultural Research Service, Nebraska, United States of America aff005
Vyšlo v časopise: Shiga toxin sub-type 2a increases the efficiency of Escherichia coli O157 transmission between animals and restricts epithelial regeneration in bovine enteroids. PLoS Pathog 15(10): e32767. doi:10.1371/journal.ppat.1008003
Kategorie: Research Article


Specific Escherichia coli isolates lysogenised with prophages that express Shiga toxin (Stx) can be a threat to human health, with cattle being an important natural reservoir. In many countries the most severe pathology is associated with enterohaemorrhagic E. coli (EHEC) serogroups that express Stx subtype 2a. In the United Kingdom, phage type (PT) 21/28 O157 strains have emerged as the predominant cause of life-threatening EHEC infections and this phage type commonly encodes both Stx2a and Stx2c toxin types. PT21/28 is also epidemiologically linked to super-shedding (>103 cfu/g of faeces) which is significant for inter-animal transmission and human infection as demonstrated using modelling studies. We demonstrate that Stx2a is the main toxin produced by stx2a+/stx2c+ PT21/28 strains induced with mitomycin C and this is associated with more rapid induction of gene expression from the Stx2a-encoding prophage compared to that from the Stx2c-encoding prophage. Bacterial supernatants containing either Stx2a and/or Stx2c were demonstrated to restrict growth of bovine gastrointestinal organoids with no restriction when toxin production was not induced or prevented by mutation. Isogenic strains that differed in their capacity to produce Stx2a were selected for experimental oral colonisation of calves to assess the significance of Stx2a for both super-shedding and transmission between animals. Restoration of Stx2a expression in a PT21/28 background significantly increased animal-to-animal transmission and the number of sentinel animals that became super-shedders. We propose that while both Stx2a and Stx2c can restrict regeneration of the epithelium, it is the relatively rapid and higher levels of Stx2a induction, compared to Stx2c, that have contributed to the successful emergence of Stx2a+ E. coli isolates in cattle in the last 40 years. We propose a model in which Stx2a enhances E. coli O157 colonisation of in-contact animals by restricting regeneration and turnover of the colonised gastrointestinal epithelium.

Klíčová slova:

Bacteriophages – Cattle – Excretion – Gastrointestinal tract – Lysis (medicine) – Molting – Toxins – Organoids


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