Location: Meat Safety and QualityTitle: Shiga toxin sub-type 2a increases the efficiency of Escherichia coli O157 transmission between animals and restricts epithelial regeneration in bovine enteroids
|FITZGERALD, STEPHEN - Roslin Institute|
|BECKETT, AMY - Roslin Institute|
|PALAREA-ALBALADEJO, JAVIER - Biomathematics And Statistics Scotland (BIOSS)|
|MCATEER, SEAN - Roslin Institute|
|SHAABAN, SHARIF - Roslin Institute|
|MORGAN, JASON - Roslin Institute|
|AHMAD, NUR - Universiti Putra Malaysia|
|YOUNG, RACHEL - Roslin Institute|
|MABBOTT, NEIL - Roslin Institute|
|MORRISON, LIAM - Roslin Institute|
|Bono, James - Jim|
|GALLY, DAVID - Roslin Institute|
|MCNEILLY, TOM - Moredun Research Institute|
Submitted to: PLoS Pathogens
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/16/2019
Publication Date: 10/3/2019
Citation: Fitzgerald, S.F., Beckett, A.E., Palarea-Albaladejo, J., McAteer, S., Shaaban, S., Morgan, J., Ahmad, N.I., Young, R., Mabbott, N.A., Morrison, L., Bono, J.L., Gally, D.L., McNeilly, T.N. 2019. Shiga toxin sub-type 2a increases the efficiency of Escherichia coli O157 transmission between animals and restricts epithelial regeneration in bovine enteroids. PLoS Pathogens. 15(10):e1008003. https://doi.org/10.1371/journal.ppat.1008003.
Interpretive Summary: Shiga toxin-containing Escherichia coli O157:H7 (STEC O157) is a bacterium that can cause severe diarrhea, bloody diarrhea, and kidney failure in humans. Zoonotic infections with Escherichia coli O157:H7 have emerged as a serious threat to human health in the last three decades. Cattle are a natural reservoir for STEC O157 strains where they are asymptomatic. Reducing the transmission of STEC O157 between cattle would result in less STEC O157 in cattle herds and subsequently reduced human exposure. Challenge studies in cattle showed that Stx2a was essential for transmission between actively shedding and sentinel calves. The results of this study demonstrate that Shiga toxin subtype 2a (Stx2a) may provide a new target for reducing STEC O157 transmission in cattle.
Technical Abstract: 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 (>10**3** 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 Stx2cencoding 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.