Role of Shiga toxin sub-type 2a on the efficiency of Escherichia coli O157 infection

Scientists at The University of Edinburgh in the UK found that a toxin produced by naturally-occurring Enterohaemorrhagic E. coli (EHEC) O157 strains helps the bacteria colonize the intestinal tract of cattle and increases the transmission of the bacteria to other animals in the herd. EHEC O157 strains are found in asymptomatic cattle, while human exposure can lead to severe symptoms. The most dangerous symptoms in humans are associated with isolates that encode Stx subtype 2a. The study showed that rapid and high levels of toxin expression result in that infected people are likely to have more serious symptoms. The Stx2a did not alter excretion levels, and it enabled colonization of E. coli in animals. Rapid production of Stx2a and its role in establishing E. coli O157 colonization in the bovine gastrointestinal tract facilitate effective transmission and have led to its expansion in the cattle E. coli O157 population. Stx2a is produced quicker by the bacteria than other Shiga toxins, and it promotes the persistence of the bacteria on cells that line the gastrointestinal tract of cattle. This allows infected cells to survive for longer and makes it more likely the cattle will shed the bacteria in their feces for longer and at higher levels. Therefore, it increases the chance that bacteria can be passed to other cattle in the herd as well as to humans. The study demonstrates how the toxin can provide an advantage in the animal host, by halting the usual turnover of gut cells that would remove adherent E. coli. As a result, the bacteria colonize more easily, in the gut, and can be excreted at high levels to go onto infect other animals and possibly humans. @ https://journals.plos.org/plospathogens/article/authors?id=10.1371/journal.ppat.1008003

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

Author summary Enterohaemorrhagic E. coli (EHEC) O157 strains are found in cattle where they are asymptomatic, while human exposure can lead to severe symptoms including bloody diarrhoea and kidney damage due to the activity of Shiga toxin (Stx). The most serious symptoms in humans are associated with isolates that encode Stx subtype 2a. The advantage of these toxins in the animal reservoir is still not clear, however there is experimental evidence implicating Stx with increased bacterial adherence, immune modulation and suppression of predatory protozoa. In this study, the hypothesis that Stx2a is important for super-shedding and calf-to-calf transmission was tested by comparing excretion and transmission dynamics of E. coli O157 strains with and without Stx2a. While Stx2a did not alter excretion levels when calfs were orally challenge, it enabled colonisation of more in contact ‘sentinel’ animals in our transmission model. We show that Stx2a is generally induced more rapidly than Stx2c, resulting in increased levels of Stx2a expression. Both Stx2a and Stx2c were able to restrict cellular proliferation of epithelial cells in cultured bovine enteroids. Taken together, we propose that rapid production of Stx2a and its role in establishing E. coli O157 colonisation in the bovine gastrointestinal tract facilitate effective transmission and have led to its expansion in the cattle E. coli O157 population.

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