E. coli toxin responsible for life-threatening bacterial disease in humans

Published: 4 October 2019

Rapid production of an E. coli toxin that promotes gut colonisation in cattle is responsible for the emergence of a life-threatening bacterial disease in humans.

A new study published today in PLOS Pathogens by scientists at the Moredun Research Institute, the University of Edinburgh, Biomathematics and Statistics Scotland and international partners, has shown that a specific toxin produced by naturally-occurring E. coli bacteria helps these bacteria colonise the intestinal tract of cattle and increases transmission of the bacteria to other animals in the herd.

Rapid and high levels of expression of the toxin also means that when humans are infected they are more likely to suffer more serious symptoms. These toxin properties help explain the emergence of this dangerous human pathogen over the last 40 years.

Escherichia coli (E. coli) is a group of bacteria that makes up part of the natural gut flora of healthy humans and some animals. While many strains are harmless, some are known to cause serious disease in animals and humans.

Enterohaemorrhagic E. coli (EHEC) O157 are a subset of E. coli that are present in the gastrointestinal tract of cattle but cause no discernible disease in these animals. However, EHEC O157 excreted in the faeces of infected cattle can be passed on to humans through exposure to contaminated water, meat or vegetables.

EHEC produce toxins known as Shiga toxins of various sub-types. These toxins can cause a variety of diseases in humans by attacking the lining of blood vessels within the body, from diarrhoea with or without blood to more severe and potentially fatal kidney disease. The most dangerous toxin subtype to humans is subtype 2a (Stx2a).

"Our study shows for the first time that Stx2a toxin plays a key role in allowing E. coli O157 to colonise the cattle gut, increasing the ability of Stx2a positive bacteria to transmit between animals and shed at high levels into the environment. This matters because most human infections are thought to originate from cattle, and infections with E. coli O157 strains containing Stx2a are associated with more severe forms of human disease."

Dr Tom McNeilly, Moredun Research Institute

The study, involving a collaboration between scientists at Moredun Research Institute, the Roslin Institute (University of Edinburgh), Biomathematics and Statistics Scotland and international partners, investigated the role of Stx2a in colonisation of the cattle gut. It showed that Stx2a plays a critical role in increasing transmission of EHEC O157 between cattle due to a combination of two factors: firstly, Stx2a is produced more rapidly by the bacteria than other Shiga toxins and secondly, Stx2a promotes persistence of the bacteria on cells which line the gastro-intestinal tract of cattle by reducing their turnover rate.

This essentially allows infected cells to survive for longer. This makes it more likely that the cattle will shed the bacteria in their faeces for longer and at higher levels, and thus increasing the chance that the bacteria can be passed to other cattle in the herd as well as to humans.

“The study is important as it explains firstly why the Stx2a subtype has become common in E. coli O157 strains, the answer being that it can be produced more rapidly compared to some other Stx subtypes. Secondly, our work demonstrates how the toxin can provide an advantage in the animal host, basically by halting the usual turnover of gut cells that would remove adherent E. coli; so the bacteria colonise more easily, persist in the gut and can be excreted at high levels to go onto infect other animals and possibly humans”.

Prof David Gally, The Roslin Institute

“We modelled all critical aspects of bacterial shedding, antibody response and transmission data, which made it possible to distinguish genuine signals from biological noise and establish a solid framework for future research. This study illustrates how rigorous experimental design, coupled with advanced data analysis and modelling expertise, is fundamental to successful scientific discovery."

Dr Javier Palarea, Biomathematics and Statistics Scotland (BioSS)

The work demonstrates the advantage of Shiga toxins within the ruminant animal system. Ongoing work between these partners has developed a vaccine for use in cattle that has recently obtained commercial backing for a field trial.

The original study was funded by the Food Standards Agency/Food Standards Scotland.



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