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).
Dr Tom McNeilly, Moredun Research Institute said:
"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."
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.
Prof David Gally, Roslin Institute said:
“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”.
Dr Javier Palarea, BioSS, said:
“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.”
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.
Moredun Research Institute
conducts internationally recognised research on the infectious diseases of livestock, caused by important viruses, bacteria and parasites. It employs 170 scientists, vets and support staff who continue to help find solutions for major challenges to modern farming such as the consequences of a changing climate; ensuring safe and sustainable food and water supplies conserving biodiversity and finding solutions to infectious disease. Today, many of the veterinary medicines and vaccines that are routinely used on farm have either been researched, developed or tested at Moredun. More information about the work of Moredun Research Institute can be found at www.moredun.ac.uk
The Roslin Institute
's mission is to gain fundamental understanding of genetic, cellular, organ and systems bioscience underpinning common mechanisms of animal development and pathology, and to use this knowledge to prevent and treat important veterinary diseases and develop sustainable farm animal production systems. The Institute receives strategic investment funding from the Biotechnology and Biological Sciences Research Council and it is part of the University of Edinburgh’s Royal (Dick) School of Veterinary Studies. More information can be found at https://www.ed.ac.uk/roslin/
Biomathematics and Statistics Scotland (BioSS)
is recognised internationally for work at the interface between the quantitative sciences and a wide span of applied sciences. BioSS specialises in methodological development and applications of statistics, mathematical modelling and bioinformatics to enhance scientific knowledge and increase the impact of research in agriculture and the rural economy, the environment, food and health. BioSS scientists maintain many collaborative research partnerships across the public and private sector. BioSS holds an Investor in People Gold Award and a Healthy Working Lives Silver Award. www.bioss.ac.uk
Moredun Research Institute and Biomathematics and Statistics Scotland are members of SEFARI
(Scottish Environment, Food and Agriculture Research Institutes), a consortium of six globally renowned research institutes. As SEFARI, these institutes deliver the Scottish Government funded Strategic Research Programme, which addresses key mid to longer-term challenges for Scotland’s environment, agriculture, land use, food and rural communities. https://sefari.scot/
For further information please contact:
Moredun Research Institute
Tel: 0131 445 5111