Scientists have looked at why humans infected with E. coli are more likely to suffer serious symptoms after studying toxins produced by the bacteria.

The team found that a toxin produced by naturally-occurring E. coli helps the bacteria colonize the intestinal tract of cattle and increases the transmission of the bacteria to other animals in the herd.

Scientists at the Moredun Research Institute, Roslin Institute (University of Edinburgh), Biomathematics and Statistics Scotland and partners showed that rapid and high levels of toxin expression also means infected people are likely to have more serious symptoms.

The study was funded by the Food Standards Agency and Food Standards Scotland and published in the journal PLOS Pathogens.

The key role of Shiga toxin type

Enterohaemorrhagic E. coli (EHEC) O157 is a subset of E. coli present in the gastrointestinal tract of cattle but doesn’t cause disease in these animals. However, EHEC O157 in the feces of infected cattle can be passed to humans through exposure to contaminated water, meat or vegetables.

EHEC produces Shiga toxins of various sub-types. These toxins can cause a variety of diseases from diarrhea with or without blood to more severe and potentially fatal kidney disease. The most dangerous toxin subtype is subtype 2a (Stx2a).

In the United Kingdom, phage type (PT) 21/28 O157 strains are the predominant cause of life-threatening EHEC infections and this phage-type commonly encodes Stx2a and Stx2c toxin types.

“Our study shows for the first time that Stx2a toxin plays a key role in allowing E. coli O157 to colonize the cattle gut, increasing the ability of Stx2a positive bacteria to transmit between animals and shed at high levels into the environment,” said Dr. Tom McNeilly, from the Moredun Research Institute.

“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.”

In a series of controlled cattle trials, researchers showed that calves orally dosed with a PT21/28 strain shed at significantly higher levels than those dosed with a PT32 strain.

The hypothesis that Stx2a is important for super-shedding and calf-to-calf transmission was tested by comparing the excretion and transmission dynamics of E. coli O157 strains with and without Stx2a.

Longer survival and higher levels

The study investigated the role of Stx2a in the colonization of the cattle gut and showed that it is critical in increasing transmission of EHEC O157 between cattle due to two factors.

First, Stx2a is produced quicker by the bacteria than other Shiga toxins and secondly, Stx2a promotes the persistence of the bacteria on cells that line the gastrointestinal tract of cattle by reducing their turnover rate.

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. So it increases the chance that bacteria can be passed to other cattle in the herd as well as to humans.

Professor David Gally of the Roslin Institute said the study explains the Stx2a subtype is common in E. coli O157 strains as it can be produced more rapidly compared to 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 colonize more easily, persist in the gut and can be excreted at high levels to go onto infect other animals and possibly humans.”

Moredun Research Institute, Roslin Technologies, Scotland’s Rural College and Roslin Institute at the University of Edinburgh are also funding commercial development of an E. coli O157: H7 vaccine for cattle.

The experimental vaccine has been developed to limit E. coli O157: H7 shedding from, and transmission between, cattle.

Roslin Technologies will perform a two-step validation trial from May to September 2020 in Nebraska. Field trials will examine super-shedding in cattle, which is the passing of large volumes of bacteria in feces, to see if the vaccine prevents shedding of the bacteria and is viable for commercial use.

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