Researchers are studying the role of Shiga toxin in the immune system

Food poisoning by E. coli is one of the worst food poisons, causing bloody diarrhea and kidney damage. But all meats may have just an unintended side effect, researchers from UConn Health said in a November 27 issue of Psychology of science. Their findings could lead to more effective treatments for this potentially fatal disease.

Escherichia coli is a diverse group of bacteria that often live in the gut of animals. Many strains of E. coli will never make us sick; other types can cause diarrhea in the passenger. But swallowing even a few E. coli-type cells that produce Shiga toxin can make us very sick. Shiga toxins damage blood vessels in the abdomen, causing bloody diarrhea. If Shiga toxin gets into the bloodstream, it can cause kidney failure.

This is especially common in children; about 15% of children with toxin – producing E. coli infections get kidney disease, and some may suffer long – term kidney damage. “

Sivapriya Vanaja, Health Immunologist, University of Connecticut

A group of E. coli that make up Shiga toxin called enterohemorrhagic E. coli, or EHEC, is particularly common in the United States. When you hear that a batch of lettu romaine has been recalled as a result of a dangerous outbreak of food poisoning, it is almost certainly the result of EHEC.

EHECs usually live in cattle without making them sick. It used to be very common for EHEC outbreaks to come from unhealthily prepared ground meat, but strict regulations on slaughterhouses have made this less common. EHEC is now more likely to appear on vegetables grown in fields adjacent to cattle or manure.

But no matter where it comes from, once bacteria get EHEC inside a person, it is difficult to treat the disease. Antibiotics tend to make it worse – when the bacteria feel themselves dying, they make more Shiga toxin. And EHEC is very good at blocking the part of the immune system that normally responds early to this type of infection, allowing it to grow undetected in human gut.

In a study led by Morena Havira, a postdoctoral fellow in the Vanaja lab, the team wanted to find out how EHEC destroys the immune system. The body normally responds to early stages of E. coli disease by activating an enzyme that sends an alarm device inside cells. The cell explodes open to release a cloud of warning molecules that call other parts of the immune system to come and fight the bacteria.

But EHEC is scouring that early response. To find out how it does that, Vanaja and her colleagues decided to see which individual gene in EHEC was responsible. They took many different types of EHEC from a bacterial mutant library, and brought immune cells with them.

The team found that cells with EHEC that lost the gene for Shiga toxin had a higher immune response compared to normal EHEC.

“It was a surprise. Shiga’s toxin has been well studied for its toxic activity; it was not known to have another action,” Dr. Vanaja says. So Shiga toxin may have a positive connection to the immune system with all the resulting bloody drama. Inspired by this interesting observation, they performed a series of detailed molecular studies, which showed that Shiga toxins block proteins from exploding the infectious cell and warn the body of infection.

Now that Vanaja and her colleagues are aware of the specific molecular action of Shiga toxin inhibition inside the immune cells, they are trying to figure out how, exactly, preventing it. Once they know that, they may be able to find drugs that prevent toxins from interfering with immune responses.