UT researchers find treatment for food poisoning-related infections

Kevin Lokuwaduge

A breast cancer drug may be the key to treating some food poisoning-related infections, according to a paper published June 26 by UT researchers.

Shiga toxin-producing E. coli infections are a major cause of food poisoning around the world. In the United States, these infections led the Centers for Disease Control and Prevention to recall products such as beef and lettuce earlier this year.

“(Shiga toxin-producing bacteria) is not just in developing countries,” said Somshuvra Mukhopadhyay, whose lab worked on the study. “It is very rampant in North America and Europe because a lot of the food products that get contaminated are routinely used in cooking over here.”

Until now, a treatment for the toxin has been unavailable, but researchers at UT have found a potential treatment for Shiga toxin-producing E. coli infections with the use of an FDA approved drug called Tamoxifen, which is most commonly used in the treatment of breast cancer.

“Even one (Shiga toxin-producing E. coli) is sufficient to cause a full-blown disease,” said Mukhopadhyay, an assistant professor of pharmacology and toxicology in the College of Pharmacy.

Andrey Selyunin, lead author of the research paper about the treatment, said the toxin within the E. coli comes from a bacterial virus rather than the bacteria itself.

“The main problem with these E. coli infections that have Shiga toxin is not that we can’t kill the bacteria,” said Selyunin, a research associate at the College of Pharmacy. “It’s that, while in the process of killing the bacteria, the toxin gets released.”

The toxin comes in two variants: Shiga toxin 1 and 2. Shiga toxin 2 is the one commonly found in food poisoning, said Steven Hutchens, lab manager for Mukhopadhyay’s Laboratory.

“What we know about both toxins is … that they stop protein synthesis which is lethal to the cell, but the routes that they use to get there are different,” Hutchens said.

Selyunin and Mukhopadhyay found a treatment for Shiga toxin-producing E. coli infections through an investigation into the way the toxin was entering human cells. By manipulating the pathway of cells, they made mutant versions of cells that were resistant to the Shiga toxin.

“We figured that because that field is pretty well studied, there’s got to be some drug that might induce these same effects,” Selyunin said. “We focused on specifically FDA approved (drugs).”

Typically, foreign pathogens get broken down in compartments of the cell called the lysosome. The Shiga toxin manages to escape this normal pathway. However, treatment of cells with Tamoxifen brings the toxin back into the normal degradation pathway.

The biggest advantage of finding an FDA approved drug is a quicker clinical trial, Mukhopadhyay said. The remaining work is to find the proper dosage required for treatment.

“The most important thing is that there was nothing known about how to attack Shiga toxin 2 toxicity, and now we have a better understanding of how we can tackle Shiga toxin-producing E. coli infections,” Hutchens said. “Food poisoning is an issue, and it can be potentially lethal.”