A researcher in search of treatments for potentially fatal E. coli infections says the impossible is now plausible because of stem cell technology and organoids of intestinal tissues.

Antibiotics are frequently not recommended for patients infected with E. coli bacteria, making new treatment options especially important.

Professor Alison Weiss of the University of Cincinnati College of Medicine credits other scientists’ work as laying the foundation for her research, which is being partially funded by a four-year grant totaling $1.6 million from the National Institute of Allergy and Infectious Diseases (NIAID), which is part of the U.S. National Institutes of Health.

Those other researchers have used embryonic stem cells to develop the intestinal tissue that her laboratory will now use to test potential treatments for so-called hamburger E. coli. Weiss is working specifically on E. coli O157:H7, which came to the forefront of public attention during the deadly 1993 outbreak traced to undercooked hamburgers from Jack in the Box restaurants.

“What is interesting is in the cattle that carry the disease, the organisms just live right at their anal junction,” Weiss said in a university announcement this week. “It doesn’t bother the cattle systematically so we can’t identify them as sick …”

When cattle defecate, their feces become contaminated with the E. coli bacteria and that’s wher the problems begin for people. 

“For humans, the organisms grow in our small intestine and colon and those are very vital parts of our body that are attacked by the bacteria wheras a non-essential part of animal’s body is attacked. We had no way of looking at what the bacteria do until we got these human intestinal organoids.”

Organoids, according to the Harvard Stem Cell Institute, are tiny, self-organized, three-dimensional tissue cultures derived from stem cells. The institute reports that researchers have been able to produce organoids that resemble the brain, kidney, lung, intestines, stomach and liver.

Weiss, who is in the Department of Molecular Genetics, Biochemistry and Microbiology at Cincinnati University’s medical college, says that although E. coli O157:H7 is associated with hamburger, it is carried asymptotically by many creatures. From meat in slaughter plants to fresh produce, a wide variety of foods can become contaminated with the pathogenic bacteria because there are so many variables and vectors involved.

Any food or beverage that has even a tiny amount of microscopic fecal matter present can cause serious infections in humans. Vegetables and fruits can pick up E. coli if growing fields have been subject to wildlife incursions or irrigated with contaminated water. Weiss said the bacteria also can be introduced during harvesting and processing of fresh produce.

A case in point, Weiss said in the university announcement, is the largest E. coli outbreak of 2018 in the United States that was linked to romaine lettuce. The outbreak sickened at least 210 people in 36 states. Five people died and at least 96 were hospitalized. Federal investigators reported the most likely source of the E. coli O157:H7 was irrigation water from an open canal adjacent to a cattle feedlot that can handle more than 100,000 head.

Shiga toxin producing E. coli (STEC), including 0157:H7, are a a significant cause of diarrheal disease, causing about 265,000 illnesses in the United States annually. The infections often lead to bloody diarrhea, which is particularly dangerous for young children. Shiga toxin can result in hemolytic uremic syndrome, a condition caused by the abnormal destruction of red blood cells resulting in those damaged red blood cells clogging the kidneys leading to their failure and possibly death, according to Weiss.

In 2017, Weiss and Suman Pradhan, a research associate in the Weiss Laboratory, published “Intestinal Organoids Model Human Response to Infection by Commensal and Shiga Toxin Producing Escherichia coli” in the journal PLOS One.