Researchers at Washington University School of Medicine in St. Louis announced on June 17 that they have identified a common biological feature among major diarrhea-causing bacteria, potentially paving the way for a single vaccine to protect against multiple pathogens. The study focuses on enterotoxigenic E. coli and Shigella, which together cause hundreds of millions of infections each year and are leading causes of diarrheal death, particularly in children.
The research team, including collaborators from the University of Missouri and the International Centre for Diarrhoeal Disease Research in Bangladesh, found that these bacteria rely on three closely related enzymes to penetrate the gut's protective mucus layer and initiate infection. By analyzing samples from infected patients and volunteers exposed to these pathogens, scientists demonstrated that antibodies targeting one shared region across all three enzymes could neutralize their activity and block bacterial entry into intestinal tissue.
James M. Fleckenstein, MD, professor of medicine at WashU Medicine and co-senior author on the study, said, "For something so common and so deadly to young children, it's striking that we still don't have a vaccine for either of these pathogens. What's exciting here is that we've found a kind of Achilles' heel or weak point they share that we might be able to target to protect against both."
The study explains how gut pathogens must first break through a thick mucus barrier in the intestine before causing illness—a step facilitated by specific enzymes such as EatA (identified previously by Fleckenstein's lab), SepA (produced by Shigella), and Pic (found in other bacteria). The team isolated antibodies from Bangladeshi patients naturally infected with ETEC (enterotoxigenic E. coli) as well as from volunteers intentionally exposed during controlled studies; these antibodies blocked all three key enzymes.
Using cryo-electron microscopy at the University of Missouri, researchers pinpointed where effective antibodies attach—identifying a region conserved across all three enzymes. This discovery offers vaccine developers an exact molecular target likely capable of triggering broad protection if included in future vaccines.
Fleckenstein said, "These bacteria have evolved right alongside us, and they've gotten very good at breaching our defenses. If we can block that first step, we have a chance to stop these infections before they ever take hold." The team is now working toward developing such vaccines.
