Scientists discover a shared weakness in deadly diarrheal pathogens

Researchers at Washington University School of Medicine in St. Louis have uncovered a shared weakness in two major diarrheal pathogens. Their findings could pave the way for a single vaccine to protect against both enterotoxigenic Escherichia coli (ETEC) and Shigella. The study has been published in the Proceedings of the National Academy of Sciences. The team identified a family of mucin-degrading enzymes that help these bacteria penetrate the intestinal mucus barrier. Three closely related enzymes—EatA, SepA, and Pic—are produced by ETEC, Shigella, and other pathogens. These enzymes are targeted by cross-reactive antibodies that neutralise their activity.

Using cryo-electron microscopy, the researchers found a structurally conserved region across all three enzymes. This discovery provides a foundation for designing vaccine antigens capable of triggering broadly neutralising antibodies. Naturally acquired antibodies against EatA have already been linked to protection from diarrheal illness in children, confirming its potential as a vaccine target.

The study was a multidisciplinary effort, drawing on expertise in infectious diseases, structural biology, immunology, and clinical research. Funding came from the National Institute of Allergy and Infectious Diseases and the Department of Veterans Affairs.

ETEC has been tied to recent foodborne outbreaks in industrialised nations, including the US. Its growing resistance to antibiotics makes it a significant global public health concern. The team is now working to turn these molecular insights into practical vaccine candidates. Preclinical testing and animal model studies are underway to block the enzymatic breach of the mucus barrier. If successful, the vaccine could prevent infection at its earliest stage and reduce the global burden of diarrheal disease.