A new study published in Nature reveals how a dangerous strain of Escherichia coli, which is known for causing bloody diarrhea, can override the gut’s natural defense system, potentially increasing the severity and spread of infection. The study was conducted by researchers from Genentech (a member of the Roche Group) and Oregon Health and Science University (OHSU).

Under normal conditions, the intestinal lining responds to infection by pushing compromised cells out into the gut lumen, a process known as cell extrusion. This mechanism helps prevent bacteria from gaining a foothold. However, the strain of E. coli discussed in the study uses a virulence factor—the ubiquitin ligase NleL—to block cell extrusion.

NleL, a bacterial protein, targets and degrades key host enzymes ROCK1 and ROCK2, which are essential for cell extrusion. Without these enzymes, infected cells remain in the gut lining longer, giving the bacteria more time to replicate and spread. This strategy is different than others previously observed by researchers.

To uncover how NleL works, researchers used a combination of cell culture, mouse models, and proteomic analysis. They showed that NleL degrades ROCK1 and ROCK2 through a process called ubiquitination, which marks proteins for destruction. Infected mice lacking these enzymes were less able to clear the bacteria, confirming the role of ROCKs in gut defense.

Implications for Food Safety and Public Health

The findings have significant implications for food safety and public health. This strain of E. coli is particularly dangerous for young children, who are more vulnerable to dehydration and complications from gastrointestinal infections.

Moreover, as climate change and reduced investments in food safety defenses continue to favor bacterial survival and challenge global sanitation systems, infections by increasingly threatening foodborne pathogens may become more common—even in developed countries.

“These kinds of bacteria are already a serious problem in places with poor sanitation,” said Isabella Rauch, Ph.D., senior author on the study and Associate Professor of Molecular Microbiology and Immunology at OHSU. “But with rising temperatures and cutbacks in food safety monitoring, they’re becoming a growing threat in developed countries too.”

Beyond cases of foodborne illness, the study may also shed light on chronic gut disorders like inflammatory bowel disease (IBD), where excessive cell shedding is a hallmark. Understanding how extrusion is regulated could inform future treatments for both acute infectious and inflammatory conditions.

The researchers also used advanced imaging to track cell extrusion in real time and employed genetically engineered bacterial strains to isolate the effects of NleL. Their findings suggest that targeting bacterial virulence, rather than killing bacteria outright, could be a promising strategy for future therapies.

“By understanding how bacteria bypass our body’s defenses, scientists could design anti-virulence therapies that don’t rely on antibiotics,” Dr. Rauch said. “That’s really important, especially as antibiotic resistance continues to rise.”

The study was led by Giovanni Luchetti, Ph.D., principal scientist at Genentech, with contributions from Dr. Rauch’s lab at OHSU. Co-authors include Marin Miner, Rachael Peterson, and William Scott. The research was funded by the National Institute of Health’s National Institute of Allergy and Infectious Diseases (NIH’s NIAID).