A new study highlights how a virulent strain of E. coli bypasses the gut’s defense mechanism, potentially opening new avenues for treating infections and chronic gut issues.
In an alarming new discovery, researchers from Genentech and Oregon Health & Science University (OHSU) have identified how a virulent strain of E. coli, known for causing bloody diarrhea, can circumvent the gut’s natural defense mechanism.
The study, published today in the journal Nature, sheds light on how this dangerous strain of E. coli injects a protein called NleL into gut cells, breaking down crucial enzymes — ROCK1 and ROCK2 — necessary for the infected cells to be expelled from the intestinal lining. This enables the bacteria to spread more easily within the body.
Typically, gut cells have robust mechanisms to expel infected cells quickly to halt infection. The intestinal lining, composed of tightly packed cells, acts as a first line of defense to keep harmful bacteria out of the bloodstream. If a cell gets infected, it sacrifices itself by pushing out into the intestines to be flushed away.
This process is thwarted by the protein NleL, giving the bacteria a free pass to multiply.
“This study shows that pathogenic bacteria can block infected cells from being pushed out,” senior author Isabella Rauch, an associate professor of molecular microbiology and immunology in the OHSU School of Medicine, said in a news release. “It’s a completely different strategy from what we’ve seen before. Some bacteria try to hide from being detected, but this one actually stops the cell’s escape route.”
Opening Path to New Treatments
Rauch’s expertise lies in understanding the complex interactions between the gut lining and microbial invaders. Her work is particularly significant for tackling both infectious diseases and chronic conditions like inflammatory bowel disease (IBD).
“We now know that the gut lining isn’t just a passive wall,” Rauch added. “These cells are really good at detecting infection early and responding to it before the immune system even kicks in.”
The study was a collaborative effort involving biochemical experts from Genentech and Rauch’s team at OHSU. Together, they demonstrated that the E. coli strain carrying the NleL protein is far more effective at infecting the gut by preventing the swift expulsion of infected cells.
“We were able to show that when the bacteria carry this certain protein, they infect the intestine much better,” added Rauch. “They prevent the infected cells from being kicked out rapidly, which gives them more time to multiply and infect more cells.”
This insight opens the door to novel treatments targeting bacterial mechanisms rather than killing bacteria outright, as conventional antibiotics do.
“By understanding how bacteria bypass our body’s defenses, scientists could design anti-virulence therapies that don’t rely on antibiotics,” Rauch added. “That’s really important, especially as antibiotic resistance continues to rise.”
A Global Health Concern
The implications of this study are far-reaching. This E. coli strain poses a high risk, particularly to young children who are more vulnerable to dehydration caused by diarrhea. Moreover, climate change and weakened food safety systems could exacerbate the prevalence of such infections.
“These kinds of bacteria are already a serious problem in places with poor sanitation,” Rauch added. “But with rising temperatures and cutbacks in food safety monitoring, they’re becoming a growing threat in developed countries too.”
The findings also offer valuable insights into gut disorders, including IBD and gastrointestinal cancers. Understanding the cell extrusion process could illuminate how the gut maintains its defense while offering clues about what goes wrong in diseases when the gut lining sheds too frequently.
“This cell ‘extrusion’ process happens in healthy guts all the time at a low level,” added Rauch. “But in IBD, it ramps up, and we don’t fully understand why. Similarly, we also see this in gastrointestinal cancers. This research gives us more insight into both sides of the equation, both how the body protects itself and how things go wrong.”