Pathogenic bacteria can block gut’s natural defense to spread infection

When harmful bacteria that cause food poisoning, such as E. coli, invade through the digestive tract, gut cells usually fight back by pushing infected cells out of the body to stop the infection from spreading.

In a new study published today in Nature, scientists from Genentech, a member of the Roche Group, in collaboration with researchers from Oregon Health & Science University, discovered that a dangerous strain of E. coli - known for causing bloody diarrhea - can block gut this defense, allowing the bacteria to spread more easily.

The bacteria inject a special protein called NleL into gut cells, which breaks down key enzymes, known as ROCK1 and ROCK2, that are needed for infected cells to be expelled. Without this process, the infected cells can't leave quickly, allowing the bacteria to spread more easily.

Usually, when harmful bacteria invade the gut, the body fights back quickly. The first line of defense is the intestinal lining - made up of tightly packed cells that absorb nutrients and keep bacteria out of the bloodstream. If one of these cells gets infected, it sacrifices itself by pushing itself out of the gut lining and into the intestines to be flushed. This helps prevent the bacteria from spreading.

This study shows that pathogenic bacteria can block infected cells from being pushed out.

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."

Isabella Rauch, Ph.D., senior author of the study and associate professor of molecular microbiology and immunology, OHSU School of Medicine

Revealing new paths for treatment

Rauch has spent her career studying how barrier tissues, such as the gut lining, interact with microbes and protect the body without constantly triggering inflammation. Her work is especially relevant for both infectious diseases and chronic conditions like inflammatory bowel disease, or IBD.

"We now know that the gut lining isn't just a passive wall," she said. "These cells are really good at detecting infection early and responding to it before the immune system even kicks in."

The study was a collaboration between multiple scientists, including biochemical experts from Genentech who figured out how NleL works, and Rauch's lab, which used models of gut tissue to show the protein's effects in real cells.

"We were able to show that when the bacteria carry this certain protein, they infect the intestine much better," Rauch said. "They prevent the infected cells from being kicked out rapidly, which gives them more time to multiply and infect more cells."

This discovery could pave the way for new treatments that target how bacteria cause disease, rather than killing the bacteria outright, like antibiotics do.

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

The findings also carry global health implications. This type of E. coli can be especially dangerous for young children, whose bodies can't handle fluid loss as well. Scientists warn that climate change and weakened food safety systems could make these infections more common.

"These kinds of bacteria are already a serious problem in places with poor sanitation," Rauch said. "But with rising temperatures and cutbacks in food safety monitoring, they're becoming a growing threat in developed countries too."

Beyond infectious disease, the discovery could also shed light on gut disorders like IBD, where the gut lining sheds too many cells too often.

"This cell 'extrusion' process happens in healthy guts all the time at a low level," Rauch said. "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."

In addition to Rauch, OHSU co-authors include Marin Miner, B.S., Rachael Peterson, B.S., and William Scott, B.A. The lead author is Giovanni Luchetti, Ph.D., principal scientist at Genentech.