While microbes are everywhere in the world, and in our bodies, many pose no threat to us. Others, however, can be very dangerous. There are many strains of Escherichia coli, some of which can live harmlessly in the gut. But there is also a dangerous E. coli strain that causes bloody diarrhea. Researchers have now shown that this pathogen can actually stymie defenses in the gut, causing the gut to retain nasty cells that would otherwise be removed. This helps the E. coli pathogen spread. The findings have been reported in Nature.
The body typically reacts with a strong defense when a gut infection is detected. The intestinal lining consists of tightly packed cells that form a tough barrier. If one of these cells is infected with a pathogen, it will destroy itself so that it is excised from the gut and the infection does not spread.
But the E. coli pathogen can make a protein called NleL and inject that bacterial protein into gut cells. This degrades enzymes called ROCK1 and ROCK2, which are necessary for the infected cells to be removed. Once those enzymes are disrupted, it’s hard for the infected cells to be eliminated.
"This study shows that pathogenic bacteria can block infected cells from being pushed out," said senior study author Isabella Rauch, Ph.D., an associate professor at the Oregon Health and Sciences University School of Medicine. "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."
This work highlighted that the lining of the gut is not a “passive wall,” but that the cells there can detect and respond well to infection, even “before the immune system even kicks in."
However, bacteria that make NleL are much better at infecting the intestine, added Rauch.
This research could help scientists create better treatments that disrupt these types of cellular mechanisms instead of destroying many bacteria 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."
Since this process of cell removal also ramps up in IBD for unknown reasons, this research could have implications for other disorders as well.
Sources: Oregon Health & Science University, Nature
