How Common E. Coli Strain Uses ‘Double-Attack’ to Destroy Gut From Within

MELBOURNE, Australia — Over a million children die each year from severe diarrhea, often caused by a dangerous strain of E. coli. Now, researchers at La Trobe University in Australia have mapped the 3D structure of one of E. coli’s deadliest toxins, revealing how it slips past our body’s defenses to attack gut cells from within.

The study, published in the journal Gut Microbes, shows how this bacterial toxin, called EspC, invades human cells using a specialized “injection system” and then cuts essential proteins that hold cells together.

“This toxin is unusual because it uses two different systems to reach its target,” says lead researcher Begoña Heras from La Trobe University, in a statement. “This double-attack approach makes it especially good at damaging intestinal tissue and explains why these infections can become so severe so quickly.”

How This Harmful E. coli Causes Deadly Diarrhea in Children

This type of E. coli, called enteropathogenic E. coli or EPEC for short, remains a serious health problem in places with limited access to clean water. Unlike other harmful E. coli strains that produce Shiga toxins (like those responsible for recent spinach recalls), EPEC relies heavily on EspC to damage the gut lining.

“This is alarming as 1.3 million children under the age of five die each year from diarrheal illnesses due to the associated severe dehydration and loss of essential electrolytes,” says Heras.

The research team used X-ray crystallography to get a detailed look at the EspC toxin. They found that the toxin has several parts: a cutting tool (enzyme domain), a large central stalk with a spiral shape (β-helix), and additional sections that stick out from the main body.

Surprisingly, none of the projecting sections were needed for the toxin to enter human cells. Instead, the spiral-shaped stalk, a common feature in many bacterial proteins, was what allowed the toxin to interact with the bacteria’s injection system. It sort of acted like a microscopic needle used to inject proteins directly into human cells.

How the Toxin Tears Apart Intestinal Cells from Within

Once inside intestinal cells, the toxin’s cutting tool damages structural proteins that normally hold cells in their proper shape. When these proteins are cut, intestinal cells round up and pull away from each other, breaking down the gut barrier and causing watery diarrhea.

In lab experiments using human cells, the researchers discovered that removing one particular section (called SD3) from the toxin actually made it better at entering cells and causing damage. This section seems to act like a brake, preventing too much toxin from entering cells too quickly.

Working Toward New Treatments for a Deadly Disease

With antibiotic resistance on the rise, understanding the specific mechanisms that bacteria use to cause disease is even more important. The researchers compared EspC with similar toxins from other bacteria. While these toxins look similar in structure, they use different methods to enter cells.

This helps explain why EPEC infections can progress so quickly: the toxin delivery system bypasses many normal cellular defenses. By understanding these differences, scientists hope to develop new approaches to block the toxin from entering cells or stop its activity once inside.

Rather than relying solely on antibiotics that kill both harmful and beneficial gut bacteria, future therapies could specifically block the EspC toxin. This would prevent the cascade of cell damage that leads to severe diarrhea while preserving the gut’s healthy bacterial balance, an approach urgently needed in an era of rising antibiotic resistance.