Tulane researcher targets bacteria’s protective shield in search for E. coli vaccine

A Tulane University researcher is investigating how a common cause of a disease that poses grave risks for children worldwide protects itself inside the human body. It is work that could reveal new targets for a vaccine capable of stopping multiple strains of the bacteria.

Jacob Bitoun, assistant professor of microbiology and immunology at Tulane School of Medicine, has received funding from the National Institutes of Health to study biofilms formed by enterotoxigenic Escherichia coli, or ETEC.

ETEC is a type of E. coli that spreads through contaminated food and water. Once inside the small intestine, the bacteria release toxins that disrupt the body's normal fluid balance, causing severe diarrheal disease.

The infection poses the greatest risk to young children in low- and middle-income countries, where clean water and adequate sanitation may be limited. Travelers, military personnel and others exposed to contaminated food or water are also vulnerable.

There is no licensed vaccine against ETEC, which is especially difficult to prevent because it is not a single, uniform target. Scientists have identified more than 100 different serotypes or variations.

"For children, repeated infections can have consequences beyond acute diarrhea," Bitoun said. "Severe or recurring disease has been linked to malnutrition, growth stunting and impaired cognitive development. These long-term effects contribute significantly to the global burden of disease."

Bitoun's research focuses on biofilms, protective communities that bacteria form around themselves.

"You can think of it as a slimy, glue-like coating that allows bacteria to stick to surfaces and to each other while creating a barrier against outside threats," Bitoun said.

Recent work by Bitoun's lab suggests that ETEC growing in biofilms may withstand acidic conditions better, attach more effectively to intestinal tissue and cause more severe disease than bacteria that remain free-floating. The biofilm also may make it harder for the immune system and other natural defenses to eliminate infection.

"Biofilms appear to enhance survival under stressful conditions," Bitoun said.

The new study will examine whether ETEC produces distinctive molecules on its surface when growing within a biofilm. These molecules, known as antigens, can be recognized by the immune system and could potentially be used as vaccine targets.

Current ETEC vaccine research has largely focused on the structures the bacteria use to attach to the intestine. But those structures can differ considerably among strains, making it difficult to develop a vaccine that offers broad protection.

Bitoun and his team will grow ETEC under conditions that encourage biofilms to form and compare those bacteria with free-floating ETEC. By studying differences in the genes and proteins they produce, researchers hope to identify surface molecules that appear specifically - or become more prominent - when the bacteria are living in a biofilm.

The most promising targets would be found across multiple ETEC strains and would play an important role in helping the bacteria colonize the intestine or survive during an infection.

"If biofilm-associated antigens are shared by many strains, they could provide vaccine targets that are less variable than traditional colonization factors," Bitoun said.

A vaccine built around those shared targets could teach the immune system to recognize and block a wider range of ETEC strains, addressing one of the biggest challenges in developing an effective vaccine.

For Bitoun, a successful project would identify one or more biofilm-related antigens that are common across strains, essential to the bacterium's survival and able to produce a protective immune response in preclinical studies. Those findings, he said, could then lay the groundwork for additional testing and, ultimately, the development of a broadly protective ETEC vaccine.