Assistant Professor Melha Mellata, and members of her research team, graduate student Graham Redweik, center, and postdoc Zach Stromberg, have identified a mouse model that is not resistant to E. coli, paving the way for research into vaccines that could combat E. coli infections in humans. Photo by Whitney Sager.

Rodent model tested to study effects, treatment of E. coli

To understand human diseases and test the effectiveness of vaccines, mice often are used. However, when it comes to researching ways to fight harmful strains of Escherichia coli (E. coli) in the gut, a good mouse model that is not resistant to the bacteria has not been found, until now.

Assistant Professor Melha Mellata and her team of researchers from Iowa State University, in collaboration with Michael Wannemuehler, professor and chair of Iowa State’s Department of Vet Microbiology & Preventative Medicine, have discovered that mice with a limited number of normal bacteria in the gut can be infected with enterohemorrhagic E. coli (EHEC) for research purposes. Their findings are published online in the Disease Models & Mechanisms international biomedical research journal.

A foodborne pathogen, EHEC causes intestinal disease in humans. Mellata said children, the elderly, and individuals with compromised immune systems are particularly susceptible to complications caused by this strain of bacteria.

The problem when individuals contract EHEC, mainly from food, is there are no approved therapies to combat the bacterium. Graham Redweik, graduate student and member of Mellata’s research team, said some antibiotics can even make the infection worse. Hence the need for a mouse model to test the effectiveness of vaccines to combat EHEC infections.

Zach Stromberg, a postdoc in Mellata’s lab, began working on this project about two-and-one-half years ago. With a background in bacterial infections, Stromberg began testing various strains of the human disease to see how the mice reacted.

“Current models use antibiotics, which introduces a confounding factor when studying this bacterium. In contrast, our system is antibiotic-free,” Stromberg said.

Mice typically used for research purposes have thousands of bacteria in their digestive system. These mice often are resistant to E. coli, making them unfit for modeling the effects E. coli could have in humans. Wannemuehler provided Mellata and her team a special type of mice – known as altered Schaedler flora (ASF) mice – from Iowa State’s Veterinary Medicine College that only have eight bacteria in their gut. The purpose of the research would be to see if the ASF mice showed any E. coli resistance.

In contrast to current mouse models, EHEC was maintained in the ASF mouse gut for the entirety of the study. Furthermore, using special imaging to check for inflammation in the mice, it was determined these mice could exhibit signs of EHEC infection seen in humans.

Now that a useful mouse model has been identified, Mellata and her team have begun working to determine if any vaccines can combat EHEC in infected humans.

During a time of increasing numbers of food recall announcements due to contamination, this discovery has a potential to combat foodborne illnesses caused by E. coli.

“It’s important to have a good model to use for the questions we’re trying to answer, whether that be for this or any other projects,” Redweik said.

“More and more new bacteria contaminations are breaking out in food products. We need to be able to study foodborne E. coli and how to treat them,” Mellata added. “We need a good model to begin the steps to develop treatment for E. coli infections that are safe for human use.”