June 25, 2002
Researcher asks: What makes E. coli go bad?
FARGO, N.D. - Lisa Nolan wants to know why some E. coli bacteria cause disease while most others don't.

Her research has identified a gene that's common among harmful forms of E. coli, but not among harmless strains. This finding could lead to an animal vaccine against E. coli that reduces human exposure to antibiotic-resistant bacteria and helps the agriculture industry reduce losses of poultry and livestock raised for food production.

Nolan, an associate professor in the Department of Veterinary and Microbiological Sciences at North Dakota State University (NDSU) in Fargo, is a doctor of veterinary medicine with a Ph.D. in medical microbiology. Her research, funded by a three-year, $142,000 grant from the National Institutes of Health (NIH), studies E. coli in poultry to learn more about how it impacts human health.

"We look at bacterial diseases in animals and try to understand how these bacteria cause disease in an effort to develop control points," Nolan says. "With the E. coli that cause disease in birds, we've identified a single factor that we think separates the good guys from the bad. We think we can use that as the basis of a vaccine."

Nolan's research team found that the E. coli which cause disease in birds overwhelmingly possess a gene called the increased serum survival gene or iss. This gene enables disease-causing strains of E. coli to overcome body defenses, allowing them to multiply and spread in the host.

"We're looking at why this gene is associated with 80 percent of disease-causing E. coli," she says.

Present in animal feces, certain strains of E. coli bacteria cause food poisoning in humans that can sometimes be fatal. Although undercooked hamburger is a common source of E. coli, it can also be spread through improperly treated drinking water or non-Pasteurized fruit juice. Typical symptoms of E. coli poisoning are diarrhea, cramps, fever, chills and vomiting. The elderly and very young are most susceptible to severe forms of this disease, which can result in kidney failure.

E. coli bacteria also pose a major problem for production animals in the agriculture industry. In birds, it frequently attacks the respiratory system. An E. coli outbreak in a large-scale chicken operation can cost millions of dollars. Also, calf scours caused by E. coli negatively impacts the cattle industry, each year killing thousands of newborn calves.

"Many times, infectious diseases in animals impinge on human health or the human pocketbook," Nolan says. "There are many diseases that can be passed from animals to human beings. A number of these diseases affect the safety of our food supply, so animal and human health is closely linked."

Working with Nolan are post-doctoral fellow Shelley Horne, research specialist Cathy Giddings, students Samantha Pfaff-McDonough, Steve Foley, Aaron Lynne, Jerod Skyberg, Tim Johnson and Jessica Ebert. They've found that the iss gene is located on plasmid DNA that can move between different bacteria, including other E. coli. A plasmid is a piece of DNA smaller than the chromosome that can contain important genes.

"In addition to containing the gene that we think is so important, this plasmid also contains several other known disease-causing genes," Nolan says. "And it contains the genes encoding resistance to some common antibiotics like tetracycline and ampicillin.

"Right now, our working hypothesis is that the use of these antibiotics in an animal production environment, such as a chicken house, might select for the bad bacteria. In other words, the antibiotic may select for the E. coli containing this plasmid," she says.

The agriculture industry has been criticized for using low doses of antibiotics to promote growth in production animals and for overusing antibiotics to treat disease.

"There's been a lot of criticism of these practices, but nobody has said why it may be beneficial not to use them," Nolan says. "What I think we're going to be able to do is say, 'Look, you're doing more harm to your operation than good.' Maybe this is a way to curb the inappropriate use of antibiotics."

Nolan explains that by using antibiotics to promote growth, livestock producers might be selecting for the bacteria containing genes that cause disease.

"Down the road, it's possible that these resistant bacteria can enter the food chain and reach human beings," she says. "This is the place where our work impinges on human health. Any intervention that we can do to control these infectious diseases of animals without antibiotics is a real plus. If we can control with vaccines or better management practices, we're all much better off."

Download a high-resolution photo of Lisa Nolan.

Contact information:
Lisa Nolan, associate professor, NDSU Department of Veterinary and Microbiological Sciences, at (701) 231-8530 or Lisa.Nolan@ndsu.nodak.edu

David Wahlberg, NDSU director of university news, at (701) 231-8325 or David.Wahlberg@ndsu.nodak.edu

Patrick Miller, public information professional, North Dakota Biomedical Research Infrastructure Network, (701) 777-6377 or pmiller@medicine.nodak.edu