Foiling food-borne infection
A sunny day, a barbecue grill, plates full of favorite summertime foods—all the ingredients of a perfect cookout. But an uninvited guest can spoil the good times, especially if it’s the bacterium Campylobacter jejuni.
The bug, which frequently contaminates raw chicken, is the leading cause of bacterial diarrheal illness in the United States and causes fever, abdominal pain, nausea, headache and muscle aches in addition to the main symptom. More than 2 million cases are estimated to occur in this country every year, and while most people recover, about one in every 1,000 cases is fatal. Young children, older people and people with underlying illnesses such as cancer or HIV/AIDS are particularly vulnerable. In addition, infection with Campylobacter can lead to Guillain-Barré syndrome, a disease in which the body’s immune system attacks part of the nervous system, resulting in weakness or paralysis.
“This is an organism that certainly has been causing disease in humans for a long time, but only within the last 25 years or less have we come to appreciate how much disease it causes,” says Victor DiRita. Difficult to culture, Campylobacter was long overlooked when medical sleuths tried to pinpoint the culprits behind outbreaks of illness. “And because it had been missed, it hadn’t been well-studied, so that’s what got me interested,” DiRita says.
Although humans react violently to Campylobacter, chickens show no signs of illness when infected. This presents a challenge for chicken producers, who can’t easily tell which chickens harbor the bug.
The challenge for DiRita is two-fold: understanding why the colonization process in chicken leads to a completely different outcome than colonization in humans; then figuring out how to intervene to eliminate or reduce Campylobacter in the food supply.
Currently, antibiotics are used to contain Campylobacter in chickens, but Campylobacter is developing resistance to antibiotics, and consumers are pressing for antibiotic-free animal products, so “there’s a great deal of interest worldwide in developing cost-effective, new approaches,” DiRita says.
“In our lab, we’ve developed a number of methods and tools to study the organism in its natural host,” he says. “For example, we’re using genetic methods to help us identify factors in Campylobacter that are required for it to colonize chickens. Using that knowledge, we then want to develop either vaccines or inhibitors of those processes that will make it possible to stop or at least contain the infection.”
One such trait is a trick that only Campylobacter and a handful of other bacteria are capable of performing: decorating recently produced proteins with sugar molecules. Human cells routinely do this—the process (called glycosylation) is essential to proper protein function, which underlies practically everything the body does, from transporting oxygen to repairing tissues and organs to keeping the immune system working properly—and Campylobacter executes the process much as human cells do, with a few important exceptions.
“We discovered that protein glycosylation is essential for Campylobacter to colonize the chicken gastrointestinal tract and probably to do a lot of other things, like cause disease in humans,” DiRita says. “So the protein glycosylation system in Campylobacter has become, for us, a very specific target.”
Working with researchers in the drug discovery laboratory at U-M’s Center for Chemical Genomics, DiRita’s group will be searching for compounds that will inhibit protein glycoslyation in Campylobacter.
“Although the process is similar to what goes on in humans, the actual enzymes that do the glycosylation are quite specific to Campylobacter,” DiRita says. That means that drugs developed to squelch glycosylation in Campylobacter would affect bacterial processes, but not have harmful effects on humans.
Such a safe and effective solution to the Campylobacter problem would indeed be cause for celebration. Cookout, anyone?
