Major cause of painful gastroenteritis under study at MCG

December 31, 2003

It may have made the B list for bioterrorism agents, but Campylobacter jejuni is on the A list when it comes to causes of painful gastroenteritis.

Eating inadequately washed and cooked chicken is the number-one cause of this bacterial infection that results in three to five days of bloody diarrhea, fever, intense abdominal pain and other flulike symptoms for 2.4 million Americans each year, said Dr. Stuart A. Thompson, microbiologist at the Medical College of Georgia.

Dr. Thompson recently received a $1.7 million grant from the National Institutes of Health to better understand just how this common infection makes people sick.

While Salmonella likely has greater name recognition, a report published in the January 2003 issue of Consumer Reports said Campylobacter was present in 42 percent of the chickens the magazine bought in stores nationwide while Salmonella was found in 12 percent; both bacteria, which cause similar symptoms, were found in 5 percent of the chickens.

Campylobacter has another unfortunate statistic: one out of 1,000 people who get it also develop Guillain-Barre¢ syndrome, an autoimmune response to a viral or bacterial infection that results in paralysis.

"This is one of the things that makes studying Campylobacter infections important," said Dr. Thompson, whose studies of the common bacteria include understanding exactly how it infects the body and developing a vaccine to prevent it.

"Most of these infections run their course and the patients are fine," he said. But weeks later, some people with certain, unidentified strains of the bacteria will develop Guillain-Barre¢ syndrome. "What appears to be happening in those patients with certain strains is there are sugars on the outside of the bacterium that resemble sugars on peripheral nerve cells. So the body detects this infection, mounts an immune response against it but inadvertently generates an autoimmune response against the body's own peripheral nerve cells," Dr. Thompson said.

And even though most strains cause short-term problems, the sheer number of infections results in a tremendous amount of illness along with the cost of medical treatment and lost days from work, he said. It was the massive, - albeit temporary - disabling potential of the bacterium that got it on the category B list of bioterrorism agents compiled by the Centers for Disease Control and Prevention and the National Institutes of Health.

Washing and cooking chicken well are the best ways to prevent Campylobacter infection. Hydration is standard treatment for those infected; some patients also take antibiotics to help shorten the duration of the illness, he said. But because animals and people are often treated with the same antibiotics, many strains of Campylobacter have become antibiotic-resistant, Dr. Thompson said. In fact, the same Consumer Reports survey showed that 90 percent of the Campylobacter they found - and 34 percent of the Salmonella - were treatment-resistant to common antibiotics.

So Dr. Thompson is looking for a way to immunize against the common bacteria by looking for proteins consistently found on the surface of all Campylobacter strains to use as a basis for a vaccine. "Proteins and sugars expressed by the bacteria are what the body's immune system is generating a response to," he said.

He is using MCG's Proteomics and Mass Spectrometry Core Facility, which looks at protein expression, to analyze a half-dozen strains. He is working toward broadening the protein search by collaborating with Dr. Irving Nachamkin, a public health microbiologist at the University of Pennsylvania, to access a wide range of strains taken from patients in Philadelphia.

Dr. Thompson believes he is on the right track looking for a vaccine. "You can develop immunity to Campylobacter," he said. As an example, children in Third World countries such as Thailand often get infected over and over again and, by the time they reach school-age, develop immunity to all local strains.

He also wants to know how the all-too-common infection makes people sick because, even though a textbook that bears its name already sits on his desk, there are still many unanswered questions that could lead to better treatment. "We are maybe 100 pieces into a 1,000-piece puzzle, so you can't see the whole picture," he said. "Diseases such as cholera, you can trace to the effects of cholera toxin. If you get rid of cholera toxin, it really doesn't make you sick. A lot of bacteria make strong toxins, including some kinds of E. coli. But Campylobacter is not like that. It does not have one major protein that, if you knock it out, you don't get sick any more. It's an inflammatory disease that we know a little bit about."

Body temperature, which is a cue for regulating some proteins, is one factor he's exploring. Chickens - which are the main hosts for Campylobacter yet are unaffected by the infection - have a higher internal temperature than people. "We are in the process of identifying proteins that are turned on in chickens and turned off in people and vice versa," Dr. Thompson said.

Another aspect of his work is the durable, dangerous Campylobacter fetus, a bacterium of the same genus but fairly distinct from Campylobacter jejuni. Healthy people typically are not affected by these bacteria, but people with AIDS and cancer, whose immune systems are compromised by disease or treatment, are easy targets. Infection can result from eating improperly handled or cooked beef; in fact, infection can cause spontaneous abortion in humans and cattle.

This bacterium also caught Dr. Thompson's attention because it has a crystal-like protein shield on its surface that enables it to escape the immune system, pass through the bloodstream and cause infections throughout the body. "We want to know how that structure is assembled on the cells. Specifically we are looking at how proteins that start inside the cells can be transported and assembled in this shield on the outside of the cell," he said.

In addition to the NIH grant Dr. Thompson just received to pursue his studies of the role of temperature-regulated proteins in making people sick, he also has NIH support for his campylobacter fetus studies. Also, the MCG Office of Technology Transfer and Economic Development recently applied for a patent on developing a Campylobacter vaccine.

Medical College of Georgia at Augusta University

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