14 Jan 2005
Finding how the fowl-borne bacteria Campylobacter jejuni makes at least a million Americans miserable for a week each year is on the plates of two Medical College of Georgia microbiologists.
Raw and undercooked poultry and meat, raw milk and untreated water are sources for Campylobacter, the most common bacterial cause of diarrhea in the United States, according the U.S. Public Health Service.
But finding how these bacteria that happily co-exist with chickens and turkeys burrow their way into intestinal cells to eat and make people sick in the process should provide direction on how to stop them, say Drs. Stuart A. Thompson and Christopher M. Burns.
“The basic problem with Campylobacter is that we don’t know how it causes disease,” says Dr. Thompson, who recently received his third National Institutes of Health grant to answer this question and develop a vaccine. “To understand how to treat a bacterium, you have to understand how it causes disease.”
He and Dr. Burns, co-principal investigator on the latest grant, are learning that the mindless microorganism is an incredibly skilled survivor.
“What we are working on is one of the basic mechanisms of any bacterial disease: that bacteria regulate their own genes in order to cause whatever disease process they cause,” says Dr. Thompson. “Bacteria exploit their hosts to live.” And the human body is ripe for picking. “Think about it, inside human cells are tons of goodies, all kinds of sugars and other elements. If bacteria can get there, cause the cells and tissue to become inflamed, cells starts releasing all these nutrients and the bacteria have things to eat. In fact, bacteria don’t want to kill a host because then they run out of nutrients.”
All this exploitation requires being responsive to the environment. “Organisms can sense where they are in people and respond by changing their gene expression so they are making the right proteins for the environment they happen to be in,” says Dr. Burns.
The researchers are exploring this exploitation to learn how gene regulation changes. Dr. Burns is using microarray technology to look at gene expression in Campylobacter, which has one of the smallest genomes of any free-living bacteria, a fact that should simplify the search somewhat. Dr. Thompson is using proteomics to look at protein expression patterns of genes. “Mostly it’s trying to work out regulatory pathways,” he says.
As an example, temperature, which can regulate some protein expression, may play a role in why Campylobacter live harmlessly in normally warm chickens and makes cooler humans sick. In looking at proteins turned off and on in chickens and people, Dr. Thompson zeroed in on one called CJ1461 that is turned on in people. The “wild hope” he had that this unusual protein was involved in gene regulation appears to a reality.
When the researchers disabled the protein, gene regulation went haywire, Dr. Thompson says. “So we have hit on something that affects a large number of different processes in the cells. The genome of Campylobacter had been sequenced so CJ1461 was known, but there was only an educated guess as to what it did. What it appears to be is a DNA methylase, which means it adds methyl groups to DNA to somehow change gene regulation,” says Dr. Thompson.
“One of the things that we are finding is that CJ1461 controls how the cell can swim,” says Dr. Thompson. “Campylobacter have little tails called flagella so they can swim, and their ability to swim is critical for getting where they need to go.”
One place Campylobacter want to go is to the intestinal wall where they can get inside cells, eat and hide from the immune system. But they have to work hard to get there, including swimming through the thick mucus constantly being shed by the gut. CJ1461 is involved in the gene regulation necessary to produce much-needed tails for the task. The protein also appears to affect the bacteria’s ability to take up iron, which is scarce and necessary for life.
CJ1461 also seems to work as a lifesaver for Campylobacter by helping the bacteria survive oxygen radicals released by the immune system when it sees the invaders. These oxygen radicals also prompt the intestinal inflammatory response that makes people sick.
Symptoms include diarrhea, cramping, abdominal pain and fever; in the worst-case scenarios, which are fortunately rare, people develop Guillain-Barre’ syndrome, a paralysis-inducing autoimmune response to a bacterial or viral infection.
Drs. Burns and Thompson hope their studies will help identify targets for better treatments for the disease and ultimately a vaccine to prevent it.
In the meantime, they encourage consumers to cook poultry products thoroughly and carefully wash their hands, pots, utensils, counters and anything else that comes in contact with raw poultry.