Listeria Yields a Deadly Clue

Research shows how bacteria invade cells

THURSDAY, May 31, 2001 (HealthDayNews) -- By breaking the molecular code used by listeria bacteria to invade human cells, French scientists have created an animal model that opens a new frontier in the fight against the deadly germs that cause food poisoning and other diseases.

A single protein on listeria's surface is the key that enables the bacterium to enter human cells, and a single amino acid in a receptor protein on the surface of cells is the lock that controls the door to those cells, report researchers led by Pascale Cossart, a professor at the Pasteur Institute in Paris, in the June 1 issue of Science.

Because the lock opened by the bacterial protein is found on human cells, but not on cells of rats and mice, the French researchers created a strain of transgenic mice with a human version of the receptor.

"If you are ever going to block listeria disease, this is where you are going to do it," says B. Brett Finlay, professor of biotechnology at the University of British Columbia in Vancouver, Canada, and author of an accompanying commentary.

Listeria can contaminate raw vegetables and poorly preserved processed foods. About 2,500 cases of listeriosis occur in the United States each year. The death rate is above 20 percent, mostly among newborns, older adults and persons with weakened immune systems. The disease occurs when listeria from contaminated food moves from the stomach into the bloodstream, then into the central nervous system. Until now, the molecular events that allow the invasion have been a mystery.

The French researchers identified a protein they call internalin on the listeria surface membrane as the key. And they identified the lock as a specific variant of a receptor protein called E cadherin on the surface of intestinal cells. By checking each amino acid in the chain that makes up the receptor molecule, the researchers found that the receptor will react with internalin only if an amino acid called proline is in the 16th position.

Humans have proline in that position. Mice and rats have a different amino acid, glutamic acid, which does not interact with internalin and therefore prevents listeria infection. The transgenic mice created by the French researchers contain the human form of E cadherin and will be a great help in related research, Finlay says.

"Because we didn't know how listeria got across the gut barrier, in the mouse model we have been injecting listeria directly into the animal, bypassing the oral route," he says. "This gives us an animal model that enables us to look at orally acquired infections."

While similar animal models have been developed for viral disease research, this is the first one for a bacterial infection, and it opens the way for similar models for other bacterial infections, including gonorrhea and typhoid fever, Finlay says.

"If you are going to study a disease, the more relevant the animal model is to the human disease, the more confident you are about the study," he says.

And the lock-and-key molecular mechanism has another potential use: It could also be used to carry medications into human cells, the French researchers say.

What To Do

While the research unlocks a secret about bacterial infections, prevention still is the first line of defense.

The Food and Drug Administration (FDA) issued a consumer advisory in March saying that perishable pre-cooked or ready-to-eat foods should be consumed as quickly as possible to reduce the risk of listeria infection. Refrigerators should be cleaned regularly and kept at a temperature of 40 degrees, the FDA says. Pregnant women, older people and those with weakened immune systems should avoid certain soft cheeses, refrigerated pates or meat spreads, refrigerated smoked seafood, and hot dogs and luncheon meats that are not steaming hot, the FDA says.

For detailed information on listeriosis and how to avoid it, go to the Centers for Disease Control and Prevention or the U.S. Department of Agriculture's Food Safety and Inspection Service.

Check these previous HealthDay articles about listeriosis.

SOURCES: Interview with B. Brett Finlay, Ph.D., professor of biotechnology, University of British Columbia, Vancouver, Canada; FDA; June 1, 2001, Science
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