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May 20, 2002

Researchers shed light on bacterial infection linked to ulcers and stomach cancer

By Linley Erin Hall

About 40 percent of the U.S. population is infected with a bacterium that can cause stomach inflammation and ulcers and increases the risk of stomach cancer. Although the bacterium, called Helicobacter pylori, was discovered in the 1980s, scientists are just now beginning to understand how it causes infections in the stomach lining.

H. pylori moves around using long protein "tails" called flagella.
Karen Ottemann, assistant professor of environmental toxicology, is studying H. pylori's ability to move around and the role this motility plays in infections. Her latest findings, published in the April issue of the journal Infection and Immunity, indicate that for H. pylori to start and maintain an infection, it needs to be able to swim.

"It's surprising that motility is used both to start the infection and probably to keep it going," Ottemann said.

Ottemann uses H. pylori as a model to understand the role of motility in host-parasite interactions generally. The molecular machinery involved in movement represents a potential target for new antibiotics, but no one really knows how bacteria use motility to infect humans and other mammals, she said.

Bacteria such as H. pylori move around in their animal hosts, but why they move, whether toward food, away from the host's immune cells, or toward or away from other molecules, is still an open question. H. pylori does not grow in the highly acidic stomach environment, so it may need to move quickly to the less acidic mucus layer that coats the stomach lining to achieve infection. Being able to swim in the mucus layer may also thwart the body's defense systems so that the bacterium causes a more persistent infection.

Infection with H. pylori usually occurs in early childhood, but symptoms do not become apparent until adulthood, if ever. Researchers believe that the bacteria are transmitted by ingestion of contaminated food or water or oral contact with an infected person. The infection process remains poorly understood, but Ottemann's research on the role of motility is shedding light on this mystery.

H. pylori moves around using long protein "tails" called flagella. Other researchers showed previously that H. pylori without flagella caused mild infections in mice. Ottemann and graduate student Andrew Lowenthal examined whether lack of motility or some other consequence of the lack of flagella reduced the bacteria's potency.

Ottemann and Lowenthal introduced mutations into the gene for a protein essential to H. pylori movement, so that the bacteria possessed flagella but could not move. The researchers then compared the mutant bacteria's ability to infect mice with that of normal H. pylori. Some mice exposed to the nonmotile bacterium did not become infected at all, and the ones that did contained fewer bacteria than mice infected with normal H. pylori. Furthermore, much higher doses of the mutant bacteria were required to establish an infection at all--more than one million mutants compared to only 150 normal bacteria. Thus, the bacteria need to be able to swim in order to start and maintain an infection, Ottemann said.

In the next phase of her research, Ottemann will create H. pylori in which the genes that produce proteins necessary for motility can be turned off after an infection has started. She hopes to show that by shutting down these genes she can halt an already established infection. If true, a compound that stops H. pylori from swimming could be a powerful drug.

Many people treat H. pylori-induced stomach inflammation with over-the-counter acid reducers until a painful ulcer sends them to a physician. After a breath test or stomach biopsy confirms H. pylori infection, the bacteria are usually wiped out by a course of antibiotics. But antibiotic-resistant strains of the bacterium are appearing.

Many other bacteria, including Campylobacter jejuni, the leading cause of diarrhea in the United States, also use flagella to move around. Ottemann's work on motility may be laying the foundation for a whole new class of antibiotics, and is shedding new light on host-parasite interactions.

"It's amazing how hosts and parasites interact," Ottemann said. "A tiny organism can mess up a large, complex one so easily."


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