Researchers Uncover Burrowing Secrets of Ulcer Bacteria

Newswise — A researcher at the University of Virginia Health System and colleagues have uncovered the secret to the way that Helicobacter pylori infiltrate the stomach lining and cause ulcers.

Paul S. Hoffman, Ph.D., in the UVa Division of Infectious Diseases, has discovered that these bacteria, which are also a risk factor for developing often-lethal stomach cancers, have developed an ingenious way to colonize in the harsh, acidic environment of the stomach. Last year, UVa gastroenterologist Dr. Barry Marshall co-won the Nobel Prize for Medicine for his discovery of H. pylori, which colonize in almost half of the world's population.

They discovered that these bacteria can sense acid concentration and that they use natural gradients of acid, from high to low, to move to a place where they can exist and multiply. "They swim from the highly acidic lumen of the stomach down to the underlying epithelial cells where there is less acid," says Dr. Hoffman.

To do this, an acid-sensing receptor at one end of the bacteria must communicate information to the flagella, the whiplike tails at the other end that move the bacteria.

In the Journal of Bacteriology, Hoffman and colleagues write that their group identified the chemoreceptor (TlpB) that senses the pH of acid. They showed that a mutant bacterium that has lost pH sensing can no longer colonize in the stomachs of mice, the animal model often used to study the disease. The researchers reasoned that if they restored the functional gene for this chemoreceptor in the mutant bacteria, the bacteria would be able to sense acid, move to a less acidic location and colonize. This hypothesis proved true.

"Because pH sensing ability is essential for colonization and persistence in the stomach lining tissue, the TlpB pH receptor might represent a novel target for the development of treatments that can interfere with this behavior," Hoffman says. "H. pylori infections occur most often in developing countries that can't afford the cost of miracle drugs. Perhaps a narrow-spectrum drug designed to block the chemoreceptor would be less expensive to develop."

The citation: Croxen, M.A., G. Sisson, R. Melano, and P.S. Hoffman. 2006. The Helicobacter pylori chemotaxis receptor TlpB (HP0103) is required for pH taxis and for colonization of the gastric mucosa. Journal of Bacteriology. 188:2656-2665.