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Researchers Find New Way to Attack Stomach-Ulcer Bug

X-rays identify drug target for bacteria that affect millions of people worldwide (Dec. 10)

Researchers at the U.S. Department of Energy's SLAC National Accelerator Laboratory in Menlo Park, Calif., have found a potential new way to attack common stomach bacteria that cause ulcers and significantly increase the odds of developing stomach cancer.

The discovery — published online in Nature — was the culmination of 5 years of research into the bacterium Helicobacter pylori, which is so tough it can live in stomach acid. At least half the world’s population carries H. pylori, and hundreds of millions of people experience health problems as a result; current treatments require a complicated regimen of stomach-acid inhibitors and antibiotics.

“We were looking for a means to disrupt H. pylori’s own mechanism for protecting itself against stomach acid,” said principal investigator Dr. Hartmut Luecke. “We have deciphered the three-dimensional molecular structure of a very promising drug target.”

Luecke and his team focused on tiny channels that H. pylori bacteria use to allow the entry of urea from gastric juice in the stomach; the bacteria then turn this compound into ammonia, which neutralizes stomach acid. Blocking this protective system may lead to a new treatment for people with H. pylori infection, the researchers say.

Solving the structure of the protein to find the specific area to target wasn't easy, however. The channels are formed by the protein embedded in the bacterium’s cell membrane, and membrane proteins are notoriously difficult to crystallize, which is a prerequisite for using protein crystallography — the main technique for determining protein structures. This technique bounces X-rays off of the electrons in the crystallized protein to generate experimental data, which can be used to build a 3-D map showing how the protein’s atoms are arranged.

“You have to try all kinds of tricks, and these crystals fought us every step of the way,” Luecke said. “But now that we have the structure, we’ve reached the exciting part — the prospect of creating specific, safe, and effective ways to target this pathogen and wipe it out.”

Source: SLAC National Accelerator Laboratory; December 10, 2012.

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