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New protein targets for fighting stomach bacterium H. pylori


The first comprehensive study of proteins secreted by a stomach bacterium has yielded potential new targets for developing treatments against this common pathogen. Helicobacter pylori, which infects two-thirds of the world's population, is a leading cause of ulcers. Three antibodies recognized by the human immune system are among the proteins that could be targeted in therapies, such as vaccines, according to researchers.

Electron micrograph of Helicobacter pylori.

New therapies are needed in part because the organism lives between the cells that line the human digestive tract and the layer of mucus atop them. There, tucked securely behind the digestive tract's own protective mucus lining, the pathogen is sometimes difficult to reach with antibiotics.

The secreted proteins confirmed by a new study may prove "interesting candidates for innovative approaches to treat or prevent H. pylori infections," the researchers write in Infection and Immunity.

Although many infected people experience no symptoms, the bacteria cause more than 80 percent of all ulcers. Without treatment, a person remains infected for life and can develop long-term problems such as gastric cancer.

Studying and isolating secreted proteins in H. pylori has proven a challenge because cell cultures typically have foreign proteins that need to be isolated from those of the bacterium. Growing the bacteria in a protein-free medium, however, takes considerable amounts of time, prolonging research. Furthermore, H. pylori is prone to spontaneous lysis, or rupturing of the cell, which releases intracellular proteins into the medium.

A team led by Dirk Bumann of the Max-Planck-Institute for Infection Biology in Berlin, Germany, solved the problem by using cultures that discouraged lysis. To verify their results, the researchers performed gel electrophoresis on the secreted proteins.

Knowing that they were looking at secreted proteins only, the scientists next tried to identify the proteins using peptide mass fingerprinting. Out of 33 detected proteins, they identified 26. Among these 26 were eight 'hypothetical proteins' of unknown function, two of which had never been seen before.

Many of the known proteins are directly tied to H. pylori's ability to cause infection. Some are responsible for altering proteins in infected individuals, which allows the bacteria better access to their cells. Three proteins interact directly with a well-known toxin that helps the pathogen interfere with human cells.

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Bumann, D. et al. Proteome analysis of secreted proteins of the gastric pathogen Helicobacter pylori. Infect Immun 70, 3396-3403 (July 2002).

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