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Persistent stomach bug H. pylori uses sugar to trick immune system


Scientists have discovered a protein that plays a key role in one of the most common bacterial infections worldwide and that may be a candidate for a vaccine. The protein, called SabA, allows the bacterium H. pylori to use the body's immune system to its own advantage. Its presence may explain how the pathogen causes such a persistent infection.

Detail from figure showing how H. pylori adheres. View full

More than half of the world's population is infected by H. pylori, which is a leading cause of ulcers and a risk factor for stomach cancer. Especially prevalent in developing countries, infections typically start in infancy and can last for decades.

A team of researchers from Sweden, Estonia, and the United States reports in Science that the H. pylori pathogen uses SabA to microscopically 'grab' onto special sugars on stomach cells. Cells bring these sugars to their surfaces to attract immune cells. Their purpose, explains researcher Thomas Borén, is "to signal to the body that part of the tissue is in need of help." Because of SabA, however, the sugars actually make the infection worse.

Adhering closely to the stomach wall gives H. pylori improved access to nutrients, which leak through the membranes of infected cells. This also protects the bacteria from being flushed out by the stomach's natural mucus shedding.

The discovery of SabA may also explain why H. pylori infections seem to flare up occasionally and then subside. The sabA gene can turn on and off easily, allowing the bacteria to back off—literally—in case of an immune response. Although this causes the symptoms of infection to disappear, the bacteria aren't actually eliminated. Instead, they reside farther away from the stomach lining until the immune response relaxes, at which point they can attack again.

Researchers discovered SabA by creating a 'knock-out' mutant of H. pylori that was unable to establish an infection. To their surprise, they found that the mutant bacteria could bind to cells that were already infected, because these cells had the special sugars on their surfaces.

SabA is a promising vaccine target because it appears to be unique to H. pylori. "There is nothing even similar in any other bacteria," Borén notes. Vaccine specificity is especially important in the gastrointestinal tract, which contains numerous beneficial microbes.

Although H. pylori can be treated with antibiotics, treatment is not always successful because the bacteria live behind the stomach's layer of protective mucus. Many researchers view a vaccine as an ideal way of fighting infections globally, because widespread use of antibiotics creates undesirable resistance.

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Mahdavi, J. et al. Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation. Science 297, 573-578 (July 26, 2002).

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