Helicobacter pylori are spiral shaped bacteria that live in the thick layer of mucus that covers the stomach lining. The bacteria are found everywhere in the world, but are especially prevalent in developing countries, where up to 80% of children and 90% of adults can have laboratory evidence of an H. pylori infection--usually without having any symptoms.
The vast majority of H. pylori in colonized hosts are free-living, but approximately 20% bind to gastric epithelial cells. This binding induces an immune response and alters the morphology and behavior of the epithelial cells due to injection of bacterial proteins into the cells. This interaction can lead to peptic ulcer disease, gastric adenocarcinoma, and non-Hodgkins lymphoma of the stomach.
"Ulcers are a breach in the gastric or duodenal mucosa and gastric adenocarcinoma is one type of cancer of the stomach," explains senior author Dr. Richard M. Peek, Jr. of the Vanderbilt University School of Medicine. "H. pylori alters acid production and can lead to increased acid outputs which causes peptic ulcer disease. The means through which H. pylori causes gastric cancer are more complex but likely involve alterations in gastric epithelial cell responses that are perturbed within the context of a chronic gastric inflammatory infiltrate, which can persist for decades."
A membrane-imbedded protein found in the stomach called decay-accelerating factor (DAF) has been shown to function as a receptor for several microbial pathogens. Peek and his colleagues were curious as to whether DAF was also involved in H. pylori adherence. To do this, the researchers measured the number of H. pylori that bound to cells that either expressed or did not express DAF. They found that the bacteria do indeed adhere to cells with DAF. They also discovered that H. pylori induce DAF expression in cultured gastric epithelial cells and that mice lacking DAF develop attenuated stomach inflammation.
"Our results indicate that H. pylori can co-opt a host protein as a receptor and that it can increase expression of this receptor in gastric epithelial cells," says Peek. "Further, absence of this receptor abolishes the inflammatory response that H. pylori induces in infected mice, suggesting that this receptor mediates H. pylori-induced injury in the stomach."
These findings suggest that drugs that interfere with DAF binding could be used to prevent or treat peptic ulcer disease or distal gastric adenocarcinoma. These new drugs will be a welcome alternative to the current treatment for H. pylori infections which typically involves taking 3 to 4 medications over a 10 to 14 day period.
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Journal of Biological Chemistry