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Digestive Diseases News Winter 2011

NIDDK-supported Research Offers New Knowledge for Studying Effects of H. pylori Infection

Scientists studying Helicobacter pylori (H. pylori) may have uncovered new knowledge thanks to research funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Their research sheds light on the understanding of bacterial genes involved in repression of the gastric proton pump and of acid secretion.

H. pylori infection of the gastric mucosa causes gastritis, inhibits acid secretion, and may lead to the development of cancer. Acid secretion is mediated by the H,K-ATPase enzymatic proton pump in parietal cells that contains a catalytic α subunit (HKα). The same scientists had previously shown that H. pylori induces nuclear factor-kB (NF-kB) binding to and repression of HKα promoter activity in gastric epithelial cells. H. pylori eradication in humans increases HKα synthesis and restores acid secretion.

H. pylori strains containing a cag pathogenicity island (PAI) genetic locus cause severe gastric inflammation, ulceration, and increased risk of gastric cancer. Several cag PAI genes encode proteins that assemble into a type IV secretion system (T4SS) spanning the inner and outer bacterial membranes, which allows H. pylori adherence to host cells and enables transfer of virulence factors.

“This study identified the cag PAI as instrumental in H. pylori-induced HKα repression,” stated Adam Smolka, Ph.D., Medical University of South Carolina, and colleagues. “The study introduces a novel and potentially informative model for studying the molecular pathophysiology of human H. pylori infection, allowing for the first time controlled exposure of human gastric mucosa to different H. pylori strains and refined pharmacological interventions to dissect the affected cellular signaling pathways.”

The study showed that a small subset of H. pylori cag PAI genes play a role in repression of HKα transcription leading to inhibition of acid secretion. Researchers infected gastric epithelial cells and gastric biopsies with cagL, cagM, and cagE deficient strains of H. pylori and found that these strains failed to repress HKα promoter activity.

These results implicated gene products of H. pylori cag PAI genes cagL, cagM, and cagE in repression of HKα synthesis following acute infection and showed that repression is reflected in acid secretory inhibition. Researchers also showed that the H. pylori virulence factor CagA, which is injected into gastric cells upon infection, is involved in HKα repression.

As researchers understand how various H. pylori genes affect acid secretion, doctors may one day use this knowledge of the H. pylori genotype for therapeutic decision-making by identifying high-risk patients who warrant eradication therapy.

The National Digestive Diseases Information Clearinghouse, an information dissemination service of the NIDDK, has fact sheets and easy-to-read booklets about digestive disorders and H. pylori. For more information and to obtain copies, visit www.digestive.niddk.nih.gov.

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NIH Publication No. 11–4552
January 2011

Page last updated March 18, 2013


The National Digestive Diseases Information Clearinghouse is a service of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.

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