# Pathogenesis of Helicobacter pylori infection

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2020 · —

## Abstract

Helicobacter pylori is a Gram-negative bacterium that colonizes the human stomach. H. pylori infection is
associated with an increased risk of cancer of the distal stomach, as well as peptic ulcer disease. The World
Health Organization has classified H. pylori as a type I carcinogen, and gastric cancer is the third leading
cause of cancer-related death worldwide. The long-term goals of this work are to understand the molecular
mechanisms that allow H. pylori to persistently colonize the human gastric mucosa, to understand the
molecular mechanisms by which H. pylori infection leads to the development of gastric cancer or peptic
ulceration, and to develop effective strategies for the prevention of these diseases. To achieve these long-term
goals, we seek to understand the actions of bacterial proteins that are localized on the surface of H. pylori. H.
pylori genomes contain more than 50 genes that are predicted to encode outer membrane proteins (OMPs).
Several OMPs have been reported to mediate H. pylori adherence to gastric epithelial cells, but the functions
of most H. pylori OMPs are not known. The overall hypothesis of this proposal is that H. pylori utilizes
specific OMPs at various stages of the infectious process to optimize initial colonization of the stomach and to
facilitate persistent colonization in the presence of a gastric mucosal inflammatory response, thereby
contributing to the development of gastric disease. The specific aims are (i) To define the role of two-
component signal transduction systems (TCSs) in regulating genes encoding OMPs, (ii) To define OMPs that
have a dominant role in promoting H. pylori colonization of the stomach, and (iii) To define temporal features of
processes by which specific OMPs promote H. pylori colonization of the stomach and modulate development
of gastric disease. To accomplish Aim 1, we will compare the transcriptomes of wild-type and mutant strains,
using RNA-seq and quantitative RT-PCR methods. To accomplish Aim 2, we will infect mice with a library of
strains containing mutations in OMP-encoding proteins, each labeled with a distinct nucleotide bar code, and
then will use high throughput sequencing to analyze the bacterial populations colonizing the stomach. To
accomplish Aim 3, we will regulate the expression of selected OMP-encoding genes in vivo through use of an
inducible promoter. Collectively, these experiments will provide important new insights into the roles of specific
OMPs in promoting initial colonization of the stomach, persistence and disease.

## Key facts

- **NIH application ID:** 9839368
- **Project number:** 5I01BX004447-02
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** TIMOTHY L COVER
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9839368

## Citation

> US National Institutes of Health, RePORTER application 9839368, Pathogenesis of Helicobacter pylori infection (5I01BX004447-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9839368. Licensed CC0.

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