# "Pathogenesis of Helicobacter pylori Infection"

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2024 · —

## Abstract

Helicobacter pylori is a Gram-negative bacterium that colonizes the human stomach. The presence of H. pylori
in the stomach is associated with an increased risk of gastric cancer and peptic ulcer disease. The World Health
Organization has classified H. pylori as a type I carcinogen, and gastric cancer is the fourth leading cause of
cancer-related death worldwide. H. pylori genomes contain more than 50 genes that are predicted to encode
outer membrane proteins. Six H. pylori genes encode non-identical OMPs designated as FecA- or FrpB-like
proteins. These six proteins are predicted to function as TonB-dependent transporters (TBDTs). TBDTs are outer
membrane proteins that bind and transport substrates through the outer membrane, using an energy-dependent
process requiring an inner membrane complex (TonB-ExbB-ExbD) that transduces energy (proton motive force)
to the outer membrane. Relatively little experimental work has been done to analyze the functions of the six
putative H. pylori TBDTs, but one is reported to have a role in nickel acquisition. In preliminary studies, we have
mutated H. pylori genes encoding each of the six putative TBDTs and genes encoding each of two non-identical
TonB proteins. Our preliminary experimental results confirm that one of the TBDTs (FrpB3) has a role in nickel
acquisition and support our hypothesis that TonB-dependent processes contribute to H. pylori iron acquisition.
In addition, our experimental results indicate that these proteins contribute to H. pylori fitness in vitro. The long-
term goals of this work are to understand the molecular mechanisms that allow H. pylori to persistently colonize
the human gastric mucosa, understand the molecular mechanisms by which H. pylori infection leads to the
development of gastric cancer or peptic ulceration, and develop effective strategies for the prevention of these
diseases. To achieve these long-term goals, we seek to understand the actions of proteins that are localized on
the surface of H. pylori and understand their roles in H. pylori acquisition of essential nutrients. The overall
hypothesis of this proposal is that FecA- and FrpB-like proteins have important roles in H. pylori nutrient metal
acquisition and contribute to H. pylori fitness in vivo, thereby influencing the capacity of H. pylori to colonize the
stomach and cause gastric disease. The specific aims are (i) to define the roles of FecA- and FrpB-like proteins
in H. pylori nutrient acquisition and fitness in vitro, and (ii) to define the roles of FecA- and FrpB-like proteins in
vivo. To accomplish Aim 1, we will further define the roles of FecA- and FrpB-like proteins and TonB proteins in
H. pylori nutrient metal acquisition; systematically analyze the regulation of fecA-like, frpB-like, and tonB genes;
and analyze multiple properties of mutant strains (harboring mutations in fecA-like, frpB-like, or tonB genes)
compared to wild-type and complemented mutant strains. To accomplish Aim 2, we will experimenta...

## Key facts

- **NIH application ID:** 10918527
- **Project number:** 2I01BX004447-05A2
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** TIMOTHY L COVER
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 2
- **Project period:** 2019-04-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10918527

## Citation

> US National Institutes of Health, RePORTER application 10918527, "Pathogenesis of Helicobacter pylori Infection" (2I01BX004447-05A2). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10918527. Licensed CC0.

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