Persistent colonization of the human stomach with the Gram negative bacterium Helicobacter pylori is a risk factor for the development of gastric cancer and peptic ulcer disease. The long-term goals of this work are to understand the molecular mechanisms by which H. pylori causes these diseases, and to develop effective means for the prevention and treatment of these diseases. H. pylori isolates from different humans exhibit a considerable level of genetic diversity. One chromosomal region that is present in some H. pylori strains but not others is the cag pathogenicity island (PAI), a 40 kb region that is predicted to encode 27 different proteins. The incidence of symptomatic gastroduodenal disease (gastric cancer or peptic ulceration) is higher among persons infected with cag PAI-positive strains than among persons infected with cag-negative strains. The cag PAI encodes an effector protein, CagA, and multiple proteins that translocate CagA into gastric epithelial cells via a type IV secretion process. This project describes plans to investigate the molecular mechanisms by which CagA is translocated into gastric epithelial cells.
The aims of the project are i) to analyze subassemblies of the cag PAI-encoded type IV secretion apparatus;ii) to investigate the subcellular localization of H. pylori Cag proteins;and iii) to analyze effects of CagA in the stomachs of animal models. These studies should lead to important advances in our understanding of the molecular mechanisms by which products of the H. pylori cag PAI contribute to the development of gastroduodenal diseases. The presence of a bacterium known as Helicobacter pylori in the human stomach contributes to the development of cancer of the stomach and peptic ulcer disease. This research seeks to understand how a bacterial infection can lead to these diseases. The long-term goals are to develop effective means for the prevention and treatment of stomach cancer and peptic ulcer disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI068009-05
Application #
8268138
Study Section
Bacterial Pathogenesis Study Section (BACP)
Program Officer
Mills, Melody
Project Start
2008-04-15
Project End
2014-03-30
Budget Start
2012-04-01
Budget End
2014-03-30
Support Year
5
Fiscal Year
2012
Total Cost
$376,113
Indirect Cost
$131,088
Name
Vanderbilt University Medical Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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Gaddy, Jennifer A; Radin, Jana N; Loh, John T et al. (2013) High dietary salt intake exacerbates Helicobacter pylori-induced gastric carcinogenesis. Infect Immun 81:2258-67
Radin, Jana N; Gaddy, Jennifer A; Gonzalez-Rivera, Christian et al. (2013) Flagellar localization of a Helicobacter pylori autotransporter protein. MBio 4:e00613-12

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