Although most H. pylori-infected persons never develop upper gastrointestinal symptoms, some develop peptic ulcer disease or gastric malignancies. The factors that determine whether or not peptic ulceration occurs in H. pylori-infected persons are not yet well understood. The hypothesis of the current proposal is that H. pylori strains associated with peptic ulcer disease exhibit genetic characteristics that are different from those of non-ulcerogenic strains. Our previous investigations of this topic have focused on vaeA allelic variation and presence/absence of the eag pathogenicity island as bacterial factors that account for differences in disease outcome among H. pylori-infected persons. However, it seems likely that additional strain-specific H. pylori factors might help to determine whether or not peptic ulceration occurs. In particular, diversity among strains in outer membrane protein expression would be expected to have important consequences for bacteria-host interactions. Several studies have suggested that H. pylori strains expressing BabA (an outer membrane protein that binds Lewis b) are associated with an increased risk for peptic ulcer disease. In addition, we present preliminary data indicating that H. pylori strains containing type I hopQ alleles are associated with an increased risk for peptic ulcer disease compared to strains containing type II hopQ alleles. We describe plans to investigate the expression, structure, and functions of these two outer membrane proteins.
The specific aims of this proposal are (i) to investigate the expression and structure of the H. pylori Lewis b-binding adhesin BabA (a prototype for the Hop family of H. pylori outer membrane proteins); (ii) to investigate allelic diversity and expression of H. pylori hopQ. These studies should result in a better understanding of the H. pylori factors that help to determine clinical outcome, and ultimately, may lead to advances in the treatment or prevention of H. pylori-associated human diseases. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK053623-09
Application #
7057861
Study Section
Special Emphasis Panel (ZRG1-BM-1 (02))
Program Officer
Hamilton, Frank A
Project Start
1997-09-30
Project End
2008-04-30
Budget Start
2006-05-01
Budget End
2008-04-30
Support Year
9
Fiscal Year
2006
Total Cost
$214,550
Indirect Cost
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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Loh, John T; Torres, Victor J; Cover, Timothy L (2007) Regulation of Helicobacter pylori cagA expression in response to salt. Cancer Res 67:4709-15
Lee, Woo-Kon; Ogura, Keiji; Loh, John T et al. (2006) Quantitative effect of luxS gene inactivation on the fitness of Helicobacter pylori. Appl Environ Microbiol 72:6615-22

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