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. ? ?

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BM-1 (02))
Program Officer
Hamilton, Frank A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Vanderbilt University Medical Center
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Yakoob, Javed; Abbas, Zaigham; Khan, Rustam et al. (2016) Helicobacter pylori outer membrane protein Q allele distribution is associated with distinct pathologies in Pakistan. Infect Genet Evol 37:57-62
Loh, John T; Torres, Victor J; Algood, Holly M Scott et al. (2008) Helicobacter pylori HopQ outer membrane protein attenuates bacterial adherence to gastric epithelial cells. FEMS Microbiol Lett 289:53-8
Wang, Fengsong; Xia, Peng; Wu, Fang et al. (2008) Helicobacter pylori VacA disrupts apical membrane-cytoskeletal interactions in gastric parietal cells. J Biol Chem 283:26714-25
Ding, Song-Ze; Olekhnovich, Igor N; Cover, Timothy L et al. (2008) Helicobacter pylori and mitogen-activated protein kinases mediate activator protein-1 (AP-1) subcomponent protein expression and DNA-binding activity in gastric epithelial cells. FEMS Immunol Med Microbiol 53:385-94
Torres, Victor J; VanCompernolle, Scott E; Sundrud, Mark S et al. (2007) Helicobacter pylori vacuolating cytotoxin inhibits activation-induced proliferation of human T and B lymphocyte subsets. J Immunol 179:5433-40
Algood, Holly M Scott; Gallo-Romero, Judith; Wilson, Keith T et al. (2007) Host response to Helicobacter pylori infection before initiation of the adaptive immune response. FEMS Immunol Med Microbiol 51:577-86
Chaturvedi, Rupesh; Asim, Mohammad; Lewis, Nuruddeen D et al. (2007) L-arginine availability regulates inducible nitric oxide synthase-dependent host defense against Helicobacter pylori. Infect Immun 75:4305-15
Algood, Holly M Scott; Torres, Victor J; Unutmaz, Derya et al. (2007) Resistance of primary murine CD4+ T cells to Helicobacter pylori vacuolating cytotoxin. Infect Immun 75:334-41
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
Busler, Valerie J; Torres, Victor J; McClain, Mark S et al. (2006) Protein-protein interactions among Helicobacter pylori cag proteins. J Bacteriol 188:4787-800

Showing the most recent 10 out of 47 publications