Helicobacter pylori infection results in chronic superficial gastritis and plays an important role in the pathogenesis of duodenal and gastric ulcer disease. The chronic inflammatory process associated with the infection has also been linked to atrophic gastritis, gastric adenocarcinoma and non-Hodgkins lymphoma of the stomach. Infection is clinically silent in many, if not most, persons but its high prevalence worldwide results in substantial morbidity and mortality from peptic ulcer disease and gastric cancer. The factors that lead infected persons to develop clinical disease or remain asymptomatic are poorly understood. H. pylori strain-specific differences or variations in the host response to the infection alone, or in combination, may determine a particular pathologic outcome. The long term goals of this project are to gain an understanding of the inflammatory and immunologic events which develop in response to H. pylori infection, to identify host responses and strain-specific products that lead to distinct pathological outcomes, and to define the mechanisms by which specific bacterial products lead to divergent outcomes. To achieve these goals, the specific aims proposed are 1) to determine whether in vivo expression of the products of H. pylori strain-specific genes such as cagA and particular alleles of vacA, encoding the vacuolating cytotoxin induces characteristic patterns of cytokine production that are associated with peptic ulcer disease; 2) to identify and clone novel H. pylori genes that are induced by adherence to gastric epithelium, correlate gene expression with pathologic outcome, and examine the function of these genes; 3) to examine the effect of isogenic mutations within H. pylori virulence genes on cytokine production in vitro.
|Ando, T; Peek, R M; Pride, D et al. (2002) Polymorphisms of Helicobacter pylori HP0638 reflect geographic origin and correlate with cagA status. J Clin Microbiol 40:239-46|
|Israel, D A; Salama, N; Arnold, C N et al. (2001) Helicobacter pylori strain-specific differences in genetic content, identified by microarray, influence host inflammatory responses. J Clin Invest 107:611-20|
|Tham, K T; Peek Jr, R M; Atherton, J C et al. (2001) Helicobacter pylori genotypes, host factors, and gastric mucosal histopathology in peptic ulcer disease. Hum Pathol 32:264-73|
|Peek Jr, R M; Wirth, H P; Moss, S F et al. (2000) Helicobacter pylori alters gastric epithelial cell cycle events and gastrin secretion in Mongolian gerbils. Gastroenterology 118:48-59|
|Keates, S; Keates, A C; Warny, M et al. (1999) Differential activation of mitogen-activated protein kinases in AGS gastric epithelial cells by cag+ and cag- Helicobacter pylori. J Immunol 163:5552-9|
|Peek Jr, R M; Moss, S F; Tham, K T et al. (1997) Helicobacter pylori cagA+ strains and dissociation of gastric epithelial cell proliferation from apoptosis. J Natl Cancer Inst 89:863-8|
|Xu, Q; Peek Jr, R M; Miller, G G et al. (1997) The Helicobacter pylori genome is modified at CATG by the product of hpyIM. J Bacteriol 179:6807-15|