Helicobacter pylori infection causes chronic active gastritis and peptic ulcer disease. In the western world, 10 percent of people (22.000.000 individuals) develop peptic ulcers. Furthermore, H. pylori infection is tightly correlated with development of gastric cancer with >500.000 mortalities/Y and, H. pylori has been defined a carcinogen by the WHO.
The project studies protein-carbohydrate interactions that mediate adherence of H. pylori to stomach tissue. We focus on the Blood Group Antigen Binding Adhesin, BabA, which is the key player attachment protein that targets H. pylori binding to the stomach lining. Bacterial adherence is mediated by high-affinity (strong) binding to carbohydrates such as ABO antigens (displayed by the common ABO-blood group system).
Our recent results demonstrate adaptation of H. pylori to changes in mucosal glycosylation patterns and, in addition, adaptation to ABO phenotypes in local population.
Structural identification of the detailed carbohydrate binding domains of the H. pylori BabA adhesin (crystals and NMR).
BabA will be analyzed for adaptation to host ABO phenotypes. Clones that have developed novel and adapted binding properties during infection of gastric mucosa will be identified by in vivo and in vitro selection.
H. pylori adhesin proteins will be developed into vaccine candidates. The animal model used is the transgenic "Lewis b mouse". Results can then be experimentally verified in human volunteers.