Current evidence implicates Helicobacter pylori as the etiological agent of type B gastritis. Colonization of the gastric mucosa by H. pylori is also associated with duodenal and gastric ulcers, and gastric carcinoma. However, little is known of the molecular mechanisms of mucosal colonization and even less of the virulence attributes of H. pylori which might contribute to disease. The long-term objective of the proposed work is to describe the mechanisms of pathogenesis by which H. pylori produces gastroduodenal diseases. One working hypothesis is that the range of clinical presentations associated with H. pylori infection could be attributed to individual strains possessing different virulence properties or combinations of virulence properties, with the reservation that there are also a number of host factors which could significantly influence the outcome of H. pylori infection.
The specific aims of the proposed work are [1] to determine the mechanisms by which different strains of H. pylori adhere to and colonize the gastric mucosa and to identify and characterize the various H. pylori adhesins in terms of receptor specificity, antigenicity and molecular composition; [2] to determine the role of H. pylori N-acetyl-neuraminyllactose-binding hemagglutinin (NLBH) adhesin in H. pylori virulence; [3] to use serological studies to determine the relative prevalence of the NLBH and other adhesins according to disease status, age, race, and socioeconomic factors; [4] to clone, identify and characterize all of the genes of H. pylori NLBH to the point of expression on the surface of E. coli; beginning with selection from genomic libraries, including cosmid libraries; and [5] to use a genetic approach to assess the prevalence of NLBH by surveying, using the PCR technique, H. pylori isolates from a large number of subjects with various gastroduodenal diseases. Also, experiments to confirm the role of the NLBH as a virulence factor will be carried out by constructing and testing NLBH- negative mutants of H. pylori.
