The long term objectives of this project are to investigate the role Helicobacter pullorum in human gastrointestinal disease, to provide comprehensive training in molecular biology and in vivo models of pathogenesis for the candidate, and to prepare the candidate to become an independent investigator. H. pullorum is a newly described Helicobacter species which has been isolated from poultry and human patients with gastroenteritis. H. pullorum produces a novel cytotoxin originally discovered and characterized in H. hepaticus, which is distinct from the previously described vacuolating cytotoxin (VAC) found in other Helicobacter species, including H. pylori. Preliminary work indicates that this toxin may be in part responsible for the pathogenesis of H. hepaticus and by analogy, H. pullorum. The candidate proposes to purify and characterize the cytotoxin produced by H. pullorum. He then plans to isolate and characterize the gene encoding the cytotoxin from a library made from genomic H. pullorum DNA. Furthermore, the candidate proposes to develop a murine model for H. pullorum infection and to characterize the nature of the pathogenic changes caused by this infection. Through use of this animal model, the candidate plans to elucidate the role cytotoxin has in pathogenesis as well as determine other factors that contribute to the pathogenesis of H. pullorum.
