THE VACUOLATING CYTOTOXIN OF HELICOBACTER-PYLORI

Helicobacter pylori, the causative agent of chronic superficial gastri tis and duodenal ulcer disease in humans, produces a unique cytotoxin (VacA) that induces cytoplasmic vacuolation in eukaryotic cells. The s tructural organization and processing of the vacuolating cytotoxin are characteristic of a family of proteins exemplified by Neisseria gonor rhoeae IgA protease. Although only 50% of H. pylori isolates produce d etectable cytotoxin activity in vitro, vacA homologues are present in virtually all isolates. Several families of vacA alleles have been ide ntified, and there is a strong correlation between presence of specifi c vacA genotypes, cytotoxin activity, and peptic ulceration. Experimen ts in a mouse model of H. pylori-induced gastric damage indicate that the cytotoxin plays an important role in inducing gastric epithelial n ecrosis.