VacA Background Information Helicobacter pylori is a spiral shaped bacterium that accounts for 80% of stomach ulcers and more than 90% of duodenal ulcers. Infection with Helicobacter pylori is also associated with the development of gastric cancer. The vacuolating toxin VacA is a major determinant of Helicobacter pylori associated gastric disease. In non-polarized cells, VacA alters the endocytic pathway, resulting in the release of acid hydrolases and the reduction of both extracellular ligand degradation and antigen processing. The toxin forms transmembrane anion-specific channels and reduces the transepithelial electrical resistance of polarized monolayers. Localization of the VacA channels in acidic intracellular compartments causes osmotic swelling, which, together with membrane fusion, leads to vacuole formation. This protein has recently been shown to be an important antigen in the human immune response to Helicobacter pylori infection. Cytotoxin associated gene A, also known as CagA, is closely associated with VacA. CagA induces morphological changes in the host, as well as inducing Actin reorganization, variations in the cell cycle and autocrine effects.
