Helicobacter pylori Vacuolating Toxin

The vacuolating cytotoxin (VacA) was one of the first H. pylori virulence factors identified. All H. pylori strains contain a vacA gene, but there is variation among H. pylori strains in the levels of VacA secretion and activity of VacA proteins. Strains containing allelic types of vacA that produce more active forms of the toxin are associated with human gastroduodenal disease. Experiments in animal models suggest that VacA may contribute to H. pylori colonization of the stomach, and the toxin has been linked to gastric epithelial damage. VacA induces a variety of effects in cultured epithelial cells, including alterations in membrane trafficking within the endolysosomal system, mitochondrial dysfunction, and cell death. Most VacA effects on cells are a consequence of intracellular toxin activities. Unlike most intracellular-acting bacterial toxins that enzymatically modify target molecules within eukaryotic cells, VacA causes cellular alterations primarily through the formation of intracellular ion-conducting channels. In this chapter, we review the structure and function of VacA, along with the roles of VacA in the pathogenesis of H. pylori-associated diseases.