Helicobacter pylori VacA exhibits pleiotropic actions in host cells

Abstract

Helicobacter pylori vacuolating cytotoxin (VacA) is a major virulence factor, with pleiotropic actions on target cells including induction of vacuole formation, mitochondrial dysfunction leading to apoptosis, modulation of signal transduction pathways associated with autophagy, inhibition of T cell proliferation, and production of inflammatory cytokines. Numerous epidemiological studies have indicated that the allelic diversity within four variable regions of the vacA gene might be associated with cell type-specific binding as well as specific clinical outcomes in H. pylori infection. VacA binds to receptors such as receptor protein tyrosine phosphatases (RPTPα and RPTPβ), low-density lipoprotein receptor-related protein-1 (LRP1), fibronectin, CD18, and sphingomyelin to facilitate its action, suggesting the involvement of these receptors in the pathogenesis of H. pylori infection. RPTPβ contributes to ulceration in gastric epithelial cells and LRP1 is involved in the induction of autophagy. Interestingly, it has been suggested that CagA is degraded by VacA-induced autophagy and that the interaction between these two molecules is associated with the pathogenesis of gastric diseases. Therefore, better understanding of the mechanism of VacA toxicity may provide valuable information regarding appropriate medical care for gastroduodenal diseases caused by H. pylori infection.