Helicobacter pylori Vacuolating Cytotoxin, VacA, Is Responsible for Gastric Ulceration

Abstract

Pathogenic strains of Helicobacter pylori produce a potent exotoxin, VacA, which causes progressive vacuolation as well as gastric injury. Most H. pylori strains secrete VacA into the extracellular space. After exposure of VacA to acidic or basic pH, re-oligomerized VacA (mainly 6 monomeric units) at neutral pH is more toxic. Although the mechanisms have not been defined, VacA induces multiple effects on epithelial and lymphatic cells, i.e., vacuolation with alterations of endo-lysosomal function, anion-selective channel formation, mitochondrial damage, and the inhibition of primary human CD4⁺ cell proliferation. VacA binds to two types of receptor-like protein tyrosine phosphatases (RPTP), RPTPα and RPTPβ, on the surface of target cells. Oral administration of VacA to wild-type mice, but not to RPTPβ KO mice, results in gastric ulcers, suggesting that RPTPβ is essential for intoxication of gastric tissue by VacA. As the potential roles of VacA as a ligand for RPTPα and RPTPβ are only poor understood, further studies are needed to determine the importance of VacA in the pathogenisis of disease due to H. pylori infection.

gastric ulcer, Helicobacter pylori, RPTP (receptor-like protein tyrosine phosphatase), VacA (vacuolating cytotoxin), vacuolation.