Vacuolating cytotoxin A (VacA)

Vacuolating cytotoxin A (VacA) is a potent exotoxin and major virulence factor secreted by the bacterium Helicobacter pylori, which colonizes the human stomach (UniProt P14739). The protein is synthesized as a large precursor that undergoes proteolytic processing to produce p33 and p55 subunits, which subsequently form high-molecular-weight oligomeric complexes (Cover & Blanke, 2005). These complexes insert into host cell membranes to create anion-selective channels, leading to the formation of large, acidic vacuoles and the disruption of endolysosomal trafficking (McClain et al., 2003). Beyond vacuolation, VacA induces mitochondrial damage, triggers apoptosis, and suppresses the immune response by inhibiting T-cell proliferation and activation (Palframan et al., 2012). Because of its critical role in the pathogenesis of gastric ulcers and gastric cancer, VacA is a primary target for the development of neutralizing antibodies, vaccines, and therapeutic inhibitors (Foegeding et al., 2016).

Other names

Vacuolating cytotoxin autotransporterVacuolating cytotoxinVacA proteinHelicobacter pylori VacA

Neutralization of toxin activity by blocking pore formation, inhibiting cell binding, or preventing the oligomerization of p33 and p55 subunits (Yahiro et al., 2015; Palframan et al., 2012).