Interaction of Helicobacter pylori VacA toxin with its target cells.

H. pylori infection is one of the most common bacterial infections worldwide and represents the greatest risk factor for gastric malignancy. The relevance of H. pylori for gastric cancer development is equivalent to that of tobacco smoking for lung cancer. Among the virulence factors of this bacterium, the protein toxin VacA plays a pivotal role in the overall strategy of H. pylori towards achieving persistent gastric colonization and significantly contributes to the pathogenesis of gastric cancer andpepticulcer disease.VacAisclassified asapore-forming toxin. Because it exerts many pleiotropic effects on mammalian cells and tissues, VacA has been proposed as a paradigm for toxin multifunctionality. Nevertheless, most of its effects on host cells depend on its channel-forming activity in intracellular sites. Thus, VacA has been also envisaged as a new type of A–B toxins (in which the A subunit exhibits pore-forming instead of enzymatic activity) acting intracellularly as a cell-invasive chloride channel. This chapter focuses on the molecular mechanisms through which VacA binds to, is internalized by, and exerts multiple effects in its target cells of the human host.