Around 1988, Leunk and colleagues discovered that supernatants from broth cultures of Helicobacter pylori induced massive vacuolar degeneration of various cultured epithelial cell lines (53). Since then, the nature of this toxic activity and its role in H. pylori-induced disease have been the subject of intensive study by a number of groups throughout the world. In 1992, the protein mediating the effect was purified and named the vacuolating cytotoxin (10). Determination of the amino-terminal sequence of the protein led, in 1994, to the cloning and sequencing of the toxin gene, which was designated vacA (13, 80, 90, 103). Following the initial characterization of the toxin and its gene, research has focused on VacA structure, the mechanisms underlying VacA's toxic activity, naturally occurring differences among VacA proteins produced by different strains of H. pylori, and the clinical importance of VacA polymorphism.
Interest in VacA has been intense, partly because of its potential as a novel tool for exploring aspects of eukaryotic cell biology, but mainly because of its putative role in the pathogenesis of H. pylori-associated diseases, in particular peptic ulceration and distal gastric adenocarcinoma. The precise role of VacA in these diseases is still under investigation, but VacA may contribute to the capacity of H. pylori to colonize and persist in the human gastric mucosa and may also contribute directly to gastric epithelial damage. Hence, VacA is currently a target for therapeutic intervention and a candidate for inclusion in a vaccine against H. pylori.
Copyright © 2001, ASM Press.