In search of the Helicobacter pylori VacA mechanism of action

Helicobacter pylori secretes an similar to 88 kDa VacA toxin that is consid ered to be an important virulence factor in the pathogenesis of peptic ulce r disease. Over the past decade, research on the molecular mechanisms and b iological functions of VacA has generated a complex and often puzzling scen ario. VacA is secreted into the extracellular space and also is partially r etained on the bacterial cell surface, exists in monomeric and oligomeric f orms, and binds to multiple eukaryotic cell-surface receptors. The cellular effects induced by VacA include vacuolation, alteration of endo-lysosomal function, pore formation in the plasma membrane, apoptosis, and epithelial monolayer permeabilisation. VacA has been reported to target several differ ent cell components, including endocytic vesicles, mitochondria, the cytosk eleton, and epithelial cell-cell junctions. It remains unclear whether VacA should be classified as an A/B type toxin, a channel-forming toxin, or bot h. This review is intended to summarise our current knowledge about VacA, a nd to orient the reader to this fascinating and challenging research area. (C) 2001 Published by Elsevier Science Ltd.