title: In search of the Helicobacter pylori VacA mechanism of action.
abstract: Helicobacter pylori secretes an approximately 88 kDa VacA toxin that is considered to be an important virulence factor in the pathogenesis of peptic ulcer disease. Over the past decade, research on the molecular mechanisms and biological functions of VacA has generated a complex and often puzzling scenario. VacA is secreted into the extracellular space and also is partially retained on the bacterial cell surface, exists in monomeric and oligomeric forms, 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 different cell components, including endocytic vesicles, mitochondria, the cytoskeleton, and epithelial cell-cell junctions. It remains unclear whether VacA should be classified as an A/B type toxin, a channel-forming toxin, or both. This review is intended to summarise our current knowledge about VacA, and to orient the reader to this fascinating and challenging research area.
authors.affiliation: Department of Biomedical Science and Human Oncology, Section of General Pathology, University of Bari, P.zza G. Cesare 11, 70124, Bari, Italy. papinie@civ.bio.unipd.it
authors.forename: E
authors.initials: E
authors.lastname: Papini
authors.forename: M
authors.initials: M
authors.lastname: Zoratti
authors.forename: T L
authors.initials: TL
authors.lastname: Cover
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000633:toxicity*; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism / Q000633:toxicity*; D016480:Helicobacter pylori / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000648:ultrastructure; D014617:Vacuoles / Q000187:drug effects / Q000648:ultrastructure
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D007473:Ion Channels; C074689:VacA protein, Helicobacter pylori