title: Free-soluble and outer membrane vesicle-associated VacA from Helicobacter pylori: Two forms of release, a different activity.
abstract: Helicobacter pylori releases VacA both as free-soluble and as outer membrane vesicle (OMV)-associated toxin. In this study, we investigated the amount of VacA released in each of the two forms and the role of each form in VacA-induced cell vacuolation in vitro. We found that: (1) free-soluble toxin accounted for about 75% of released VacA, while the remaining 25% was OMV-associated; (2) although OMV-associated VacA caused a statistically significant vacuolation, virtually all the vacuolating activity of a H. pylori broth culture filtrate was due to free-soluble VacA. While it is widely accepted that OMVs may represent an important vehicle for delivering virulence factors to the gastric mucosa, our results suggest that OMV-associated VacA could play a pathobiological role different from that of free-soluble toxin. This conclusion fits with mounting evidence that VacA exerts a large pattern of pathobiological effects among which cell vacuolation might not be the main one.
authors.affiliation: Department of Experimental Medicine, Human Physiology Section, Pavia University, Pavia, Italy. vricci@unipv.it
authors.forename: Vittorio
authors.initials: V
authors.lastname: Ricci
authors.forename: Valentina
authors.initials: V
authors.lastname: Chiozzi
authors.forename: Vittorio
authors.initials: V
authors.lastname: Necchi
authors.forename: Amanda
authors.initials: A
authors.lastname: Oldani
authors.forename: Marco
authors.initials: M
authors.lastname: Romano
authors.forename: Enrico
authors.initials: E
authors.lastname: Solcia
authors.forename: Ulderico
authors.initials: U
authors.lastname: Ventura
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000032:analysis / Q000378:metabolism / Q000633:toxicity; D001426:Bacterial Proteins / Q000032:analysis* / Q000378:metabolism / Q000633:toxicity*; D001427:Bacterial Toxins / Q000032:analysis* / Q000378:metabolism / Q000633:toxicity*; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000187:drug effects / Q000648:ultrastructure; D006367:HeLa Cells; D016480:Helicobacter pylori / Q000472:pathogenicity* / Q000648:ultrastructure; D006801:Humans; D022142:Secretory Vesicles / Q000737:chemistry*; D014617:Vacuoles / Q000187:drug effects / Q000648:ultrastructure
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; C074689:VacA protein, Helicobacter pylori