Release of Helicobacter pylori vacuolating cytotoxin by both a specific secretion pathway and budding of outer membrane vesicles. Uptake of released toxin and vesicles by gastric epithelium.

The mechanisms by which Helicobacter pylori releases its virulence factors are poorly known. Active secretion has been proposed for some products, inc luding a vacuolating toxin (VacA), Outer membrane vesicles represent anothe r mechanism by which some Gram-negative bacteria may release virulence fact ors. This study sought to localize VacA by immunocytochemistry in H. pylori cells, to determine whether H.pylori produces outer membrane vesicles, and to investigate whether such vesicles might constitute a vehicle for the de livery of bacterial virulence factors to the gastric mucosa. Small (50-300 nm) membrane vesicles were found in H. pylori culture media from both H.pyl ori strain 60190 and strain CCUG 17874, These vesicles appeared to originat e from blebs arising on the bacterial outer membrane. VacA was immunolocali zed in the periplasm and outer membrane of intact bacteria and also in oute r membrane blebs and vesicles. Both soluble secreted VacA and VacA-containi ng vesicles bound to, and were internalized by, MKN28 cells and were detect able in the gastric mucosa from H. pylori-infected humans. The release of o uter membrane vesicles by H.pylori may represent a mechanism, additional to secretory pathways, for the delivery of bacterial toxins and antigens to t he gastric mucosa. Copyright (C) 1999 John Wiley & Sons, Ltd.