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Helicobacter pylori  infection is the etiology of several gastric-related diseases including gastric cancer. Cytotoxin associated gene A (CagA), vacuolating cytotoxin A (VacA) and α-subunit of urease (UreA) are three major virulence factors of  H. pylori , and each of them has a distinct entry pathway and pathogenic mechanism during bacterial infection.  H. pylori  can shed outer membrane vesicles (OMVs). Therefore, it would be interesting to explore the production kinetics of  H. pylori  OMVs and its connection with the entry of key virulence factors into host cells. Here, we isolated OMVs from  H. pylori  26,695 strain and characterized their properties and interaction kinetics with human gastric adenocarcinoma (AGS) cells. We found that the generation of OMVs and the presence of CagA, VacA and UreA in OMVs were a lasting event throughout different phases of bacterial growth.  H. pylori  OMVs entered AGS cells mainly through macropinocytosis/phagocytosis. Furthermore, CagA, VacA and UreA could enter AGS cells via OMVs and the treatment with  H. pylori  OMVs would cause cell death. Comparison of  H. pylori  26,695 and clinical strains suggested that the production and characteristics of OMVs are not only limited to laboratory strains commonly in use, but a general phenomenon to most  H. pylori  strains.

international journal of molecular sciences

Outer Membrane Vesicle Production by Helicobacter pylori Represents an Approach for the Delivery of Virulence Factors CagA, VacA and UreA into Human Gastric Adenocarcinoma (AGS) Cells