TY - JOUR
T1 - 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
AU - Chew, Yongyu
AU - Chung, Hsin Yu
AU - Lin, Po Yi
AU - Wu, Deng Chyang
AU - Huang, Shau Ku
AU - Kao, Mou Chieh
N1 - Funding Information:
Acknowledgments: We thank the technical support from Ya-Hsien Chou at the confocal imaging core in National Tsing Hua University (sponsored by MOST 110-2731-M-007-001).
Funding Information:
Funding: This research was funded by: Ministry of Science and Technology, Taiwan (MOST), grant number MOST 107-2313-B-007-002-MY3; Academia Sinica, Taiwan, grant number AS-105-TP-B05; and National Tsing Hua University, grant number 109Q2516E1.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/4/2
Y1 - 2021/4/2
N2 - 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 pres-ence 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. Fur-thermore, 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.
AB - 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 pres-ence 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. Fur-thermore, 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.
KW - CagA
KW - Gastrointestinal disorders
KW - Helicobacter pylori
KW - Outer membrane vesicles
KW - UreA
KW - VacA
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UR - http://www.scopus.com/inward/citedby.url?scp=85103818115&partnerID=8YFLogxK
U2 - 10.3390/ijms22083942
DO - 10.3390/ijms22083942
M3 - Article
C2 - 33920443
AN - SCOPUS:85103818115
SN - 1661-6596
VL - 22
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 8
M1 - 3942
ER -
