Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 30013, Taiwan.
Division of Gastroenterology, Department of Internal Medicine, Kaoshiung Medical University Hospital, Kaoshiung Medical University, Kaoshiung 80756, Taiwan.
Int J Mol Sci. 2021 Apr 11;22(8):3942. doi: 10.3390/ijms22083942.
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 , and each of them has a distinct entry pathway and pathogenic mechanism during bacterial infection. can shed outer membrane vesicles (OMVs). Therefore, it would be interesting to explore the production kinetics of OMVs and its connection with the entry of key virulence factors into host cells. Here, we isolated OMVs from 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. OMVs entered AGS cells mainly through macropinocytosis/phagocytosis. Furthermore, CagA, VacA and UreA could enter AGS cells via OMVs and the treatment with OMVs would cause cell death. Comparison of 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 strains.
感染是包括胃癌在内的几种胃部相关疾病的病因。细胞毒素相关基因 A(CagA)、空泡细胞毒素 A(VacA)和脲酶α亚单位(UreA)是幽门螺杆菌的三个主要毒力因子,它们在细菌感染过程中都有独特的进入途径和致病机制。幽门螺杆菌可以脱落外膜囊泡(OMVs)。因此,探索幽门螺杆菌 OMVs 的产生动力学及其与关键毒力因子进入宿主细胞的关系将是一件有趣的事情。在这里,我们从 26,695 株中分离出 OMVs,并对其特性及其与人类胃腺癌(AGS)细胞的相互作用动力学进行了表征。我们发现,OMVs 的产生以及 CagA、VacA 和 UreA 存在于 OMVs 中是细菌生长不同阶段的持续事件。OMVs 主要通过巨胞饮/吞噬作用进入 AGS 细胞。此外,CagA、VacA 和 UreA 可以通过 OMVs 进入 AGS 细胞,并且 OMVs 的处理会导致细胞死亡。与 26,695 株和临床株的比较表明,OMVs 的产生和特性不仅限于常用的实验室菌株,而是大多数 菌株的普遍现象。