Pathogenicity island-dependent activation of Rho GTPases Rac1 and Cdc42 in Helicobacter pylori infection
Pathogenicity island-dependent activation of Rho GTPases Rac1 and Cdc42 in Helicobacter pylori infection
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DOI：
10.1046/j.1365-2958.2001.02443.x
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发表时间：
2001-05-01
影响因子：
3.6
通讯作者：
Naumann, M
中科院分区：
文献类型：
--
作者：
Churin, Y;Kardalinou, E;Naumann, M
幽门螺杆菌（Helicobacter pylori，Hp）是引起慢性胃炎和十二指肠溃疡的主要病原体，在胃癌的发生发展中起重要作用。附H。幽门螺杆菌对胃上皮细胞的作用导致宿主细胞的核和细胞骨架反应。在此，我们发现Rho GTP酶Rad和Cdc42在胃上皮细胞感染野生型H. pylori或突变株cagA。相反，当H.使用缺乏功能性IV型分泌装置的幽门螺杆菌突变株（virB7和派）。我们证明了H. pylori诱导的Rad和Cdc42的激活导致介导核反应的p21激活激酶1（PAK 1）的激活，而突变株派对PAK 1活性没有影响。Rad、Cdc42和PAK1的激活代表了H.幽门。Rad和Cdc42被募集到细菌附着的位点，因此可能参与宿主细胞中局部和整体细胞骨架重排的调节。最后，肌动蛋白重排和上皮细胞运动在H。pylori感染依赖于由cag致病岛（派）编码的功能性IV型分泌系统的存在。
Helicobacter pylori has been identified as the major aetiological agent in the development of chronic gastritis and duodenal ulcer, and it plays a role in the development of gastric carcinoma. Attachment of H. pylori to gastric epithelial cells leads to nuclear and cytoskeletal responses in host cells. Here, we show that Rho GTPases Rad and Cdc42 were activated during infection of gastric epithelial cells with either the wild-type H. pylori or the mutant strain cagA. In contrast, no activation of Rho GTPases was observed when H. pylori mutant strains (virB7 and PAI) were used that lack functional type IV secretion apparatus. We demonstrated that H. pylori-induced activation of Rad and Cdc42 led to the activation of p21-activated kinase 1 (PAK1) mediating nuclear responses, whereas the mutant strain PAI had no effect on PAK1 activity. Activation of Rad, Cdc42 and PAK1 represented a very early event in colonization of gastric epithelial cells by H. pylori. Rad and Cdc42 were recruited to the sites of bacterial attachment and are therefore probably involved in the regulation of local and overall cytoskeleton rearrangement in host cells. Finally, actin rearrangement and epithelial cell motility in H. pylori infection depended on the presence of a functional type IV secretion system encoded by the cag pathogenicity island (PAI).