Analysis of the type IV secretion system-dependent cell motility of Helicobacter pylori-infected epithelial cells

Analysis of the type IV secretion system-dependent cell motility of Helicobacter pylori-infected epithelial cells
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DOI:
10.1016/j.bbrc.2004.07.199
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发表时间:
2004-09-24
影响因子:
3.1
通讯作者:
Naumann, M
Naumann, M
中科院分区:
生物学4区
文献类型:
--
作者:
Al-Ghoul, L;Wessler, S;Naumann, M

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幽门螺杆菌相关疾病的发病机制强烈依赖于由cag致病岛(派)编码的特化IV型分泌系统(T4 SS)。细胞毒素相关基因A(Cytotoxin-associated gene A,CagA)是目前已知的唯一一个H. pylori蛋白易位到宿主细胞中,随后通过宿主蛋白激酶进行酪氨酸磷酸化。H.幽门螺杆菌诱导派-或CagA-依赖性的细胞过程(例如,细胞运动性),PAI依赖性,但CagA非依赖性(例如,白细胞介素-8释放),或派和CagA非依赖性(例如,环氧合酶-2释放)。在这里,我们调查了H。pylori菌株中野生型菌株Hp 26695的单个派基因突变及其对细胞运动性的影响。在27个派基因中,有17个基因产物在运动发生的宿主细胞反应中起着重要的作用,5个PAI编码的蛋白质在运动发生的宿主细胞反应中起着重要的作用,而其余5个派基因产物对H.幽门感染这项研究清楚地表明,H。幽门螺杆菌诱导的细胞运动性和侵入性生长涉及IV型分泌系统依赖性信号传导以及易位和磷酸化的CagA。这些发现揭示了H. pylori对宿主细胞运动性的影响。(C)2004年爱思唯尔公司All rights reserved.
The pathogenesis of Helicobacter pylori-associated disorders is strongly dependent on a specialized type IV secretion system (T4SS) encoded by the cag pathogenicity island (PAI). Cytotoxin-associated gene A (CagA) is the only known H. pylori protein translocated into the host cell followed by tyrosine phosphorylation through host protein kinases. H. pylori induces cellular processes which are either PAI- or CagA-dependent (e.g., cell motility), PAI-dependent, but CagA-independent (e.g., interleukin-8 release), or PAI- and CagA-independent (e.g., cyclooxygenase-2 release). Here, we investigated H. pylori strains mutated in single PAI genes of the wild type strain Hp26695 and their effects on cell motility. We found 17 gene products out of 27 PAI genes playing a superordinated role and five PAI-encoded proteins exhibiting a clearly critical role in motogenic host cell responses, whereas the remaining five PAI gene products had no significant influence on the motogenic response in reaction to H. pylori infection. This study clearly demonstrated that H. pylori-induced cell motility and invasive growth involve type IV secretion system-dependent signalling as well as translocated and phosphorylated CagA. These findings reveal a deeper insight in to the meaning of the T4SS of H. pylori for host cell motility. (C) 2004 Elsevier Inc. All rights reserved.