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首页> 外文期刊>Infection and immunity >Functional Analysis of the cag Pathogenicity Island in Helicobacter pylori Isolates from Patients with Gastritis, Peptic Ulcer, and Gastric Cancer
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Functional Analysis of the cag Pathogenicity Island in Helicobacter pylori Isolates from Patients with Gastritis, Peptic Ulcer, and Gastric Cancer

机译：胃炎，消化性溃疡和胃癌患者幽门螺杆菌分离物中cag致病岛的功能分析

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Helicobacter pylori is the causative agent of a variety of gastric diseases, but the clinical relevance of bacterial virulence factors is still controversial. Virulent strains carrying the cag pathogenicity island (cagPAI) are thought to be key players in disease development. Here, we have compared cagPAI-dependent in vitro responses in H. pylori isolates obtained from 75 patients with gastritis, peptic ulcer, and gastric cancer (n = 25 in each group). AGS gastric epithelial cells were infected with each strain and assayed for (i) CagA expression, (ii) translocation and tyrosine phosphorylation of CagA, (iii) c-Src inactivation, (iv) cortactin dephosphorylation, (v) induction of actin cytoskeletal rearrangements associated with cell elongation, (vi) induction of cellular motility, and (vii) secretion of interleukin-8. Interestingly, we found high but similar prevalences of all of these cagPAI-dependent host cell responses (ranging from 56 to 80%) among the various groups of patients. This study revealed CagA proteins with unique features, CagA subspecies of various sizes, and new functional properties for the phenotypic outcomes. We further showed that induction of AGS cell motility and elongation are two independent processes. Our data corroborate epidemiological studies, which indicate a significant association of cagPAI presence and functionality with histopathological findings in gastritis, peptic ulcer, and gastric cancer patients, thus emphasizing the importance of the cagPAI for the pathogenicity of H. pylori. Nevertheless, we found no significant association of the specific H. pylori-induced responses with any particular patient group. This may indicate that the determination of disease development is highly complex and involves multiple bacterial and/or host factors.
机译：幽门螺杆菌是多种胃病的病原，但细菌毒力因子的临床相关性仍存在争议。携带 cag 致病岛（ cag PAI）的强毒株被认为是疾病发展的关键因素。在这里，我们比较了 H PAI依赖的体外反应。从75例胃炎，消化性溃疡和胃癌患者中分离出幽门螺杆菌（每组中的 n = 25）。将AGS胃上皮细胞感染每种菌株并分析（i）CagA表达，（ii）CagA的易位和酪氨酸磷酸化，（iii）c-Src失活，（iv）皮质肌动蛋白去磷酸化，（v）肌动蛋白细胞骨架重排的诱导与细胞伸长有关，（vi）诱导细胞运动，以及（vii）分泌白细胞介素8。有趣的是，我们发现所有这些 cag PAI依赖的宿主细胞应答在各个患者组中的发生率都很高，但相似率很高（从56％到80％）。这项研究揭示了具有独特特征的CagA蛋白，各种大小的CagA亚种以及表型结果的新功能特性。我们进一步表明，AGS细胞运动性和伸长的诱导是两个独立的过程。我们的数据证实了流行病学研究，这些研究表明 cag PAI的存在和功能与胃炎，消化性溃疡和胃癌患者的组织病理学发现之间存在显着关联，因此强调了 cag 的重要性em> PAI对 H的致病性。幽门炎。然而，我们发现特定的 H没有显着关联。幽门螺杆菌引起的任何特定患者群体的反应。这可能表明疾病发展的确定非常复杂，涉及多种细菌和/或宿主因素。

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