Helicobacter pylori strain-specific differences in genetic content, identified by microarray, influence host inflammatory responses
Helicobacter pylori strain-specific differences in genetic content, identified by microarray, influence host inflammatory responses
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DOI：
10.1172/jci11450
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发表时间：
2001-03-01
影响因子：
15.9
通讯作者：
Peek, RM
中科院分区：
文献类型：
--
作者：
Israel, DA;Salama, N;Peek, RM
幽门螺杆菌增加了溃疡病和胃癌的风险，但只有少数的H。幽门定殖的个体发生疾病。我们检查了两个H的能力。pylori分离株在体内或体外诱导不同的宿主反应，然后使用幽门螺杆菌全基因组微阵列鉴定与致病相关的细菌决定簇。胃溃疡菌株B128比十二指肠溃疡菌株G1.1更能诱导沙土鼠胃粘膜的严重胃炎、增殖和凋亡，并且胃溃疡和萎缩仅发生在B128（+）沙土鼠中。在体外，沙鼠传代B128衍生物显着增加IL-8的分泌和细胞凋亡相比，G1.1菌株。DNA杂交的微阵列确定了几个ST-雨特定的基因组成的差异，包括一个大的删除菌株G1.1中的cag致病岛。B128菌株中cag岛的部分和完全破坏在体外减弱了IL-8的诱导，并在体内显著降低了胃炎症。这些结果表明，H. pylori调节与炎症相关的上皮细胞反应依赖于完整的CAG致病岛的存在。使用H。pylori全基因组芯片是鉴定幽门螺杆菌基因含量差异的有效方法。pylori菌株在H.幽门感染
Helicobacter pylori enhances the risk for ulcer disease and gastric cancer, yet only a minority of H. pylori-colonized individuals develop disease. We examined the ability of two H. pylori isolates to induce differential host responses in vivo or in vitro, and then used an H, pylori whole genome microarray to identify bacterial determinants related to pathogenesis. Gastric ulcer strain B128 induced more severe gastritis, proliferation, and apoptosis in gerbil mucosa than did duodenal ulcer strain G1.1, and gastric ulceration and atrophy occurred only in B128(+) gerbils. In vitro, gerbil-passaged B128 derivatives significantly increased IL-8 secretion and apoptosis compared with G1.1 strains. DNA hybridization to the microarray identified several st-rain-specific differences in gene composition including a large deletion of the cag pathogenicity island in strain G1.1. Partial and complete disruption of the cag island in strain B128 attenuated induction of IL-8 in vitro and significantly decreased gastric inflammation in vivo. These results indicate that the ability of H. pylori to regulate epithelial cell responses related to inflammation depends on the presence of an intact cag pathogenicity island. Use of an H. pylori whole genome microarray is an effective method to identify differences in gene content between H. pylori strains that induce distinct pathological outcomes in a rodent model of H. pylori infection.