Correlation between cag pathogenicity island composition and Helicobacter pylori-associated gastroduodenal disease
Correlation between cag pathogenicity island composition and Helicobacter pylori-associated gastroduodenal disease
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DOI：
10.1128/iai.71.11.6573-6581.2003
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发表时间：
2003-11-01
影响因子：
3.1
通讯作者：
Engstrand, L
中科院分区：
文献类型：
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作者：
Nilsson, C;Sillén, A;Engstrand, L
幽门螺杆菌感染与多种结局有关，从表面上无症状的共存到消化性溃疡疾病和胃癌。CAG致病性岛(PAI)包含与更具侵袭性的表型相关的基因，已被认为是严重疾病结局的决定因素。CagA基因已经作为CAG PAI的一个标记，然而，这个单一基因的存在并不一定意味着存在一套完整的CAG PAI基因。我们分析了66株来自十二指肠溃疡、胃癌和非溃疡性消化不良患者的临床分离株的CAG PAI的组成。DNA与包含CAG PAI全部基因的芯片杂交显示，76%的菌株含有全部CAG PAI基因，9%的菌株不含CAG PAI基因。10株(15%)CAG PAI基因部分缺失，其中3株为cagA阴性。在AGS细胞中诱导IL-8产生的能力与完整的CAG PAL株的存在有关，该株株仅携带部分岛诱导的IL-8水平明显低于CAG PAI阳性菌株诱导的IL-8水平。CAG PAI的完整存在与更严重的病理发展相关，这种菌株在严重胃十二指肠疾病患者中更常见(优势比为5.13；95%可信区间为1.5至17.4)。CAG PAI的部分缺失似乎足以降低生物体的致病性。
Helicobacter pylori infection is associated with a variety of outcomes ranging from seemingly asymptomatic coexistence to peptic ulcer disease and gastric cancer. The cag pathogenicity island (PAI) contains genes associated with a more aggressive phenotype and has been suggested to be a determinant of severe disease outcome. The cagA gene has served as a marker for the cag PAL However, the presence of this single gene does not necessarily indicate the presence of a complete set of cag PAI genes. We have analyzed the composition of the cag PAI in 66 clinical isolates obtained from patients with duodenal ulcer, gastric cancer, and nonulcer dyspepsia. Hybridization of DNA to microarrays containing all the genes of the cag PAI showed that 76 and 9% of the strains contained all or none of the cag PAI genes, respectively. Partial deletions of the cag PAI were found in 10 isolates (15%), of which 3 were cagA negative. The ability to induce interleukin-8 (IL-8) production in AGS cells was correlated to the presence of a complete cag PAL Strains carrying only parts of the island induced IL-8 at levels significantly lower than those induced by cag PAI-positive isolates. The presence of an intact cag PAI correlates with development of more severe pathology, and such strains were found more frequently in patients with severe gastroduodenal disease (odds ratio, 5.13; 95% confidence interval, 1.5 to 17.4). Partial deletions of the cag PAI appear to be sufficient to render the organism less pathogenic.