Helicobacter pylori induces β3GnT5 in human gastric cell lines, modulating expression of the SabA ligand sialyl-Lewis x
Helicobacter pylori induces β3GnT5 in human gastric cell lines, modulating expression of the SabA ligand sialyl-Lewis x
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DOI：
10.1172/jc134324
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发表时间：
2008-06-01
影响因子：
15.9
通讯作者：
Reis, Celso A.
中科院分区：
文献类型：
--
作者：
Marcos, Nuno T.;Magalhaes, Ana;Reis, Celso A.
慢性幽门螺杆菌感染被认为是胃癌的一个原因。幽门螺杆菌与胃细胞的粘附是由细菌粘附素介导的，如唾液酸结合粘附素（SabA），它与碳水化合物结构sialyl-Lewis x结合。在持续的幽门螺杆菌感染期间，胃上皮中sialyl-Lewis x的表达被诱导，这表明幽门螺杆菌调节宿主细胞糖基化模式以增强粘附。在这里，我们评估了幽门螺杆菌感染后人类胃癌细胞系糖基化相关基因表达谱的变化。我们观察到，通过微阵列检测的1,031个人类基因中，幽门螺杆菌显著改变了168个基因的表达，这些改变的程度与幽门螺杆菌菌株的致病性有关。一种高致病性菌株改变了与聚糖生物合成有关的几个基因的表达，特别是编码β 3 GlcNAc T5 （β 3GnT5）的基因，这是Lewis抗原生物合成所必需的GlcNAc转移酶。β 3GnT5的诱导是针对携带cag致病性岛基因簇的高致病性幽门螺杆菌菌株的感染，并且依赖于CagA和CagE。此外，β 3GnT5在人胃癌细胞系中的过表达导致sialyl-Lewis x表达增加和幽门螺杆菌粘附。本研究确定了我们认为的幽门螺杆菌调节胃细胞中SabA配体的生物合成的新机制，从而加强了成功定植所必需的上皮附着。
Chronic Helicobacter pylori infection is recognized as a cause of gastric cancer. H. pylori adhesion to gastric cells is mediated by bacterial adhesins such as sialic acid-binding adhesin (SabA), which binds the carbohydrate structure sialyl-Lewis x. Sialyl-Lewis x expression in the gastric epithelium is induced during persistent H. pylori infection, suggesting that H. pylori modulates host cell glycosylation patterns for enhanced adhesion. Here, we evaluate changes in the glycosylation-related gene expression profile of a human gastric carcinoma cell line following H. pylori infection. We observed that H. pylori significantly altered expression of 168 of the 1,031 human genes tested by microarray, and the extent of these alterations was associated with the pathogenicity of the H. pylori strain. A highly pathogenic strain altered expression of several genes involved in glycan biosynthesis, in particular that encoding beta 3 GlcNAc T5 (beta 3GnT5), a GlcNAc transferase essential for the biosynthesis of Lewis antigens. beta 3GnT5 induction was specific to infection with highly pathogenic strains of H. pylori carrying a cluster of genes known as the cag pathogenicity island, and was dependent on CagA and CagE. Further, beta 3GnT5 overexpression in human gastric carcinoma cell lines led to increased sialyl-Lewis x expression and H. pylori adhesion. This study identifies what we believe to be a novel mechanism by which H. pylori modulates the biosynthesis of the SabA ligand in gastric cells, thereby strengthening the epithelial attachment necessary to achieve successful colonization.