Strain- and blood group-dependent binding of Helicobacter pylori to human gastric MUC5AC glycoforms
Strain- and blood group-dependent binding of Helicobacter pylori to human gastric MUC5AC glycoforms
复制标题
DOI：
10.1053/gast.2002.37076
复制
发表时间：
2002-12-01
期刊：
影响因子：
29.4
通讯作者：
Carlstedt, I
中科院分区：
文献类型：
--
作者：
Lindén, S;Nordman, H;Carlstedt, I
背景与目的：在胃中，幽门螺杆菌存在于粘液层和粘附在胃上皮上。本研究的目的是表征幽门螺杆菌与人胃粘蛋白的结合。方法：结合 Lewis(b) (Le(b)) 结构（通过 BabA 粘附素）和/或唾液酸化结构的幽门螺杆菌菌株，以及同基因粘附缺失突变体，用于鉴定微生物结合粘蛋白。通过密度梯度离心分离出 5 名健康个体的胃粘蛋白，并使用基于微量滴定的技术研究了中性 pH 条件下幽门螺杆菌的结合情况。结果：表达 BabA 粘附素的幽门螺杆菌菌株显示出与表达 Le(b) 抗原的个体中的 MUC5AC 粘蛋白结合。通过离子交换色谱进一步分级显示 Le(b) 阳性 MUC5AC 糖型，其受体特性对于不同的幽门螺杆菌菌株不同。研究的幽门螺杆菌菌株均未与 Le(b) 阴性个体的粘蛋白结合。然而，所有菌株均与梯度顶部的低密度、非粘蛋白、Le(b) 阴性材料结合。结论：幽门螺杆菌与从健康个体分离的人胃 MUC5AC 的结合是 BabA 依赖性的，并由粘蛋白呈现的 Le(b) 结构介导。然而，BabA 粘附素在与 Le(b) 取代的 MUC5AC 糖型结合方面表现出菌株依赖性偏好，从而在宿主-微生物相互作用中存在巨大的个体间差异。
Background & Aims: In the stomach, Helicobacter pylori is found both in the mucus layer and adhering to the gastric epithelium. The aim of this study is to characterize the binding of H. pylori to human gastric mucins. Methods: H. pylori strains that bind the Lewis(b) (Le(b)) structure (via the BabA adhesin) and/or sialylated structures, along with isogenic adhesion deletion mutants, were used to identify microbe-binding mucins. Gastric mucins from 5 healthy individuals, isolated by density-gradient centrifugation, were investigated for H. pylori binding at neutral pH using a microtiter-based technique. Results: H. pylori strains that express the BabA adhesins were shown to bind to the MUC5AC mucin in individuals expressing the Le(b) antigen. Further fractionation with an ion-exchange chromatography revealed Le(b)-positive MUC5AC glycoforms that differed in their receptor properties for different H. pylori strains. None of the H. pylori strains studied bound to mucins from Le(b)-negative individuals. However, all strains bound to low-density, nonmucin, Le(b)-negative material on top of the gradients. Conclusions: Binding of H. pylori to human gastric MUC5AC isolated from healthy individuals is BabA dependent and mediated by the Le(b) structure presented by the mucin. However, the BabA adhesins demonstrate strain-dependent preference in binding to MUC5AC glycoforms substituted with Le(b), allowing for great interindividual variability in host-microbe interactions.