Lindén Sara, Mahdavi Jafar, Hedenbro Jan, Borén Thomas, Carlstedt Ingemar
Mucosal Biology Group, Department of Cell and Molecular Biology, BMC/C13, Lund University, SE-22184 Lund, Sweden.
Biochem J. 2004 Dec 1;384(Pt 2):263-70. doi: 10.1042/BJ20040402.
Helicobacter pylori causes gastritis, peptic ulcer disease and gastric cancer. The microbe is found in the gastric mucus layer where a pH gradient ranging from acidic in the lumen to neutral at the cell surface is maintained. The aim of the present study was to investigate the effects of pH on H. pylori binding to gastric mucins from healthy individuals. At pH 3, all strains bound to the most charged MUC5AC glycoform and to a putative mucin of higher charge and larger size than subunits of MUC5AC and MUC6, irrespective of host blood-group. In contrast, at pH 7.4 only Le(b)-binding BabA-positive strains bound to Le(b)-positive MUC5AC and to smaller mucin-like molecules, including MUC1. H. pylori binding to the latter component(s) seems to occur via the H-type-1 structure. All strains bound to a proteoglycan containing chondroitin sulphate/dermatan sulphate side chains at acidic pH, whereas binding to secreted MUC5AC and putative membrane-bound strains occurred both at neutral and acidic pH. The binding properties at acidic pH are thus common to all H. pylori strains, whereas mucin binding at neutral pH occurs via the bacterial BabA adhesin and the Le(b) antigen/related structures on the glycoprotein. Our work shows that microbe binding to membrane-bound mucins must be considered in H. pylori colonization, and the potential of these glycoproteins to participate in signalling events implies that microbe binding to such structures may initiate signal transduction over the epithelial layer. Competition between microbe binding to membrane-bound and secreted mucins is therefore an important aspect of host-microbe interaction.
幽门螺杆菌可引发胃炎、消化性溃疡疾病以及胃癌。这种微生物存在于胃黏液层中，在该层中维持着从管腔酸性到细胞表面中性的pH梯度。本研究的目的是调查pH对幽门螺杆菌与健康个体胃黏蛋白结合的影响。在pH 3时，所有菌株均与电荷最多的MUC5AC糖型以及一种电荷更高、尺寸大于MUC5AC和MUC6亚基的假定黏蛋白结合，与宿主血型无关。相比之下，在pH 7.4时，只有结合Le(b)的BabA阳性菌株与Le(b)阳性MUC5AC以及包括MUC1在内的较小黏蛋白样分子结合。幽门螺杆菌与后一种成分的结合似乎是通过H-1型结构发生的。所有菌株在酸性pH下均与含有硫酸软骨素/硫酸皮肤素侧链的蛋白聚糖结合，而与分泌型MUC5AC和假定的膜结合型菌株的结合在中性和酸性pH下均会发生。因此，酸性pH下幽门螺杆菌的结合特性是所有菌株共有的，而中性pH下的黏蛋白结合是通过细菌黏附素BabA以及糖蛋白上的Le(b)抗原/相关结构发生的。我们的研究表明，在幽门螺杆菌定植过程中必须考虑微生物与膜结合型黏蛋白的结合，并且这些糖蛋白参与信号传导事件的潜力意味着微生物与此类结构的结合可能会引发上皮层的信号转导。因此，微生物与膜结合型和分泌型黏蛋白结合之间的竞争是宿主-微生物相互作用的一个重要方面。
