SabA is the H. pylori hemagglutinin and is polymorphic in binding to sialylated glycans.
SabA is the H. pylori hemagglutinin and is polymorphic in binding to sialylated glycans.
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SABA是幽门螺杆菌血凝素的H.
DOI：
10.1371/journal.ppat.0020110
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发表时间：
2006-10
期刊：
影响因子：
6.7
通讯作者：
Boren, Thomas
中科院分区：
文献类型：
--
作者：
Aspholm, Marina;Olfat, Farzad O.;Norden, Jenny;Sonden, Berit;Lundberg, Carina;Sjostrom, Rolf;Altraja, Siiri;Odenbreit, Stefan;Haas, Rainer;Wadstrom, Torkel;Engstrand, Lars;Semino-Mora, Cristina;Liu, Hui;Dubois, Andre;Teneberg, Susann;Arnqvist, Anna;Boren, Thomas
幽门螺杆菌对发炎胃粘膜的粘附依赖于宿主细胞表面上的唾液酸结合粘附素（SabA）和同源唾液酸化/岩藻糖基化聚糖。通过原位杂交技术，H.幽门螺杆菌在感染的人和恒河猴胃粘膜固有层的毛细血管和毛细血管后微静脉中与红细胞密切相关。H.幽门螺杆菌感染红细胞可能需要类似于红细胞的唾液酸依赖性体外凝集的分子机制（即，唾液酸依赖性血凝）。在这种情况下，SabA粘附素被确定为唾液酸依赖性血凝素的基础上唾液酸酶敏感的血凝，结合唾液酸化糖缀合物的测定，和一系列的同基因sabA缺失突变体的分析。红细胞膜上的SabA的结合位点的地形介绍映射到神经节苷脂与扩展的核心链。然而，受体图谱显示NeuAcα2- 3Gal-二糖构成SabA结合所需的最小唾液酸化结合表位。此外，临床分离株表现出多态性的唾液酸结合和sabA突变体的互补分析表明，多态性的唾液酸结合是SabA蛋白本身的固有特性。胃炎症与粘膜唾液酸化模式组成的周期性变化有关。我们认为，在持续感染过程中唾液酸结合特性的动态适应专门H。幽门螺杆菌的个体差异，粘膜糖基化和嗜性局部地区的发炎和/或发育不良组织。幽门螺杆菌感染在世界范围内非常常见，并引起胃的慢性炎症（胃炎），这可能会发展为消化性溃疡和胃癌。在胃上皮中，H.幽门螺杆菌感染诱导炎症相关的“唾液酸化”碳水化合物的表达。结合糖基化上皮细胞的能力被认为是H.幽门螺杆菌引起持续感染和疾病。在这里，作者表明，在建立感染，H。幽门螺杆菌还与受感染的人和恒河猴的胃粘膜血管中的红细胞结合。作者发现，“唾液酸结合粘附素”（SabA）是介导H。幽门螺杆菌转化为红细胞此外，他们表明，临床H。幽门螺杆菌分离株在它们结合各种唾液酸化碳水化合物的能力上表现出“多态性”，并且结合特性的变化取决于唾液酸结合粘附素蛋白本身。这种可变性可以适应H的结合特性。pylori对个体宿主的影响以及慢性炎症期间上皮糖基化模式的变化。在持续感染期间持续适应发炎组织可能是微生物病原体的一般特征，尽管它们的结合特性尚未被详细探索。
Adherence of Helicobacter pylori to inflamed gastric mucosa is dependent on the sialic acid–binding adhesin (SabA) and cognate sialylated/fucosylated glycans on the host cell surface. By in situ hybridization, H. pylori bacteria were observed in close association with erythrocytes in capillaries and post-capillary venules of the lamina propria of gastric mucosa in both infected humans and Rhesus monkeys. In vivo adherence of H. pylori to erythrocytes may require molecular mechanisms similar to the sialic acid–dependent in vitro agglutination of erythrocytes (i.e., sialic acid–dependent hemagglutination). In this context, the SabA adhesin was identified as the sialic acid–dependent hemagglutinin based on sialidase-sensitive hemagglutination, binding assays with sialylated glycoconjugates, and analysis of a series of isogenic sabA deletion mutants. The topographic presentation of binding sites for SabA on the erythrocyte membrane was mapped to gangliosides with extended core chains. However, receptor mapping revealed that the NeuAcα2–3Gal-disaccharide constitutes the minimal sialylated binding epitope required for SabA binding. Furthermore, clinical isolates demonstrated polymorphism in sialyl binding and complementation analysis of sabA mutants demonstrated that polymorphism in sialyl binding is an inherent property of the SabA protein itself. Gastric inflammation is associated with periodic changes in the composition of mucosal sialylation patterns. We suggest that dynamic adaptation in sialyl-binding properties during persistent infection specializes H. pylori both for individual variation in mucosal glycosylation and tropism for local areas of inflamed and/or dysplastic tissue. Helicobacter pylori infections are very common worldwide and cause chronic inflammation in the stomach (gastritis), which may progress to peptic ulcer disease and stomach cancer. In the gastric epithelium, H. pylori infections induce expression of inflammation-associated “sialylated” carbohydrates. The ability to bind to the glycosylated epithelial cells is considered to be essential for H. pylori to cause persistent infection and disease. Here the authors show that during established infection, H. pylori also binds to red blood cells in gastric mucosal blood vessels in both infected humans and Rhesus monkeys. The authors found that “sialic acid–binding adhesin” (SabA), is the bacterial surface protein that mediates binding of H. pylori to red blood cells. Furthermore, they show that clinical H. pylori isolates demonstrate “polymorphism” in their abilities to bind various sialylated carbohydrates, and that the variation in binding properties depends on the sialic acid–binding adhesin protein itself. This variability may adapt the binding properties of H. pylori both to individual hosts and the changing epithelial glycosylation patterns during chronic inflammation. Continuous adaptation to inflamed tissue during persistent infections is probably a general feature of microbial pathogens, although their binding properties have not yet been explored in detail.
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影响因子：
37.8
作者：
Desvarieux, M;Demmer, RT;Papapanou, PN
通讯作者：
Papapanou, PN
影响因子：
3.2
作者：
EVANS, DG;KARJALAINEN, TK;LEE, CH
通讯作者：
LEE, CH
DOI：
10.1073/pnas.0404817101
发表时间：
2004-11-30
影响因子：
11.1
作者：
Bäckström, A;Lundberg, C;Arnqvist, A
通讯作者：
Arnqvist, A
影响因子：
3.1
作者：
EVANS, DG;EVANS, DJ;GRAHAM, DY
通讯作者：
GRAHAM, DY
DOI：
10.1073/pnas.96.22.12778
发表时间：
1999-10-26
影响因子：
11.1
作者：
Gerhard, M;Lehn, N;Prinz, C
通讯作者：
Prinz, C