Expression cloning of cholesterol α-glucosyltransferase, a unique enzyme that can be inhibited by natural antibiotic gastric mucin O-glycans, from Helicobacter pylori
Expression cloning of cholesterol α-glucosyltransferase, a unique enzyme that can be inhibited by natural antibiotic gastric mucin O-glycans, from Helicobacter pylori
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DOI：
10.1016/j.bbrc.2006.08.145
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发表时间：
2006-11-03
影响因子：
3.1
通讯作者：
Fukuda, Minoru
中科院分区：
文献类型：
--
作者：
Lee, Heeseob;Kobayashi, Motohiro;Fukuda, Minoru
幽门螺杆菌感染了世界上一半以上的人口，但只有3%的感染者发展为消化性溃疡、胃癌和粘膜相关淋巴组织（MALT）淋巴瘤。In H. pylori中，α-葡糖基胆固醇构成细胞壁脂质的25%以上，并且已经表明α-葡糖基胆固醇对于H.幽门活力。在这里，我们确定了胆固醇α-葡萄糖基转移酶（CHL α GcT）使用表达克隆策略，并表明这种酶是明显抑制粘蛋白型O-聚糖类似于那些存在于胃粘膜的较深的部分。此外，通过同源重组使CHL α GcT失活导致H.幽门螺杆菌致死率这些结果表明，H.幽门螺杆菌CHL α GcT是一种独特的酶，被天然抗生素粘蛋白靶向，并构成了预防幽门螺杆菌的优良治疗靶点。幽门螺杆菌引起的消化性溃疡、胃癌和MALT淋巴瘤。(c)2006年爱思唯尔公司All rights reserved.
Helicobacter pylori infects over half the world's population, but only 3% of those infected develop peptic ulcer, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. In H. pylori, alpha-glucosyl cholesterol constitutes more than 25% of cell wall lipids, and it has been suggested that alpha-glucosyl cholesterol is essential for H. pylori viability. Here, we identified cholesterol alpha-glucosyltransferase (CHL alpha GcT) using an expression cloning strategy and showed that this enzyme is distinctively inhibited by mucin-type O-glycans similar to those present in deeper portions of the gastric mucosa. Moreover, inactivation of CHL alpha GcT by homologous recombination led to H. pylori lethality. These results indicate that H. pylori CHL alpha GcT is a unique enzyme targeted by a natural antibiotic mucin and constitutes an excellent therapeutic target to prevent H. pylori-induced peptic ulcer, gastric carcinoma, and MALT lymphoma. (c) 2006 Elsevier Inc. All rights reserved.