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Carbohydrates in Helicobacter pylori infection

摘要Objective To study the role of carbohydrates in Helicobacter pylori (H. pylori) infection. Furthermore, this article gives a review of H. pylori therapy and discussion of the development carbohydrate drugs against H. pylori.Methods An English-language literature search was made using MEDLINE (1997-1986). Fifty-one papers were selceted that specifically addressed the stated purpose.Results Helicobacter pylori plays a causative role in the pathogenesis of gastritis, gastric atrophy, and peptic and duodenal ulcer. Infection caused by this bacterium is also associated with an increased risk of gastric adenocarcinoma and H. pylori is now classified as a type Ⅰ human carcinogen; furthermore, a causative relationship between the presence of H. pylori and the occurrence of mucosa-associated lymphiod tissue (MALT) lymphoma has been suggested. H. pylori adheres to the epithelial cell surface of the gastric mucosa. Only gastric-type epithelium is colonized, and the organism preferentially attaches at or near intercellular junctions. Like other bacteia, the binding is one of the first steps in the process by which H. pylori can bring on gastrtis, gastric ulcers, even gastric carcinoma. NeuAcLac, sulfatide, and Lewis b (Leb) have been identified as receptors on host cells. The fact suggests a complex binding mechnisam of H. pylori. In addition to the carbohydrates-mediated binding, it also has been known a number of carbohydrates on host cells are receptors of bacterial toxins,and carbohydrates on bacterial cells can serve as toxins. Lipopolysaccharide (LPS) is well known as an endotoxin of Gram-negative bacteria, but H. pylori LPS has low endotoxic activity, induces a low immunological response, and has been implicated in a variety of biological interactions. Currently, LPS has been reported to induce the inducible nitric oxide synthase (iNOS) expression and autoimmunity. The structure of H. pylori LPS O-side chain has been elucidated as Lewis x or Lewis y which is able to induce autoimmunity. To treat H. pylori infection, H2-receptor antagonist triple therapies and quadruple therapies consisting of omeprazole and traditional bismuth triple therapy have been proved effective. Using these therapies, success rates of treatments were 78%-98%. However, these treatments are not well tolerated by some patients with a significant recurrence rate. Furthermore, H. pylori has been observed to be resistant to fluroquinones, nitroimidazoles, macrolides and tetracycline.Conclusions Studies on the roles of carbohydrates in H. pylori infection provide us with some clues to the H. pylori infection itself and to the development of carbohydrate-based drugs. Carbohydrate-mediated adherence is an important focus of carbohydrate drug design. The free oligosaccharides or analogues can serve as antiadhesive drug which is able to block binding sites on bacteria and thereby prevent it from gaining a foothold. Another approach against infectious diseases is the development of polysaccharide vaccines.

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作者单位 Department of Enzymology, Institute of Microbiology, Academia Sinica, Beijing 100080, China [1]
分类号 R5
发布时间 2006-01-12
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