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黏膜病原体的脂寡糖(LOS):LOS的分子模拟与宿主修饰

Lipo-oligosaccharides (LOS) of mucosal pathogens: molecular mimicry and host-modification of LOS.

作者信息

Mandrell R E, Apicella M A

机构信息

Division of Infectious Diseases, San Francisco General Hospital, University of California.

出版信息

Immunobiology. 1993 Apr;187(3-5):382-402. doi: 10.1016/S0171-2985(11)80352-9.

Abstract

Immunochemical studies of the lipo-oligosaccharides (LOS) of the Gram-negative bacteria Neisseria gonorrhoeae and Neisseria meningitidis have revealed some interesting structural characteristics of these LOS that might relate to their roles during pathogenesis. The carbohydrate moieties of the LOS of pathogenic Neisseria mimic carbohydrates present in glycosphingolipids of human cells. Firstly, an LOS component present among a number of Neisseria species is antigenically and/or chemically identical to lactoneoseries glycosphingolipids present in human cells. The lactoneoseries LOS becomes sialylated on Neisseria gonorrhoeae when they are grown in the presence of cytidine 5'-monophospho-N-acetyl-neuraminic acid (CMP-NANA), the nucleotide sugar for sialic acid. Examination of gonococci present in exudates from males with natural infection indicates that sialylation also occurs in vivo. The mechanism for this process apparently involves a bacterial sialyltransferase scavenging available host CMP-NANA ("host-modification" of LOS) and transferring the sialic acid to the lactoneoserieslike LOS. Strains of N. meningitidis and Haemophilus influenzae also express similarly sialylated LOS suggesting that this is a common mechanism of pathogenesis among these bacteria. Additional examples of LOS that mimic other glycosphingolipid series have been identified also and the fact that multiple series can be expressed in a single population of gonococci suggests that a diverse set of LOS can be presented to the host during infection. It is possible that this diverse set of LOS serve different functions for the bacteria in various hosts and/or environments during infection.

摘要

对革兰氏阴性菌淋病奈瑟菌和脑膜炎奈瑟菌的脂寡糖(LOS)进行的免疫化学研究揭示了这些LOS的一些有趣结构特征,这些特征可能与它们在发病机制中的作用有关。致病性奈瑟菌的LOS的碳水化合物部分模仿了人类细胞糖鞘脂中存在的碳水化合物。首先,许多奈瑟菌物种中存在的一种LOS成分在抗原性和/或化学性质上与人类细胞中存在的乳糖神经酰胺系列糖鞘脂相同。当淋病奈瑟菌在胞苷5'-单磷酸-N-乙酰神经氨酸(CMP-NANA,神经氨酸的核苷酸糖)存在的情况下生长时,乳糖神经酰胺系列LOS会被唾液酸化。对自然感染男性渗出物中存在的淋球菌的检查表明,唾液酸化在体内也会发生。这个过程的机制显然涉及一种细菌唾液酸转移酶清除可用的宿主CMP-NANA(LOS的“宿主修饰”),并将唾液酸转移到类似乳糖神经酰胺系列的LOS上。脑膜炎奈瑟菌和流感嗜血杆菌的菌株也表达类似唾液酸化的LOS,这表明这是这些细菌发病机制的一种常见机制。还发现了其他模仿其他糖鞘脂系列的LOS例子,并且在单个淋球菌群体中可以表达多个系列这一事实表明,在感染期间可以向宿主呈现多种不同的LOS。在感染过程中,这种多样的LOS可能在不同宿主和/或环境中为细菌发挥不同的功能。

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