A commensal adhesin enhances E. coli retention by mucin, while mucin desulfation by mucin-foraging bacteria enhances its transmigration through the mucus barrier
A commensal adhesin enhances E. coli retention by mucin, while mucin desulfation by mucin-foraging bacteria enhances its transmigration through the mucus barrier
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DOI：
10.1101/126672
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发表时间：
2017-04
期刊：
影响因子：
--
通讯作者：
Fitua Al-Saedi;D. Vaz;D. Stones;A. Krachler
中科院分区：
文献类型：
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作者：
Fitua Al-Saedi;D. Vaz;D. Stones;A. Krachler
细菌对宿主受体的粘附是细菌定殖的早期和重要步骤，粘附-受体相互作用的性质决定了细菌的定位，从而决定了这些相互作用的结果。在这里，我们确定了宿主受体的多价粘附分子从肠道寄生虫E。coliHS（MAMHS），它含有一系列的7个哺乳动物细胞进入（MCE）结构域。MAMHS粘附素通过识别共享的3-O-磺基-半乳糖基部分与一系列宿主受体相互作用。该官能团也存在于粘蛋白中，粘蛋白是肠粘液层的组分，因此是大肠杆菌的主要粘附靶点之一。杆菌粘蛋白凝胶阻碍E.大肠杆菌作为一个物理屏障，和屏障效应增强粘蛋白和MAMHS之间的特定相互作用，硫酸化依赖的方式。纯硫酸酯酶或产生硫酸酯酶的多形拟杆菌对粘蛋白的脱硫作用降低了E.通过与表面定位的硫酸化脂质和蛋白质受体的相互作用，将大肠杆菌粘附到粘蛋白上，并增加细菌对上皮表面的附着。总之，我们的结果表明，E。大肠杆菌粘附素MAMHS促进粘蛋白对肠上皮细胞的保留，并表明栖息在同一生态位的粘蛋白觅食细菌分泌的硫酸酯酶的量，如B。tetaiotaomicron，可能会影响粘液屏障的能力，以保持大肠杆菌。杆菌
Bacterial adhesion to host receptors is an early and essential step in bacterial colonization, and the nature of adhesion-receptor interactions determines bacterial localization and thus the outcome of these interactions. Here, we determine the host receptors for the Multivalent Adhesion Molecule from the gut commensal E. coli HS (MAMHS), which contains an array of seven mammalian cell entry (MCE) domains. The MAMHS adhesin interacts with a range of host receptors, through recognition of a shared 3-O-sulfo-galactosyl moiety. This functional group is also found in mucin, a component of the intestinal mucus layer and thus one of the prime adherence targets for commensal E. coli. Mucin gels impede the motility of E. coli by acting as a physical barrier, and the barrier effect is enhanced by specific interactions between mucin and MAMHS in a sulfation-dependent manner. Desulfation of mucin by pure sulfatase or the sulfatase-producing commensal Bacteroides thetaiotaomicron decreases binding of E. coli to mucin and increases attachment of bacteria to the epithelial surface, through interactions with surface-localized sulfated lipid and protein receptors. Together, our results demonstrate that the E. coli adhesin MAMHS facilitates retention of a gut commensal by mucin, and suggest that the amount of sulfatase secreted by mucin-foraging bacteria inhabiting the same niche, such as B. thetaiotaomicron, may affect the capacity of the mucus barrier to retain commensal E. coli.