上海交通大学刘尽尧团队报道了表面拓扑糖基化介导的细菌黏附。相关研究成果于2024年3月13日发表于国际一流学术期刊《中国化学》。

存在于细菌表面的糖部分是细菌活性的关键调节因子。精确调整表面糖部分的丰度和分布可以为控制细菌行为提供一种重要的方法，但已被证明是困难的。

该文报道了表面拓扑糖基化介导细菌与粘膜层的相互作用。通过迭代迈克尔加成和酰胺缩合反应合成了由具有不同支化的糖部分官能化的炔烃。通过铜催化的叠氮化物-炔烃环加成，得到的具有不同分支结构的化合物可以附着在用叠氮化物基团修饰的细菌表面上。作为概念验证研究，研究人员分别使用线性、双支化和四支化化合物制备了一组拓扑糖基化益生菌（TGPs）。

研究人员研究了粘蛋白和TGPs之间的相互作用，结果表明，与未修饰的细菌相比，TGPs对粘蛋白的粘附能力增强，随分枝数的增加而增加。在离体结肠粘液粘附实验中观察到类似的结合趋势，并且用四支链化合物糖基化的细菌显示出最高的结合效率。

该项工作提出了一种化学方法来调节细菌上糖部分的丰度和分布，为通过表面修饰操纵细菌行为提供了独特的重要见解。

附：英文原文

Title: Surface Topological Glycosylation-Mediated Mucoadhesion of Bacteria†

Author: Xiao Kuang, Xiaobing Liu, Ju Chen, Wenyan Lv, Mengmeng Zhang, Huan Chen, Feng Wu, Jinyao Liu

Issue&Volume: 2024-03-13

Abstract: Sugar moieties present on bacterial surface serve as pivotal regulators of bacterial activity. Precisely adjusting the abundance and distribution of surface sugar moieties can offer an important approach to manipulating bacterial behavior, but has been proven to be difficult. Herein, surface topological glycosylation is reported to mediate the interaction of bacteria with mucous layer. Alkynes functionalized by sugar moieties with different branching are synthesized through iterative Michael addition and amide condensation reactions. By a copper-catalyzed azide-alkyne cycloaddition, the resulting compounds with different branching structures can be attached onto bacterial surface that is modified with azido groups. As a proof-of-concept study, a set of topologically glycosylated probiotics (TGPs) is prepared using linear, two-branched, and tetra-branched compounds, respectively. The interaction between mucin and TGPs was studied and the results demonstrate that, compared to unmodified bacteria, TGPs exhibit an enhanced adhesive capacity to mucin, which increases with the branching numbers. Similar binding trend is observed in ex vivo colonic mucus adhesion experiments and bacteria glycosylated with tetra-branched compounds display the highest binding efficiency. This work proposes a chemical method to tune the abundance and distribution of sugar moieties on bacteria, providing unique significant insights into the manipulation of bacterial behavior through surface modification.

DOI: 10.1002/cjoc.202300713

Source: https://onlinelibrary.wiley.com/doi/full/10.1002/cjoc.202300713