摘要
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.
基金
This work was financially supported by the National Key Research and Development Program of China(2021YFA0909400)
the National Natural Science Foundation of China(22105123,22305152)
the Shanghai Rising-Star Program(23QA1408600),the Explorer Program of the Science and Technology Commission of Shanghai Municipality(21TS1400400)
the Interdisciplinary Program of Shanghai Jiao Tong University(YG2021QN35),the Innovative Research Team of High-Level Local Universities in Shanghai(SHSMU-ZDCX20210900)
the Foundation of National Infrastructures for Translational Medicine(Shanghai)(TMSK-2021-119)
the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(20181704).