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Opportunities and Challenges of Bacterial Glycosylation for the Development of Novel Antibacterial Strategies
Frontiers in Microbiology ( IF 4.0 ) Pub Date : 2021-09-24 , DOI: 10.3389/fmicb.2021.745702
Liubov Yakovlieva 1 , Julius A Fülleborn 1 , Marthe T C Walvoort 1
Affiliation  

Glycosylation is a ubiquitous process that is universally conserved in nature. The various products of glycosylation, such as polysaccharides, glycoproteins, and glycolipids, perform a myriad of intra- and extracellular functions. The multitude of roles performed by these molecules is reflected in the significant diversity of glycan structures and linkages found in eukaryotes and prokaryotes. Importantly, glycosylation is highly relevant for the virulence of many bacterial pathogens. Various surface-associated glycoconjugates have been identified in bacteria that promote infectious behavior and survival in the host through motility, adhesion, molecular mimicry, and immune system manipulation. Interestingly, bacterial glycosylation systems that produce these virulence factors frequently feature rare monosaccharides and unusual glycosylation mechanisms. Owing to their marked difference from human glycosylation, bacterial glycosylation systems constitute promising antibacterial targets. With the rise of antibiotic resistance and depletion of the antibiotic pipeline, novel drug targets are urgently needed. Bacteria-specific glycosylation systems are especially promising for antivirulence therapies that do not eliminate a bacterial population, but rather alleviate its pathogenesis. In this review, we describe a selection of unique glycosylation systems in bacterial pathogens and their role in bacterial homeostasis and infection, with a focus on virulence factors. In addition, recent advances to inhibit the enzymes involved in these glycosylation systems and target the bacterial glycan structures directly will be highlighted. Together, this review provides an overview of the current status and promise for the future of using bacterial glycosylation to develop novel antibacterial strategies.



中文翻译:

细菌糖基化对开发新型抗菌策略的机遇和挑战

糖基化是一种普遍存在的过程,在自然界中普遍保守。糖基化的各种产物,如多糖、糖蛋白和糖脂,在细胞内和细胞外发挥着无数的功能。这些分子发挥的多种作用反映在真核生物和原核生物中发现的聚糖结构和连接的显着多样性上。重要的是,糖基化与许多细菌病原体的毒力高度相关。已经在细菌中鉴定出多种表面相关的糖缀合物,它们通过运动、粘附、分子模拟和免疫系统操作促进宿主的感染行为和存活。有趣的是,产生这些毒力因子的细菌糖基化系统通常具有罕见的单糖和不寻常的糖基化机制。由于它们与人类糖基化的显着差异,细菌糖基化系统构成了有希望的抗菌靶点。随着抗生素耐药性的上升和抗生素管道的枯竭,迫切需要新的药物靶点。细菌特异性糖基化系统对于不消除细菌种群而是减轻其发病机制的抗毒力疗法尤其有希望。在这篇综述中,我们描述了细菌病原体中一系列独特的糖基化系统及其在细菌稳态和感染中的作用,重点是毒力因子。此外,将强调抑制参与这些糖基化系统的酶和直接靶向细菌聚糖结构的最新进展。总之,本综述概述了使用细菌糖基化开发新型抗菌策略的现状和前景。

更新日期:2021-09-24
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