School of Biosciences, University of Sheffield, Sheffield, UK.
School of Biosciences, University of Sheffield, Sheffield, UK.
Carbohydr Polym. 2025 Jan 1;347:122686. doi: 10.1016/j.carbpol.2024.122686. Epub 2024 Aug 30.
Streptococci, Lactococci and Enterococci all produce L-rhamnose-containing cell wall polysaccharides which define Lancefield serotypes and represent promising candidates for the design of glycoconjugate vaccines. The L-rhamnose containing Enterococcal Polysaccharide Antigen (EPA), produced by the opportunistic pathogen Enterococcus faecalis, plays a critical role in normal growth, division, biofilm formation, antimicrobial resistance, phage susceptibility, and innate immune evasion. Despite the critical role of this polymer in E. faecalis physiology and host-pathogen interactions, little information is available on its structure and biosynthesis. Here, using an NMR approach, we elucidate the structure of EPA and propose a model for biosynthesis. We report the structure of the EPA-peptidoglycan linkage unit and reveal an unprecedented complexity of the EPA rhamnose backbone and decoration subunits. Finally, we explore the impact of several EPA structural modifications on innate immune evasion and recognition by bacteriophages. This work represents a first step towards the functional characterisation of EPA and the rational design of therapeutic strategies against a group of important pathogens.
链球菌、乳球菌和肠球菌都产生含有 L-鼠李糖的细胞壁多糖，这些多糖定义了 Lancefield 血清型，是糖缀合物疫苗设计的有前途的候选物。机会性病原体粪肠球菌产生的含有 L-鼠李糖的肠球菌多糖抗原（EPA）在正常生长、分裂、生物膜形成、抗菌药物耐药性、噬菌体敏感性和固有免疫逃避中发挥着关键作用。尽管这种聚合物在粪肠球菌生理学和宿主-病原体相互作用中起着关键作用，但关于其结构和生物合成的信息却很少。在这里，我们使用 NMR 方法阐明了 EPA 的结构，并提出了生物合成模型。我们报告了 EPA-肽聚糖连接单元的结构，并揭示了 EPA 鼠李糖主链和修饰亚基的空前复杂性。最后，我们探讨了 EPA 结构修饰对固有免疫逃避和噬菌体识别的影响。这项工作代表了对 EPA 功能特性进行功能表征以及针对一组重要病原体的合理治疗策略设计的第一步。
