Two complementary α-fucosidases from Streptococcus pneumoniae promote complete degradation of host-derived carbohydrate antigens
Two complementary α-fucosidases from Streptococcus pneumoniae promote complete degradation of host-derived carbohydrate antigens
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DOI：
10.1074/jbc.ra119.009368
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发表时间：
2019-08-23
影响因子：
4.8
通讯作者：
Boraston, Alisdair B.
中科院分区：
文献类型：
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作者：
Hobbs, Joanne K.;Pluvinage, Benjamin;Boraston, Alisdair B.
机会性细菌病原体肺炎链球菌与其人类宿主之间相互作用的一个重要方面是其收获宿主聚糖的能力。肺炎球菌可以降解多种复杂的聚糖，包括N-和o -连接的聚糖、糖胺聚糖和碳水化合物抗原，这种能力与肺炎链球菌的毒力密切相关。虽然已知肺炎链球菌使用一种复杂的酶机制来攻击人类糖原，但它如何处理主要是组织血型抗原的浓缩糖原，在很大程度上是未知的。在这里，我们确定了两种肺炎球菌酶，SpGH29(C)和SpGH95(C)，分别针对α -(1 -> 3/4)和α -(1 -> 2)聚焦键。X射线晶体学研究结合功能分析表明，SpGH29(C)对Lewis(A)和Lewis(X)抗原基序具有特异性，而SpGH95(C)对H(O)抗原基序具有特异性。总之，这些酶能够以互补的方式去聚焦Lewis(Y)和Lewis(B)抗原。多糖降解级联的体外重建表明，这些酶的单独或联合活性暴露了潜在的多糖结构，促进了糖的完全解构，否则糖就会对肺炎球菌酶产生抗性。这些实验扩大了我们对肺炎链球菌处理宿主聚糖的广泛能力以及α -聚焦酶在其中可能发挥的作用的理解。总的来说，考虑到在肺炎球菌毒力中启动聚糖分解的酶的重要性，如神经氨酸酶NanA和甘露糖苷酶SpGH92，我们预计在这里确定的α -聚焦酶将是开发更精细的肺炎链球菌-宿主相互作用模型的重要因素。
An important aspect of the interaction between the opportunistic bacterial pathogen Streptococcus pneumoniae and its human host is its ability to harvest host glycans. The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae. Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown. Here, we identified two pneumococcal enzymes, SpGH29(C) and SpGH95(C), that target alpha-(1 -> 3/4) and alpha-(1 -> 2) fucosidic linkages, respectively. X-ray crystallography studies combined with functional assays revealed that SpGH29(C) is specific for the Lewis(A) and Lewis(X) antigen motifs and that SpGH95(C) is specific for the H(O)-antigen motif. Together, these enzymes could defucosylate Lewis(Y) and Lewis(B) antigens in a complementary fashion. In vitro reconstruction of glycan degradation cascades disclosed that the individual or combined activities of these enzymes expose the underlying glycan structure, promoting the complete deconstruction of a glycan that would otherwise be resistant to pneumococcal enzymes. These experiments expand our understanding of the extensive capacity of S. pneumoniae to process host glycans and the likely roles of alpha-fucosidases in this. Overall, given the importance of enzymes that initiate glycan breakdown in pneumococcal virulence, such as the neuraminidase NanA and the mannosidase SpGH92, we anticipate that the alpha-fucosidases identified here will be important factors in developing more refined models of the S. pneumoniae-host interaction.