Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides
Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides
复制标题
DOI：
10.1038/s41589-019-0251-4
复制
发表时间：
2019-05-01
影响因子：
14.8
通讯作者：
Korotkova, Natalia
中科院分区：
文献类型：
--
作者：
Edgar, Rebecca J.;van Hensbergen, Vincent P.;Korotkova, Natalia
革兰氏阳性细菌表面的细胞壁糖共聚物是细菌生理学和感染生物学的基础。在这里，我们在两个独立的转座子文库筛选中鉴定了化脓性链球菌a组碳水化合物（GAC）生物合成簇中的gacH基因，以确定其对锌的抗性和对杀菌酶人类iia分泌的磷脂酶a的敏感性(2)。随后对GacH胞外结构域的结构和系统发育分析表明，GacH代表了另一类甘油磷酸转移酶。我们检测了GAC中磷酸甘油的存在，以及变形链球菌血清c型碳水化合物的存在，这取决于各自gacH同源物的存在。最后，对GAC的核磁共振分析证实，磷酸甘油附着在大约25%的GAC n -乙酰氨基葡萄糖侧链的C6羟基上。这种以前未被认识到的结构修饰影响宿主-病原体相互作用，并对疫苗设计产生影响。
Cell wall glycopolymers on the surface of Gram-positive bacteria are fundamental to bacterial physiology and infection biology. Here we identify gacH, a gene in the Streptococcus pyogenes group A carbohydrate (GAC) biosynthetic cluster, in two independent transposon library screens for its ability to confer resistance to zinc and susceptibility to the bactericidal enzyme human group IIA-secreted phospholipase A(2). Subsequent structural and phylogenetic analysis of the GacH extracellular domain revealed that GacH represents an alternative class of glycerol phosphate transferase. We detected the presence of glycerol phosphate in the GAC, as well as the serotype c carbohydrate from Streptococcus mutans, which depended on the presence of the respective gacH homologs. Finally, nuclear magnetic resonance analysis of GAC confirmed that glycerol phosphate is attached to approximately 25% of the GAC N-acetylglucosamine side-chains at the C6 hydroxyl group. This previously unrecognized structural modification impacts host-pathogen interaction and has implications for vaccine design.