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结构鉴定脂质-α:寡糖和多糖代谢中涉及的糖脂在无乳链球菌(B 组链球菌)。

Structural Identification of Lipid-α: A Glycosyl Lipid Involved in Oligo- And Polysaccharides Metabolism in Streptococcus agalactiae (Group B Streptococcus).

机构信息

Department of Medicine, Boston University School of Medicine, Boston, MA, USA.

Glyde Bio, Inc., Cambridge, MA, USA.

出版信息

Curr Microbiol. 2022 Dec 2;80(1):16. doi: 10.1007/s00284-022-03117-8.

DOI:10.1007/s00284-022-03117-8
PMID:36459236
Abstract

Streptococcus agalactiae (group B Streptococcus, GBS) is a gram-positive bacterium that is an asymptomatic colonizer commonly found in the gastrointestinal and genitourinary tract of healthy adults. GBS is also the most common cause of life-threatening bacterial infections in newborns and is emerging as a pathogen in immunocompromised and diabetic adults. The GBS cell wall and covalently linked capsular polysaccharides (CPS) are vital to the protection of the bacterial cell and act as virulence factors. GBS-CPS have been successfully used to produce conjugate vaccines for all currently identified GBS serotypes. However, the mechanisms of biosynthesis and assembly of CPS and the other cell wall components remain poorly defined due to their complex surface structures. In this biosynthetic study of the GBS cell wall-CPS complex, glycolipids with varying lengths of glycosyl-chains were discovered. Among those, one of the smallest glycolipids (named GBS Lipid-α) was structurally characterized. Lipid-α is involved in GBS saccharide metabolism and presumably acts as a glycosyl acceptor to elongate the glycosyl chain. GBS Lipid-α was determined to be a 3-monosaccharide 1,2 acyl glycerol with a molecular mass in the range of m/z = 724-808. GBS Lipid-α is highly heterogenic with various acyl groups and glycosyl moieties. This knowledge will pave the way for future studies to elucidate the entire metabolic pathway and genes involved. The Lipid-α pathway may also exist in other bacterial species and has the potential to be a biomarker for future drug development.

摘要

无乳链球菌(B 群链球菌,GBS)是一种革兰氏阳性细菌,通常作为无症状定植菌存在于健康成人的胃肠道和泌尿生殖道中。GBS 也是导致新生儿致命性细菌感染的最常见原因,并且在免疫功能低下和糖尿病成人中作为病原体出现。GBS 细胞壁和共价连接的荚膜多糖(CPS)对于保护细菌细胞至关重要,并且作为毒力因子发挥作用。GBS-CPS 已成功用于生产针对所有现有 GBS 血清型的结合疫苗。然而,由于其复杂的表面结构,CPS 和其他细胞壁成分的生物合成和组装机制仍未得到充分定义。在这项 GBS 细胞壁-CPS 复合物的生物合成研究中,发现了具有不同糖基链长度的糖脂。在这些糖脂中,有一种最小的糖脂(命名为 GBS Lipid-α)的结构特征被确定。Lipid-α 参与 GBS 糖代谢,推测作为糖基受体来延长糖基链。GBS Lipid-α 被确定为具有 3 个单糖 1,2 酰基甘油,分子量范围为 m/z=724-808。GBS Lipid-α 高度异质,具有各种酰基和糖基部分。这一知识将为未来阐明整个代谢途径和相关基因的研究铺平道路。脂质-α 途径可能也存在于其他细菌物种中,并有潜力成为未来药物开发的生物标志物。

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