The Lipopolysaccharide from Capnocytophaga canimorsus Reveals an Unexpected Role of the Core-Oligosaccharide in MD-2 Binding

PLoS Pathogens

Simon Ittig¹  Pablo Manfredi¹  Guy R. Cornelis¹  Buko Lindner²  Ulrich Zähringer²  Matteo dal Peraro³  Marco Stenta³  Yuriy A. Knirel⁴  Evelina Zdorovenko⁴ 

[1] Biozentrum der Universität Basel, Basel, Switzerland;Division of Immunochemistry, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany;Laboratory for Biomolecular Modeling, Institute of Bioengineering, School of Life Sciences, Swiss Federal Institute of Technology, EPF Lausanne, Switzerland;N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia

关键词: Lipids;    Capnocytophaga canimorsus;    Lipid structure;    Phosphates;    Lipid analysis;    High performance liquid chromatography;    NMR spectroscopy;    Macrophages;   

DOI  :  10.1371/journal.ppat.1002667

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Capnocytophaga canimorsus is a usual member of dog's mouths flora that causes rare but dramatic human infections after dog bites. We determined the structure of C. canimorsus lipid A. The main features are that it is penta-acylated and composed of a “hybrid backbone” lacking the 4′ phosphate and having a 1 phosphoethanolamine (P-Etn) at 2-amino-2-deoxy-d-glucose (GlcN). C. canimorsus LPS was 100 fold less endotoxic than Escherichia coli LPS. Surprisingly, C. canimorsus lipid A was 20,000 fold less endotoxic than the C. canimorsus lipid A-core. This represents the first example in which the core-oligosaccharide dramatically increases endotoxicity of a low endotoxic lipid A. The binding to human myeloid differentiation factor 2 (MD-2) was dramatically increased upon presence of the LPS core on the lipid A, explaining the difference in endotoxicity. Interaction of MD-2, cluster of differentiation antigen 14 (CD14) or LPS-binding protein (LBP) with the negative charge in the 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) of the core might be needed to form the MD-2 – lipid A complex in case the 4′ phosphate is not present.

【 授权许可】

CC BY