Structural Analysis of an Unusual Bioactive N-Acylated Lipo-Oligosaccharide LOS-IV in Mycobacterium marinum
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- 作者：Yoann Rombouts ; Elisabeth Elass ; Christophe Biot ; Emmanuel Maes ; Bernadette Coddeville ; Adeline Burguire ; Caroline Tokarski ; Eric Buisine ; Xavier Trivelli ; Laurent Kremer ; Yann Gurardel
- 刊名：Journal of the American Chemical Society
- 出版年：2010
- 出版时间：November 17, 2010
- 年：2010
- 卷：132
- 期：45
- 页码：16073-16084
- 全文大小：452K
- 年卷期：v.132,no.45(November 17, 2010)
- ISSN：1520-5126
文摘
Although lipo-oligosaccharides (LOSs) are recognized as major parietal components in many mycobacterial species, their involvement in the host−pathogen interactions have been scarcely documented. In particular, the biological implications arising from the high degree of structural species-specificity of these glycolipids remain largely unknown. Growing recognition of the Mycobacterium marinum−Danio rerio as a specific host−pathogen model devoted to the study of the physiopathology of mycobacterial infections prompted us to elucidate the structure-to-function relationships of the elusive end-product, LOS-IV, of the LOS biosynthetic pathway in M. marinum. Combination of physicochemical and molecular modeling methods established that LOS-IV resulted from the differential transfer on the caryophyllose-containing LOS-III of a family of very unusual N-acylated monosaccharides, naturally present as different diastereoisomers. In agreement with the partial loss of pathogenecity previously reported in a LOS-IV-deficient M. marinum mutant, we demonstrated that this terminal monosaccharide conferred to LOS-IV important biological functions, including macrophage activating properties.