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Top-down Mass Spectrometric Analysis of a Lipooligosaccharide from the Human Commensal Bacteroides fragilis

Yang, T.; Daugherty, J.; Kasper, D. L.

2024-04-14 biochemistry
10.1101/2024.04.13.589361 bioRxiv
Show abstract

Lipopolysaccharides (LPS) and lipooligosaccharides (LOS) are ubiquitous structures found on the outer membrane of gram-negative bacteria. Bacteroides fragilis, is a gram-negative anaerobe commonly inhabiting the human colon. The LOS of this organism is known to trigger a type I interferon response in dendritic cells. However, detailed structural analysis of this LOS has been largely elusive. Using top-down mass spectrometry, we have unraveled the comprehensive fine structure of B. fragilis LOS. Our analysis reveals that this LOS has a poly-galactose-rhamnose-KDO-lipid A architecture, which can be modified by hexuronic acid and ethanolamine via phosphodiester linkages. The lipid moiety typically includes three to five acyl chains of varying length on a glucosamine disaccharide. This investigation lays the groundwork for deeper immunological exploration of B. fragilis LOS and underscores the efficacy of top-down mass spectrometry in characterizing intact LOS/LPS structures and their modifications.

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