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学术报告_Exploiting genomics in the structural analysis of short-chain lipopolysaccharides

作者:编辑: 时间:2010-11-02 点击量:

时间:2010114(星期四)上午9:00

地点:生命科学与技术学院(东11楼)二楼会议室

报告人:Professor Elke K.H. Schweda

Karolinska Institutet, Clinical Research Centre, Sweden

摘要:

     The structural determination of bacterial lipopolysaccharides (LPS) remains a major challenge due to extensive heterogeneity that certain species exhibit. For more than a decade we have focussed on applying a combination of genomics and advanced MS based techniques to profile LPS oligosaccharide structural diversity in non-typeable Haemophilus influenzae (NTHi) clinical isolates. This approach has not only facilitated LPS structural elucidation but also shed light on the genetic basis of LPS oligosaccharide assembly. It is now well known that the short-chain LPS (often referred to as lipooligosaccharide) elaborated by H. influenzae comprises a conserved glucose-substituted  triheptosyl inner-core moiety, L--D-Hepp-(1®2)-[PEtn®6] -L--D-Hepp-(1®3)-[-D-Glcp-(1-4)]-L--D-Hepp linked to lipid A via a Kdo 4-phosphate. This inner-core unit provides the template for attachment of oligosaccharide- and non carbohydrate substituents including phosphocholine, phosphoethanolamine, acetate and glycine. Many of the genes involved in expression of these structural features have now been identified. Genomic information has been instrumental in helping us to identify minor glycoform populations that may be important in pathogenesis of NTHi, a major cause of otitis media in children. In combination with liquid chromatography multiple step tandem mass spectrometry (LC-ESI-MSn) and capillary electrophoresis mass spectrometry (CE-ESI-MS) we have employed this genomic information to profile NTHi LPS glycoform populations from both in vitro and in vivo sources.

 



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