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Invasion and Replication Strategies of Pathogenes
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SP A8

Structure, Biosynthesis and Function
of Glykoconjugates from Helminths



Dr. Günter Lochnit

Prof. Dr. Rudolf Geyer
Biochemisches Institut (FB 11), Justus-Liebig-Universität, Gießen



Summary

Helminth infections still belong to the most prevalent infections of humans and animals. During infection, glycoconjugates and specially those, substituted with phosphocholine (PC), play a central role. These epitopes are present on glycosphingolipids and (glyco)proteins. We concentrate on nematodes and the two model systems Ascaris suum, a pig parasitic nematode and the free living nematode Caenorhabditis elegans.

We have structurally elucidated the most complex glycosphingolipid structures of a nematode from the parasitic nematode Ascaris suum reported so far. These investigations revealed new structural motifs and reflected the enormous glycosylation potential of nematodes. Furthermore, we could - for the first time – isolate and identify a PC-modified protein from C. elegans. In the future, additional PC-modified proteins will be isolated, characterized and identified and the PC-modification should be localized and structurally elucidated.

Besides the structural analyses, investigations on the biological activities of these antigens are a major point of our interest. PC-substituted antigens are known to have immunomodulatory activities. Inhibition of lymphoid proliferation and induction of various cytokines were observed. These investigations should continue and cellular receptors of the PC-epitopes should be identified with an established photo affinity labelling method.

The biosynthesis of non-host derived structures is a promising target for the development of new anthelminthics. Several inhibitors of the choline-metabolism and glycosphingolipid biosynthesis have already revealed significant effects on the development of nematodes. To elucidate additional inhibitors, the enzymes involved in the biosynthesis of PC-epitopes should be identified by RNA interference experiments.

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