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Facing glycosphingolipid–Shiga toxin interaction: dire straits for endothelial cells of the human vasculature

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Abstract

The two major Shiga toxin (Stx) types, Stx1 and Stx2, produced by enterohemorrhagic Escherichia coli (EHEC) in particular injure renal and cerebral microvascular endothelial cells after transfer from the human intestine into the circulation. Stxs are AB5 toxins composed of an enzymatically active A subunit and the pentameric B subunit, which preferentially binds to the glycosphingolipid globotriaosylceramide (Gb3Cer/CD77). This review summarizes the current knowledge on Stx-caused cellular injury and the structural diversity of Stx receptors as well as the initial molecular interaction of Stxs with the human endothelium of different vascular beds. The varying lipoforms of Stx receptors and their spatial organization in lipid rafts suggest a central role in different modes of receptor-mediated endocytosis and intracellular destiny of the toxins. The design and development of tailored Stx neutralizers targeting the oligosaccharide–toxin recognition event has become a very real prospect to ameliorate or prevent life-threatening renal and neurological complications.

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Acknowledgments

J.M. is grateful for continuous support of his work by grants from the Deutsche Forschungsgemeinschaft (DFG), MU845/4-1 and MU845/4-2, the GRK 1409/1 and 1409/2 and grants from the Interdisciplinary Center of Clinical Research (IZKF) Münster, project no. Müth2/028/10 as well as the National Research Platform for Zoonoses funded by the German Federal Ministry of Education and Research (BMBF, project 01KI1106). H.K. gratefully acknowledges financial support of the DFG, KA 717/5-1, grants from the IZKF Münster, project no. Me2/021/12, and the National Research Platform for Zoonoses funded by the BMBF (project 01KI1012B). B.K. acknowledges financial support by the BMBF within the reserach focus program “Biophotonics” (FKZ 13N9270, FKZ 13N10937).

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  1. Institute for Hygiene, University of Münster, Robert-Koch-Str. 41, 48149, Münster, Germany

    Andreas Bauwens, Josefine Betz, Iris Meisen, Helge Karch & Johannes Müthing

  2. Interdisciplinary Center for Clinical Research, University of Münster, Domagkstr. 3, 48149, Münster, Germany

    Iris Meisen & Johannes Müthing

  3. Center for Biomedical Optics and Photonics, University of Münster, Robert-Koch-Str. 45, 48149, Münster, Germany

    Björn Kemper

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  1. Andreas Bauwens
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  2. Josefine Betz
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Correspondence to Johannes Müthing.

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Bauwens, A., Betz, J., Meisen, I. et al. Facing glycosphingolipid–Shiga toxin interaction: dire straits for endothelial cells of the human vasculature. Cell. Mol. Life Sci. 70, 425–457 (2013). https://doi.org/10.1007/s00018-012-1060-z

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