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Cell-specific targeting by Clostridium perfringens β-toxin unraveled: the role of CD31 as the toxin receptor

Julia Bruggisser, Basma Tarek, Marianne Wyder, Guillaume Witz, Gaby Enzmann, Urban Deutsch, Britta Engelhardt, Horst Posthaus
doi: https://doi.org/10.1101/787242
Julia Bruggisser
Institute of Animal Pathology, Department of Infectious Diseases and Pathobiology, Vetsuisse-Faculty, University of Bern, Switzerland
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Basma Tarek
Institute of Animal Pathology, Department of Infectious Diseases and Pathobiology, Vetsuisse-Faculty, University of Bern, Switzerland
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Marianne Wyder
Institute of Animal Pathology, Department of Infectious Diseases and Pathobiology, Vetsuisse-Faculty, University of Bern, Switzerland
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Guillaume Witz
Science IT support, Mathematical Institute, University of Bern, Switzerland
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Gaby Enzmann
Theodor Kocher Institute, University of Bern, Switzerland
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Urban Deutsch
Theodor Kocher Institute, University of Bern, Switzerland
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Britta Engelhardt
Theodor Kocher Institute, University of Bern, Switzerland
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Horst Posthaus
Institute of Animal Pathology, Department of Infectious Diseases and Pathobiology, Vetsuisse-Faculty, University of Bern, SwitzerlandCOMPATH, Vetsuisse-Faculty & Faculty of Medicine, University of Bern, Switzerland
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  • For correspondence: horst.posthaus@vetsuisse.unibe.ch
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SUMMARY

Clostridium perfringens β-toxin (CPB) is a highly active hemolysin β-pore forming toxin and the essential virulence factor for a severe, necro-hemorrhagic enteritis in animals and humans. In vivo and in vitro it exerts a remarkable cell type specificity towards endothelial cells, platelets and some leucocytic cell lines. The target cell specificity of CPB is, however, poorly understood and a receptor explaining this selective toxicity has not been identified. This has hampered further research into the pathogenesis of C. perfringens type C induced enteritis. Here we identify Platelet Endothelial Cell Adhesion Molecule-1 (CD31 or PECAM-1) as the specific membrane receptor for CPB on endothelial cells. CD31 expression is essential for CPB toxicity in endothelial cells and lethality in mice and sufficient to render previously resistant cells highly susceptible to the toxin. We further demonstrate, that the extracellular membrane proximal Ig6 domain of CD31 is required for the interaction with CPB and that expression of CD31 corresponds with the specificity of the toxin towards cultured cell lines. Our results thus provide an explanation for the cell type specificity of CPB and can be linked to the characteristic lesions observed a devastating enteric disease in animals and humans.

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  • http://doi.org/10.5281/zenodo.3463302

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Posted October 01, 2019.
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Cell-specific targeting by Clostridium perfringens β-toxin unraveled: the role of CD31 as the toxin receptor
Julia Bruggisser, Basma Tarek, Marianne Wyder, Guillaume Witz, Gaby Enzmann, Urban Deutsch, Britta Engelhardt, Horst Posthaus
bioRxiv 787242; doi: https://doi.org/10.1101/787242
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Cell-specific targeting by Clostridium perfringens β-toxin unraveled: the role of CD31 as the toxin receptor
Julia Bruggisser, Basma Tarek, Marianne Wyder, Guillaume Witz, Gaby Enzmann, Urban Deutsch, Britta Engelhardt, Horst Posthaus
bioRxiv 787242; doi: https://doi.org/10.1101/787242

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