2. Academic Validation
  3. CD31 (PECAM-1) Serves as the Endothelial Cell-Specific Receptor of Clostridium perfringens β-Toxin

CD31 (PECAM-1) Serves as the Endothelial Cell-Specific Receptor of Clostridium perfringens β-Toxin

  • Cell Host Microbe. 2020 Jul 8;28(1):69-78.e6. doi: 10.1016/j.chom.2020.05.003.
Julia Bruggisser 1,  Basma Tarek 1,  Marianne Wyder 1,  Philipp Müller 2,  Christoph von Ballmoos 2,  Guillaume Witz 3,  Gaby Enzmann 4,  Urban Deutsch 4,  Britta Engelhardt 4,  Horst Posthaus 5
Affiliations

Affiliations

  • 1 Institute of Animal Pathology, Department of Infectious Diseases and Pathobiology, Vetsuisse-Faculty, University of Bern, 3012 Bern, Switzerland.
  • 2 Department of Chemistry and Biochemistry, Faculty of Sciences, University of Bern, 3012 Bern, Switzerland.
  • 3 Microscopy Imaging Center (MIC) University of Bern, 3012 Bern, Switzerland; Science IT Support (ScITS), Mathematical Institute, University of Bern, Bern, Switzerland.
  • 4 Theodor Kocher Institute, Faculty of Medicine, University of Bern, 3012 Bern, Switzerland.
  • 5 Institute of Animal Pathology, Department of Infectious Diseases and Pathobiology, Vetsuisse-Faculty, University of Bern, 3012 Bern, Switzerland; COMPATH, Vetsuisse-Faculty & Faculty of Medicine, University of Bern, 3012 Bern, Switzerland. Electronic address: [email protected].
PMID: 32497498 DOI: 10.1016/j.chom.2020.05.003
Abstract

Clostridium perfringens β-toxin (CPB) is a highly active β-pore-forming toxin (β-PFT) and the essential virulence factor for fatal, necro-hemorrhagic enteritis in Animals and humans. The molecular mechanisms involved in CPB's action on its target, the endothelium of small intestinal vessels, are poorly understood. 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 corresponds with the cell-type specificity of CPB, and it is essential for toxicity in cultured cells and mice. Ectopic CD31 expression renders resistant cells and liposomes susceptible to CPB-induced membrane damage. Moreover, the extracellular Ig6 domain of mouse, human, and porcine CD31 is essential for the interaction with CPB. Hence, our results explain the cell-type specificity of CPB in vitro and in the natural disease caused by C. perfringens type C.

Keywords

CD31; Clostridium perfringens type C; PECAM-1; endothelial cells; membrane proteins; pore-forming toxins; toxin receptors; β-toxin.

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