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. Epub 2020 Jun 3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacterial Toxins / metabolism*
  • Cell Line
  • Cells, Cultured
  • Clostridium Infections / microbiology
  • Clostridium perfringens / pathogenicity*
  • Clostridium perfringens / physiology
  • Endothelial Cells / metabolism*
  • Endothelial Cells / microbiology*
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Platelet Endothelial Cell Adhesion Molecule-1 / genetics
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism*
  • Protein Interaction Domains and Motifs
  • Swine
  • Virulence Factors / metabolism


  • Bacterial Toxins
  • CPB protein, Clostridium perfringens
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Virulence Factors