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Published on: October 31, 2017

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Clostridium perfringens α-toxin specifically induces endothelial cell death by promoting ceramide-mediated apoptosis

Masaya Takehara1, Hiroto Bandou1, Keiko Kobayashi1

  • 1Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima, 770-8514, Japan.

Anaerobe
|August 24, 2020
PubMed

Insights

Clostridium perfringens alpha-toxin causes gas gangrene by killing endothelial cells, leading to severe muscle death. This study reveals the toxin

Area of Science:

  • Microbiology
  • Pathogenesis
  • Toxicology

Background:

  • Clostridium perfringens type A causes gas gangrene, a severe condition characterized by myonecrosis.
  • Alpha-toxin (CPA) is a key virulence factor in C. perfringens pathogenesis, but its precise mechanism remains unclear.

Purpose of the Study:

  • To elucidate the mechanism by which alpha-toxin contributes to the pathogenesis of C. perfringens-induced gas gangrene.
  • To investigate the effect of alpha-toxin on endothelial cells and muscle cells.

Main Methods:

  • In vivo analysis of CD31+ endothelial cell counts in infected muscle tissue.
  • In vitro experiments assessing the toxicity of alpha-toxin on human umbilical vein endothelial cells (HUVECs) and C2C12 murine muscle cells.
  • Investigation of the role of ceramide in alpha-toxin-induced cell death.

Main Results:

  • Alpha-toxin significantly reduces CD31+ endothelial cell counts in C. perfringens-infected muscles.
  • In vitro, alpha-toxin preferentially induces rapid apoptosis in HUVECs compared to C2C12 cells.
  • Alpha-toxin-induced HUVEC death is mediated by increased ceramide levels, with differential sensitivity between cell types.

Conclusions:

  • Alpha-toxin directly induces endothelial cell death, contributing to severe myonecrosis in gas gangrene.
  • The differential sensitivity to ceramide may explain the toxin's specific targeting of endothelial cells.
  • Targeting alpha-toxin or its downstream effects could be a therapeutic strategy for C. perfringens infections.
Keywords:
ApoptosisClostridium perfringens α-toxinEndothelial cell death

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