Role of P2X7 receptor in Clostridium perfringens beta-toxin-mediated cellular injury

Masahiro Nagahama1, Soshi Seike1, Hidenori Shirai1

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

Abstract

Insights

Clostridium perfringens beta-toxin induces cell death by interacting with the P2X(7) receptor. Blocking this interaction with specific antagonists prevents beta-toxin toxicity and lethality in mice, identifying P2X(7) as a therapeutic target.

Area of Science:

  • Microbiology and Immunology
  • Cell Biology
  • Toxicology

Background:

  • Clostridium perfringens beta-toxin is a pore-forming toxin implicated in necrotic enteritis and enterotoxemia.
  • Beta-toxin induces cell death through oligomer formation.
  • The P2X(7) receptor, an ATP-gated ion channel, has been identified as an interacting partner of beta-toxin.

Purpose of the Study:

  • To investigate the role of the P2X(7) receptor in beta-toxin-induced cytotoxicity.
  • To determine if P2X(7) receptor is a potential therapeutic target for C. perfringens type C infections.

Main Methods:

  • Utilized specific P2X(7) receptor inhibitors (oxidized ATP, Brilliant Blue G) and siRNA knockdown.
  • Assessed toxin-cell interaction using dot-blot assays and cellular localization studies.
  • Evaluated beta-toxin lethality in an in vivo mouse model.

Main Results:

  • P2X(7) receptor antagonists and siRNA knockdown significantly inhibited beta-toxin-induced cytotoxicity and cell binding.
  • Beta-toxin and P2X(7) receptor oligomers were found to colocalize in lipid rafts.
  • Preadministration of a P2X(7) antagonist blocked beta-toxin-induced lethality in mice.

Conclusions:

  • The P2X(7) receptor is crucial for beta-toxin-mediated cellular injury.
  • P2X(7) receptor represents a promising therapeutic target for C. perfringens type C infections.

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