Clostridium septicum alpha-toxin forms pores and induces rapid cell necrosis

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• 作者：Oliver Knapp ; Elke Maier ; Sanae Ben Mkaddem ; Rol ; Benz ; Marcelle Bens ; Alex ; re Chenal ; Bl ; ine Geny ; Alain V ; ewalle ; Michel R. Popoff
• 关键词：Alpha-toxin ; Clostridium septicum ; Clostridium perfringens ; Channel formation ; Lipid bilayer ; Cell necrosis ; Transepithelial resistance
• 刊名：Toxicon
• 出版年：2010
• 出版时间：January 2010
• 年：2010
• 卷：55
• 期：1
• 页码：61-72
• 全文大小：1077 K

文摘

Alpha-toxin is the unique lethal virulent factor produced by Clostridium septicum, which causes traumatic or non-traumatic gas gangrene and necrotizing enterocolitis in humans. Here, we analyzed channel formation of the recombinant septicum alpha-toxin and characterized its activity on living cells. Recombinant septicum alpha-toxin induces the formation of ion-permeable channels with a single-channel conductance of about 175 pS in 0.1 M KCl in lipid bilayer membranes, which is typical for a large diffusion pore. Septicum alpha-toxin channels remained mostly in the open configuration, displayed no lipid specificity, and exhibited slight anion selectivity. Septicum alpha-toxin caused a rapid decrease in the transepithelial electrical resistance of MDCK cell monolayers grown on filters, and induced a rapid cell necrosis in a variety of cell lines, characterized by cell permeabilization to propidium iodide without DNA fragmentation and activation of caspase-3. Septicum alpha-toxin also induced a rapid K⁺ efflux and ATP depletion. Incubation of the cells in K⁺-enriched medium delayed cell death caused by septicum alpha-toxin or epsilon-toxin, another potent pore-forming toxin, suggesting that the rapid loss of intracellular K⁺ represents an early signal of pore-forming toxins-mediated cell necrosis.