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

被引：43

作者：

Knapp, Oliver ^{[1
]}

Maier, Elke ^{[2
]}

Ben Mkaddem, Sanae ^{[3
]}

Benz, Roland ^{[2
]}

Bens, Marcelle ^{[3
]}

Chenal, Alexandre ^{[4
]}

Geny, Blandine ^{[1
]}

Vandewalle, Alain ^{[3
]}

Popoff, Michel R. ^{[1
]}

机构：

[1] Inst Pasteur Bacteries Anaerobies & Toxines, F-75724 Paris, France

[2] Univ Wurzburg, Theodor Boveri Inst, Biozentrum, Lehrstuhl Biotechnol, D-97074 Wurzburg, Germany

[3] Univ Paris 07, CRB3, INSERM, U773, F-75870 Paris, France

[4] Inst Pasteur, CNRS, URA2185, Unite Biochim Interact Macromol, F-75724 Paris 15, France

来源：

TOXICON | 2010年 / 55卷 / 01期

关键词：

Alpha-toxin; Clostridium septicum; Clostridium perfringens; Channel formation; Lipid bilayer; Cell necrosis; Transepithelial resistance; PERFRINGENS EPSILON-TOXIN; ADENYLATE-CYCLASE TOXIN; ION-PERMEABLE CHANNELS; GPI-ANCHORED PROTEINS; ESCHERICHIA-COLI; AEROMONAS-HYDROPHILA; NUCLEOTIDE-SEQUENCE; MEMBRANE-CHANNEL; EPITHELIAL-CELLS; LIPID-BILAYERS;

D O I：

10.1016/j.toxicon.2009.06.037

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：61 / 72

页数：12

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