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Toxins 2015, 7(12), 5268-5275;

Membrane-Binding Mechanism of Clostridium perfringens Alpha-Toxin

Division of Microbiology and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, 2-5274, Gakkocho-dori, Chuo-ku, Niigata 951-8514, Japan
Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan
Author to whom correspondence should be addressed.
Academic Editor: Michel R. Popoff
Received: 27 October 2015 / Revised: 17 November 2015 / Accepted: 30 November 2015 / Published: 3 December 2015
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Clostridium perfringens alpha-toxin is a key mediator of gas gangrene, which is a life-threatening infection that manifests as fever, pain, edema, myonecrosis, and gas production. Alpha-toxin possesses phospholipase C and sphingomyelinase activities. The toxin is composed of an N-terminal domain (1–250 aa, N-domain), which is the catalytic site, and a C-terminal domain (251–370 aa, C-domain), which is the membrane-binding site. Immunization of mice with the C-domain of alpha-toxin prevents the gas gangrene caused by C. perfringens, whereas immunization with the N-domain has no effect. The central loop domain (55–93 aa), especially H….SW84Y85….G, plays an important role in the interaction with ganglioside GM1a. The toxin binds to lipid rafts in the presence of a GM1a/TrkA complex, and metabolites from phosphatidylcholine to diacylglycerol through the enzymatic activity of alpha-toxin itself. These membrane dynamics leads to the activation of endogenous PLCγ-1 via TrkA. In addition, treatment with alpha-toxin leads to the formation of diacylglycerol at membrane rafts in ganglioside-deficient DonQ cells; this in turn triggers endocytosis and cell death. This article summarizes the current the membrane-binding mechanism of alpha-toxin in detail. View Full-Text
Keywords: Clostridium perfringens; alpha-toxin; C-domain; central loop domain; phospholipid; ganglioside GM1a; TrkA; endocytosis; vaccine Clostridium perfringens; alpha-toxin; C-domain; central loop domain; phospholipid; ganglioside GM1a; TrkA; endocytosis; vaccine

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Oda, M.; Terao, Y.; Sakurai, J.; Nagahama, M. Membrane-Binding Mechanism of Clostridium perfringens Alpha-Toxin. Toxins 2015, 7, 5268-5275.

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