Clostridium Binary toxin

The binary Clostridium botulinum toxin C2 blocks the function of actin filaments similarly to cytochalasin D (92). Treatment is for one to four hours in concentrations of 50ng/100ng or 100ng/200ng prior to adding liposomes. 

Clostridium difficile is a commensal Gram-positive anaerobic bacterium of the human intestine, found in about 2-5% of the population. C. difficile is the most serious cause of antibiotic-associated diarrhoea and can lead to pseudomembranous colitis, a severe infection of the colon, often resulting from eradication of the normal gut flora by antibiotics. Discontinuation of causative antibiotic treatment is often curative. In more serious cases, oral administration of metronidazole or vancomycin is the treatment of choice. The bacterium produces several known toxins, including enterotoxin (toxin A) and cytotoxin (toxin B), both of which are responsible for the diarrhoea and inflammation seen in infected patients another toxin, binary toxin, has also been described. 

Pollard TD, Almo S, Quirk S etal. (1994) Structure of actin binding proteins Insights about function at atomic resolution. In Annu. Rev. Cell Biol. 10 207-49 Popoff MR, Rubin EJ, Gill DM et al. (1988) Actin-specific ADP-ribosyltransferase produced by a Clostridium difficile strain. In Infect. Immun. 56 2299-306 Popoff MR, Boquet P (1988) Clostridium spiroforme toxin is a binary toxin which ADP-ribosylates cellular actin. In Biochem. Biophys. Res. Commun. 152 1361—8 Reuner KH, Presek P, Boschek CB et al. (1987) Botulinum C2 toxin ADP-ribosylates actin and disorganizes the microfilament network in intact cells. In Eur. J. Cell Biol. 43 134-40... 

Simpson LL, Stiles BG, Zapeda HH et al. (1987) Molecular basis for the pathological actions of Clostridium perfringens lota toxin. In Infect. Immun. 55 118-22 Simpson LL (1989) The binary toxin produced by Clostridium botulinum enters cells by receptor-mediated endocytosis to exert its pharmacologic effects. In J. Pharmacol. Exp. Ther. 251 1223-8... 

Simpson LL (1989b) The binary toxin produced by Clostridium botulinum enters cells by receptor-mediated endocytosis to exert its pharmacologic effects. In J Pharmacol Exp Then 251 1223-8... 

Popoff MR, Milward FW, Bancillon B, Boquet P (1989) Purification of the Clostridium spiroforme binary toxin and activity of the toxin on HEp-2 cells. Infect Immun 57 2462-2469. 

Another subfamily of ADP-iibosylating toxins modifies G-actin (at Argl77), thereby inhibiting actin polymerization. Members of this family are, for example, C. botulinum C2 toxin and Clostridium perfringens iota toxin. These toxins are binary in structure. They consist of an enzyme component and a separate binding component, which is structurally related to the binding component of anthrax toxin [3]. 

Clostridium botulinum C2 toxin The prototype of a binary actin-ADP-ribosylating toxin 155... 

Barth, H., Roebling, R., Fritz, M. and Aktories, K., The binary Clostridium botulinum C2 toxin as a protein delivery systems. Identification of the minimal protein region necessary for interaction of toxin, J. Biol. Chem., 277, 5074—5081, 2002. 

So far eight different botulinum toxins (A, B, Cl, C2, D, E, F, G) have been described which are produced by various strains of Clostridium botulinum (1). Whereas seven of the botulinum toxins are neurotoxins and block the release at the cholinergic synapses, botulinum C2 toxin is not neurotoxic and acts on various non-neuronal tissues (1-3). It has been shown that component I of the binary botulinum C2 toxin possesses ADP-ribosyltransferase activity (4) on the eukaryotic substrate non-muscle actin (5). Here we describe another ADP-ribosyltransferase which is produced by certain strains of Clostridium botulinum type C. In order to distinguish the novel ADP-ribosyltransferase from botulinum neurotoxin Cl and botulinum C2 toxin we termed this enzyme C3. 

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