Clostridium Translocation

Blocker, D., Bachmeyer, C., Benz, R., Aktories, K. and Barth, H., Channel formation by the binding component of Clostridium botulinum C2 toxin glutamate 307 of C2II affects channel properties in vitro and pH-dependent C2I translocation in vivo, Biochem., 42, 5368-5377, 2003. 

Harris JB, Grubb BD, Maltin CA, Dixon R (2000) The neurotoxicity of the venom phospholipases A(2), notexin and taipoxin. Exp Neurol 161 517-26 Haug G, Wilde C, Leemhuis J, Meyer DK, Aktories K et al. (2003) Cellular uptake of Clostridium botulinum C2 toxin membrane translocation of a fusion toxin requires unfolding of its dihydrofolate reductase domain. Biochemistry 42 15284-91 Hauschild A (1993) Epidemiology of human foodborne botulism. In Hauschild A, Dodds KL (eds) Clostridium botulinum ecology and control in foods. Marcel Dekker, Inc. New York, pp 69-104... 

Toxin B is an intracellularly acting cytotoxin and enters the cell via a receptor-mediated endocytosis pathway to reach the endosomes, from which the toxin is translocated to the cytoplasm (Florin and The-lestam, 1986 Henriques etal., 1987). Because of this specific mode of entry, the toxin concentration needed for intoxication of cells is low (lOOng/ml for about 4h). In contrast, Clostridium bofulinum exoenzyme C3 (23.5 kDa), which ADP-ribosylates the Rho subtype proteins RhoA, B and C only, enters the cells by a non-specific uptake process, possibly by pinocytosis. Therefore, C3 has to be applied in high concentrations (about 30 g/ml) for 24 h or longer. 

The Clostridium bofulinum exoenzyme C3 is able to ADP-ribosylote the small G-protein, rho, in a cell free system, but is unable to enter cells (except at very high concentrations) because it lacks a B-moiety. Constructs where exoenzyme C3 was linked to the N-terminal end of diphtheria toxin or to toxin where the N-terminal part of the A-fragment had been deleted, were able to translocate the exoenzyme-containing fusion protein into the cytosol and interfere with the organization of actin filaments (Aullo et a/., 1993). 

---