Botulinum B toxin

When an action potential approaches the axon terminal, voltage-gated Ca2+ channels (N-type) open and Ca2+ enters the presynapse. Ca2+ ions bind to proteins that connect the synaptic vesicle with the plasma membrane (acronym SNAP), inducing membrane fusion and consequently exocytosis of the neurotransmitter into the synaptic cleft. Botulinum b toxin contains a specific protease which interferes with synaptobrevin (a vesisle protein which interacts with the SNAP proteins) so that vesicles cannot fuse any longer. The inhibition of acetylcholine release can thus cause paralysis and death. 

Neurobloc (Botulinum B toxin). Elan Pharma Ltd. UK Summary of product characteristics,... 

Foran, R, Shone, C. C. and Dolly, J. O., 1994, Differences in the protease activities of tetanus and botulinum B toxins revealed by the cleavage of vesicle-associated membrane protein and various sized fragments. Biochemistry 33 15365-15374. 

C. botulinum C3-toxin and related toxins Rho proteins ADP-ribosylation Inhibition of RhoA, B,C Destruction of the cytoskeleton... 

Park, M.K, Jung, H.H. and Yang, K.H., Binding of Clostridium botulinum type B toxin to rat brain S5maptosome, FEMS Microbiol. Lett., 60, 243-247, 1990. 

Stiles, B.G., Blocker, D., Hale, M.L., Guettholf, M.A. and Barth, H., Clostridium botulinum C2 toxin binding studies with fluorescence-activated cytometry, Toxicon, 40, 1135-1140, 2002. 

Surprisingly perhaps, given its extreme toxicity, botulinum toxin was introduced into medical practice in 1983 to treat patients with squint. Since then, its use has been expanded to include other disorders of muscle control suffered by patients with cerebral palsy or after a severe stroke where the brain cannot control the muscles, which may remain permanently contracted. Tiny amounts of the toxin are injected into the affected muscle, which then becomes paralyzed and, so, relaxed. There are several forms of the toxin that are now marketed as "Botox 7 (type A toxin) and Myobloc (type B toxin). More recently, Botox has been used in "cosmetic77 medicine as a way of reducing lines and wrinkles in the face due to aging. 

Eleopra R, Tugnoli V, Quatrale R, Rossetto O, Montecucco C et al. (2006) Clinical use of non-A botulinum toxins botulinum toxin type C and botulinum toxin type F. Neurotox Res 9 127-31 Evans ER, Sutton JM, Gravett A, Shone CC (2005) Analysis of the substrate recognition domain determinants of botulinum type B toxin using phage display. Toxicon 46 446-53... 

Ohishi, I. (1984). Oral toxicities of Clostridium botulinum type A and B toxins from different strains. Infect. Immun. 43 487-90. 

Aktories K, Ankenbauer T, Sobering B et al. (1986a) ADP-ribosylation of platelet actin by botulinum C2 toxin. In Eur. J. Biochem. 161 155-62... 

Mauss S, Koch G, Kreye VA, et al. (1989) Inhibition of the contraction of the isolated longitudinal muscle of the guinea-pig ileum by botulinum C2 toxin evidence for a role of G/F-actin transition in smooth muscle contraction. In Noun-Schmiedebergs Archiv Pharmacol. 340 345-51 Melamed I, Downey GP, Aktories K, et al. (1991) Microfilament assembly is required for antigen-receptor-mediated activation of human B lymphocytes. In J Immunol. 147 1139-46... 

Prepens U, Just I, Von Eichel-Streiber C et al. (1996) Inhibition of FcsRI-mediated activation of rat basophilic leukemia cells by Clostridium difficile toxin B (mono-glucosyltransferase). In J. Biol. Chem. 271 7324-9 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... 

It is therefore necessary to distinguish between cellular effects caused merely by depolymerization of the actin filaments and effects caused by inactivation of the Rho GTPases which are independent of the actin system. To this end, it is very helpful to compare effects of toxin B with those of Clostridium botulinum C2 toxin. C2 toxin directly acts... 

SollnerTH, Bennett MK, Whiteheart SW, Scheller RH, Rothman JE (1993 b) A protein assembly-disassembly pathway in vitro that may correspond to sequential steps of synaptic vesicle docking, activation, and fusion. In Cell 75 409-18 Stecher B, Weller U, Habermann E, Gratzl M, Anhert-Hilger G (1989) The light chain but not the heavy chain of botulinum A toxin inhibits exocytosis from per-meabilized adrenal chromaffin cells. In FEBS Lett. 255 391 -4... 

V Stecher B, Weller U, Habermann E et of. (1989) The light chain but not the heavy chain of botulinum A toxin inhibits exocytosis from permeabilized adrenal chromaffin cells. FEBS Lett. 255 391 -394. 

Stecher B, Ahnert-Hilger G, Weller U et at. (1992) Amylase release from streptolysin O-permeabilized pancreatic acinar cells effects of Ca GTPyS, cAMP, tetanus toxin and botulinum A toxin. Biochem. J. 283 899-904. 

A-B Toxins are bacterial toxins composed of two peptide chains one (B) that binds to the invaded cell surface, and the other (A) containing the toxin which is then taken-up into the cell. Some examples of exotoxins secreted by the bacteria into the surrounding medium and highly toxic to certain tissues are pathogens causing botuiism (Clostridium botulinum), tetanus (Clostridium tetani) and diptheria (Corynebacterium diphtheria. An example of an A-B endotoxin is Vibrio cholerae. Botulinum toxin and tetanus toxin have their main toxic actions on neuronal tissues, so are described at NEUROTOXINS. 

Some patients fail to respond to treatment with botulinum toxin type A because antibodies which neutralise the toxin are present in their blood, presumably because they have been previously exposed to a subclinical dose of the toxin. Moreover some patients develop the antibodies after treatment with the toxin and then become unresponsive to further treatment. Fortunately this is a rare occurrence because focal injection involves delivery of an extremely low dose of the toxin compared to body weight. Moreover, patients who express the antibodies can often be successfully treated with type F toxin. In the future type B toxin may also prove to be useful. 

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. 

Dezfulian, M., Hatheway, C.L., Yolken, R.H., and Bartlett, J.G., 1984, Enzyme-linked immunosorbent assay for detection of Clostridium botulinum type A and type B toxins in stool samples from infants with botulism, J. Clin. Microbiol. 20 379-383. 

Franciosa, G., Ferreira, J.L., and Hatheway, C.L., 1994, Detection of type A, B, and E botulism neurotoxin genes in Clostridium botulinum and other Clostridium species by PCR evidence of unexpressed type B toxin genes in type A toxigenic organisms, J. Clin. Microbiol. 32 1911-1917. 

Huhtanen, C.N., Whiting, R.C., Miller, A.J., and Call, J.E., 1992, Qualitative correlation of the mouse neurotoxin and enzyme-linked immunoassay for determining Clostridium botulinum types A and B toxins, J. Food Protect. 12 119-127. 

Kozaki, S., Dufrenne, J., Hagenaars, A.M., and Notermans, S., 1979, Enzyme-linked immunosorbent assay (ELISA) for detection of Clostridium botulinum type B toxin, Jpn. J. Med. Sci. Biol. 32 199-205. 

Botulinum neurotoxins (A-G), tetanus toxin Synaptic peptides a) Synapto-brevin b) Syntaxin c) SNAP25 Zinc dependent endoprotease Cleavage of synaptic peptides Inhibition of transmitter release (tetanus, botulism)... 

Botulinum antitoxin Neutralizatien ef the lethal effects of botulinum toxins A, B and E in mice SOOlUmI- eftypeA 5001U mM ef Type B 50IU ml- ef Type E... 

Representatives of medium-size analytes detected by affinity biosensors based on spectroscopy of guided modes include food-safety related analytes such as staphylococcal enterotoxin B , botulinum toxin, and E. coli... 

---