Botulinum Toxin

Abstract

Botulinum neurotoxin is produced by the bacteria Clostridium botulinum and causes the rare paralytic disease botulism. Purified toxin has gained acceptance to temporarily treat certain human diseases characterized by excessive nerve activity, and also for cosmetic treatment of facial ageing (e.g. BOTOX®).

Keywords: botulism; clostridium botulinum; SNARE protein; zinc metalloprotease; bioterrorism

Figure 1.

Sequence analysis shows the level of similarity and diversity among the seven BoNTs. While these toxins form a class of genetically related proteins, they are quite varied. BoNT C and D are the most closely related serotypes being 71.2% homologous. BoNT E/F and B/G have 63.9% and 56.8% homology, respectively. BoNT A is distantly homologous to BoNT E with only 33% homology. Overall homology between all of the BoNTs is about 45%.

Figure 2.

Route of BoNT poisoning. BoNT A, B and E can escape degradation while in the GI tract (1) and pass through the intestinal lining to enter either blood or lymph capillaries. Toxin that enters the blood capillaries passes through the liver (a) where it proceeds along a circuitous path throughout the cardiovascular system before being distributed systemically. Toxin that enters lymph capillaries is transported directly from the intestines upwards through the mesenteric lymph nodes prior to the intestinal lymphatic trunk (2 and 3) leading to the thoracic duct (4) where toxin enters the subclavian vein immediately prior to entering the right side of the heart. Cardiac tissue is insensitive to BoNT but serves to distribute toxin throughout the body.

Figure 3.

Model of the intoxication pathway adapted from Simpson . BoNT is a 150 kDa protein composed of a binding and channel‐forming heavy chain HC of 100 kDa and a catalytic LC of 50 kDa. After internalization, toxin activity of the LC crosses the endosomal membrane by moving through the HC channel.

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References

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Further Reading

Adler M, Oyler GA, Keller JE and Lebeda FJ (2001) Pharmacological countermeasures for botulinum intoxication. In: Somani SM and Romano JA (eds) Chemical Warfare Agents: Toxicity at Low Levels, Chap. 12. New York: CRC Press.

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How to Cite close
Keller, James E, and Vann, Willie F(Jan 2006) Botulinum Toxin. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0004218]