Abstract
C. botulinum neurotoxins are acutely toxic materials and act by inhibiting release of the neurotransmitter acetylcholine. The specific nature of this inhibition is discussed and the preparation and purification of Type A toxin specifically for clinical use is described.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Scott AB, Rosenbaum AL, Collins CC : Pharmacological weakening of extra ocular muscles. Invest Ophthalmol 1973, 12: 924–7.
Report of Working Party on Leukaemia in Childhood: Improvement in treatment for children with acute lymphoblastic leukaemia. Lancet 1986, 1: 408.
Syuto B and Kubo S : Purification and chrystallisation of Clostridium botulinum type C toxin. Jpn J Vet Res 1972. 20: 19–30.
Kitamura M, Sakaguchi S, Sakaguchi G : Purification and some properties of Clostridium botulinum type E toxin. Biochem Biophys Acta 1968, 168: 207–17.
Kitamura M, Sakaguchi S, Sakaguchi G : Significance of 12S toxin of Clostridium botulinum type E. J Bacteriol 1968, 98: 1173–8.
Ohishi I and Sakaguchi G : Purification of Clostridium botulinum type F progenitor toxin., Appl Microbiol 1974, 28: 923–8.
Miyazaki S, Iwasaki M, Sakaguchi G : Clostridium botulinum type D toxin: purification, molecular structure, and some immunological properties. Infect Immun 1977, 17: 395–401.
Sugii S and Sakaguchi G : Molecular construction of Clostridium botulinum type A toxins. Infect Immun 1975, 12: 1262–70.
Kazaki S, Sakaguchi S, Sakaguchi G : Purfication and some properties of progenitor toxins of Clostridium botulinum type B. Infect Immun 1974, 10: 750–6.
Shone CC, Hambletpn P, Melling J : Inactivation of Clostridium botulinum type A neurotoxin by trypsin and purification of two tryptic fragments. Proteolytic action near the COOH-terminus of the heavy subunit destroys toxin binding activity. Eur J Biochem 1985, 151: 75–82.
Tse CK, Dolly JO, Hambleton P, Wray D, Melling J Preparation and characterisation of homogenous neurotoxin type A Clostridium botulinum. Its inhibitory action on neural release of acetylcholine in the absence and presence of bun- garotoxin. Eur J Biochem 1982, 122: 493–500.
Beers WH and Reich E : Isolation and characterisation of Clostridium botulinum type B toxin. J Biol Chem 1969, 244: 4473–9.
DasGupta BR and Sugiyama H : Comparative sizes of botulinum type A and B neurotoxins. Toxicon 1977, 15: 357–63.
Evans GM, Williams RS, Shone CC, Hambleton P, Melling J, Dolly JO : Botulinum type B. Its purification, radioidination and interaction with rat-brain synaptosomal membranes. Eur J Biochem 1986, 154: 409–16.
Syuto B and Kubo S : Isolation and molecular size of Clostridium botulinum type C toxin. Appl Environ Microbiol 1977, 33: 400–5.
Syuto B and Kubo S : Separation and characterisation of heavy and light chains from Clostridium botulinum type C toxin and their reconstitution. J Biol Chem 1981, 256: 3712–17.
Terajima J, Syuto B, Ochanda JO, Kubo S : Purification and characterisation of neurotoxin produced by Clostridium botulinum Type C 6813. Infect Immun 1985, 48: 312–17.
Murayama S, Syoto B, Oguma K, Iida H, Kubo S : Comparison of Clostridium botulinum toxin types D and C1 in molecular property, antigenicity and binding ability to rat-brain synapto- somes. Eur J Biochem 1984, 142: 487–92.
Yang KH and Sugiyama H : Purificaiton and properties of Clostridium botulinum type F toxin. Appl Microbiol 1975, 29: 598–603.
DasGupta BR and Sathyamoorthy V : Purification and amino acid composition of type A botulinum neurotoxin. Toxicon 1984, 22: 415–24.
DasGupta BR and Rasmussen S : Purification and amino acid composition of type E botulinum neurotoxin. Toxicon 1983, 21: 535–45.
DasGupta BR and Rasmussen S : Amino acid composition of Clostridium botulinum type F neurotoxin. Toxicon 1983, 21: 566–9.
Kozaki S, Togashi S, Sakaguchi G : Separation of Clostridium botulinum type A derivative toxin into two fragments. Jap J Med Sci Biol 1981, 34: 61–8.
Kozaki S, Miyazaki S, Sakaguchi G : Development of antitoxin with each of two complementary fragments of Clostridium botulinum type B derivative toxin. Infect Immun 1977, 18: 761–6.
Sathyamoorthy V and DasGupta BR : Separation,purification, partial characterisation and comparison of the heavy and light chains of botulinum neurotoxin types A, B and E. J Biol Chem 1985, 260: 10461–6.
Ohishi I, Sugii S, Sakaguchi G : Oral toxicities of Clostridium botulinum toxins in response to molecular size. Infect Immun 1977, 16: 107–9.
Sugii S, Ohishi I, Sakaguchi G : Correlation between oral toxicity and in vitro stability of Clostridium botulinum type A and B toxins of different molecular sizes. Infect Immun 1977, 16: 910–14.
Sugii S, Ohishi I, Sakaguchi G : Intestinal absorption of botulinum toxins of different molecular sizes in rats. Infect Immun 1977, 17: 491–6.
Sakaguchi G, Kozaki S, Ohishi I : Structure and function of botulinum toxins. In Bacterial Protein Toxins. Ed JE Alouf, EJ Fehrenbach, JH Freer, J Jeljiaszewicz. Academic Press, London, 1984, pp 433–43.
Burgen AS, Dickens VF, Zatman LJ : The action of botulinum toxin on the neuromuscular junction. J Physiol (London) 1949, 109: 10–24.
Simpson LL : Ionic requirements for the neuromuscular blocking action of botulinum toxin: implications with regard to synaptic transmission. Neuropharmacol 1971, 10: 673–84.
Simpson LL : The interaction between divalent cations and botulinum toxin type A in the paralysis of the rat phrenic nerve-hemidiaphragm preparation. Neuropharmacol 1973, 12: 165–76.
Thesleff S : Supersensitivity of skeletal muscle produced by botulinum toxin. J Physiol (Lond) 1960 151: 598–607.
Dolly JO, Black J, Williams RS, Melling J . Acceptors for botulinum neurotoxin reside on motor nerve terminals and mediate its internalisation. Nature 1984, 307: 457–60.
Dolly JO, Williams RS, Black JD, Tse CK, Hambleton P, Melling J : Localisation of sites for 125-1 labelled botulinum neurotoxin at the murine neuromuscular junction and its binding to rat brain synaptosomes. Toxicon 1982, 20: 141–l8.
Hirokawa N and Kitamura M : Binding of Clostridium botulinum neurotoxin to the presynaptic membrane in the central nervous system. J Cell Biol 1979, 81: 43–9.
Williams RS, Tse CK, Dolly JO, Hambleton P, Melling J : Radioiodination of botulinum neurotoxin type A with retention of biological activity and its binding to rat brain synaptosomes. Eur J Biochem 1983, 131: 437–45.
Agui T, Syuto B, Oguma K, Iida H and Kubo S : Binding of Clostridium Botulinum type C neurotoxin to rat brain synaptosomes. J Biochem 1983, 94: 521–7.
Agui T, Syuto B, Oguma K, Iida H, Kubo S : The structural relation between the antigenic determinants to monoclonal antibodies and binding sites to rat brain synaptosomes and GTlb gang- lioside in Clostridium botulinum type C neurotoxin. J Biochem 1985, 97: 213–8.
Kozaki S : Interaction of botulinum type A, B and E derivative toxins, with synaptosomes of rat brain, et al.; Naunyn-Schmeideberg's Arch Pharmacol 1979, 308: 67–70.
Dreyer F, Becker C, Bigalke H, Funk J, Penner R, Rosenberg F, Ziegler M : Action of botulinum A toxin and tetanus toxin on synaptic transmission. J Physiol (Paris) 1984, 79: 252–258.
Kozaki S and Sakaguchi G : Binding to mouse brain synaptosomes of Clostridium botulinum type E derivative toxin before and after tryptic activation. Toxicon 1982, 20: 841–6.
Cullcandy SG, Lundh H, Thesleff S : Effects of botulinum toxin on neuromuscular transmission in the rat. J Physiol (London) 1976, 260: 177–203.
Simpson LL : Pharmacological studies on.the sub-cellular site of action of botulinum toxin type A. J Pharmacol Exp ther 1978, 206: 661–9.
Lundh H, Cullcandy SG, Leander S, Thesleff S : Restoration of neurotransmitter release in the botulinum-poisoned skeletal muscle. Brain Res 1976, 110: 194–8.
Lundh H and Thesleff S : The mode of action of 4-aminopyridine and guanidine on transmitter release from motor nerve terminals. Eur J Pharmacol 1977, 42: 411–12.
Simpson LL : The origin, structure and pharmacological activity of botulinum toxin. Pharmacol Rev 1981, 33: 155–88.
Hambleton P, Capel B, Bailey N, Heron N, Crooks A, Melling J : Production, purification and toxoiding of Clostridium botulinum type A toxin. In Biomedical Aspects of Botulism (Lewis, GE, Ed), Academic Press 1981, 247–60.
Shorr N, Seiff SR, Kopelman J : The use of botulinum toxin in blepharospasm. Am J Ophthalmol 1985, 99: 542–6.
Scott AB and Kraft SP : Botulinum toxin injection in the management of lateral rectus paresis. Ophthalmology 1985, 92: 676–83.
Savino PJ, Sergott RC, Bosley TM, Schatz NJ : Hemifacial spasm treated with botulinum A toxin injection. Arch Ophthalmol. 1985, 103: 1305–6.
Mauriello JA : Blepharospasm, Meige syndrome and hemifacial spasm treated with botulinum toxin. Neurology 1985, 35: 1499–500.
Tsui JKC, Eisen A, Stoessl AJ, Calne S, Calne DB : Double-blind study of botulinum toxin in spasmodic torticollis. Lancet 1986. ii: 245–7.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Melling, J., Hambleton, P. & Shone, C. Clostridium botulinum toxins: nature and preparation for clinical use. Eye 2, 16–23 (1988). https://doi.org/10.1038/eye.1988.5
Issue date:
DOI: https://doi.org/10.1038/eye.1988.5
This article is cited by
-
Novel Cosmetic Uses of Botulinum Toxin in the Head and Neck
Current Otorhinolaryngology Reports (2020)
-
Toxin-induced hormesis may restrain aging
Biogerontology (2019)
-
Effects of botulinum a toxin injection on the extraocular muscle fiber layers: Comparison between subtenon injection and intramuscular injection
Japanese Journal of Ophthalmology (2009)
-
From poison to remedy: the chequered history of botulinum toxin
Journal of Neural Transmission (2008)
-
The role of botulinum toxin in whiplash injuries
Current Pain and Headache Reports (2006)


