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Microbiol Rev. Mar 1992; 56(1): 80–99.
PMCID: PMC372855

Properties and use of botulinum toxin and other microbial neurotoxins in medicine.


Crystalline botulinum toxin type A was licensed in December 1989 by the Food and Drug Administration for treatment of certain spasmodic muscle disorders following 10 or more years of experimental treatment on human volunteers. Botulinum toxin exerts its action on a muscle indirectly by blocking the release of the neurotransmitter acetylcholine at the nerve ending, resulting in reduced muscle activity or paralysis. The injection of only nanogram quantities (1 ng = 30 mouse 50% lethal doses [U]) of the toxin into a spastic muscle is required to bring about the desired muscle control. The type A toxin produced in anaerobic culture and purified in crystalline form has a specific toxicity in mice of 3 x 10(7) U/mg. The crystalline toxin is a high-molecular-weight protein of 900,000 Mr and is composed of two molecules of neurotoxin (ca. 150,000 Mr) noncovalently bound to nontoxic proteins that play an important role in the stability of the toxic unit and its effective toxicity. Because the toxin is administered by injection directly into neuromuscular tissue, the methods of culturing and purification are vital. Its chemical, physical, and biological properties as applied to its use in medicine are described. Dilution and drying of the toxin for dispensing causes some detoxification, and the mouse assay is the only means of evaluation for human treatment. Other microbial neurotoxins may have uses in medicine; these include serotypes of botulinum toxins and tetanus toxin. Certain neurotoxins produced by dinoflagellates, including saxitoxin and tetrodotoxin, cause muscle paralysis through their effect on the action potential at the voltage-gated sodium channel. Saxitoxin used with anaesthetics lengthens the effect of the anaesthetic and may enhance the effectiveness of other medical drugs. Combining toxins with drugs could increase their effectiveness in treatment of human disease.

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  • Ahnert-Hilger G, Dauzenroth ME, Habermann E, Henschen A, Krieglstein K, Mauler F, Weller U. Chains and fragments of tetanus toxin, and their contribution to toxicity. J Physiol (Paris) 1990;84(3):229–236. [PubMed]
  • Argov Z, Mastaglia FL. Drug therapy: Disorders of neuromuscular transmission caused by drugs. N Engl J Med. 1979 Aug 23;301(8):409–413. [PubMed]
  • Ashton AC, Dolly JO. Microtubule-dissociating drugs and A23187 reveal differences in the inhibition of synaptosomal transmitter release by botulinum neurotoxins types A and B. J Neurochem. 1991 Mar;56(3):827–835. [PubMed]
  • Beller M, Middaugh JP. Repeated type E botulism in an Alaskan Eskimo. N Engl J Med. 1990 Mar 22;322(12):855–855. [PubMed]
  • Bergey GK, Habig WH, Bennett JI, Lin CS. Proteolytic cleavage of tetanus toxin increases activity. J Neurochem. 1989 Jul;53(1):155–161. [PubMed]
  • Betley MJ, Somers E, DasGupta BR. Characterization of botulinum type A neurotoxin gene: delineation of the N-terminal encoding region. Biochem Biophys Res Commun. 1989 Aug 15;162(3):1388–1395. [PubMed]
  • Bhattacharyya SD, Sugiyama H. Inactivation of botulinum and tetanus toxins by chelators. Infect Immun. 1989 Oct;57(10):3053–3057. [PMC free article] [PubMed]
  • Bhattacharyya SD, Sugiyama H, Rust P, Lacey D. Evidence that subunits of type A botulinum toxin need not be linked by disulfide. Toxicon. 1988;26(9):817–825. [PubMed]
  • Bigalke H, Dreyer F, Bergey G. Botulinum A neurotoxin inhibits non-cholinergic synaptic transmission in mouse spinal cord neurons in culture. Brain Res. 1985 Dec 23;360(1-2):318–324. [PubMed]
  • Binz T, Kurazono H, Popoff MR, Eklund MW, Sakaguchi G, Kozaki S, Krieglstein K, Henschen A, Gill DM, Niemann H. Nucleotide sequence of the gene encoding Clostridium botulinum neurotoxin type D. Nucleic Acids Res. 1990 Sep 25;18(18):5556–5556. [PMC free article] [PubMed]
  • Binz T, Kurazono H, Wille M, Frevert J, Wernars K, Niemann H. The complete sequence of botulinum neurotoxin type A and comparison with other clostridial neurotoxins. J Biol Chem. 1990 Jun 5;265(16):9153–9158. [PubMed]
  • Bittner MA, DasGupta BR, Holz RW. Isolated light chains of botulinum neurotoxins inhibit exocytosis. Studies in digitonin-permeabilized chromaffin cells. J Biol Chem. 1989 Jun 25;264(18):10354–10360. [PubMed]
  • Bizzini B, Grob P, Glicksman MA, Akert K. Use of the B-IIb tetanus toxin derived fragment as a specific neuropharmacological transport agent. Brain Res. 1980 Jul 7;193(1):221–227. [PubMed]
  • Bizzini B, Stoeckel K, Schwab M. An antigenic polypeptide fragment isolated from tetanus toxin: chemical characterization, binding to gangliosides and retrograde axonal transport in various neuron systems. J Neurochem. 1977 Mar;28(3):529–542. [PubMed]
  • Black JD, Dolly JO. Interaction of 125I-labeled botulinum neurotoxins with nerve terminals. II. Autoradiographic evidence for its uptake into motor nerves by acceptor-mediated endocytosis. J Cell Biol. 1986 Aug;103(2):535–544. [PMC free article] [PubMed]
  • BONVENTRE PF, KEMPE LL. Physiology of toxin production by Clostridium botulinum types A and B. I. Growth, autolysis, and toxin production. J Bacteriol. 1960 Jan;79:18–23. [PMC free article] [PubMed]
  • Borison HL, McCarthy LE, Ellis S. Neurological analysis of respiratory, cardiovascular and neuromuscular effects of brevetoxin in cats. Toxicon. 1985;23(3):517–524. [PubMed]
  • Borodic GE, Cozzolino D, Ferrante R, Wiegner AW, Young RR. Innervation zone of orbicularis oculi muscle and implications for botulinum A toxin therapy. Ophthal Plast Reconstr Surg. 1991;7(1):54–60. [PubMed]
  • Borodic GE, Joseph M, Fay L, Cozzolino D, Ferrante RJ. Botulinum A toxin for the treatment of spasmodic torticollis: dysphagia and regional toxin spread. Head Neck. 1990 Sep-Oct;12(5):392–399. [PubMed]
  • BOROFF DA. Study of toxins of Clostridium botulinum. III. Relation of autolysis to toxin production. J Bacteriol. 1955 Oct;70(4):363–367. [PMC free article] [PubMed]
  • BROOKS VB. The action of botulinum toxin on motor-nerve filaments. J Physiol. 1954 Mar 29;123(3):501–515. [PMC free article] [PubMed]
  • BURGEN ASV, DICKENS F, ZATMAN LJ. The action of botulinum toxin on the neuro-muscular junction. J Physiol. 1949 Aug;109(1-2):10–24. [PMC free article] [PubMed]
  • CAIN HD, FALCO FG. Recurrent tetanus. Calif Med. 1962 Jul;97:31–33. [PMC free article] [PubMed]
  • Catterall WA. Neurotoxins that act on voltage-sensitive sodium channels in excitable membranes. Annu Rev Pharmacol Toxicol. 1980;20:15–43. [PubMed]
  • Cherington M. Botulism. Ten-year experience. Arch Neurol. 1974 Jun;30(6):432–437. [PubMed]
  • Cherington M, Ryan DW. Botulism and guanidine. N Engl J Med. 1968 Apr 25;278(17):931–933. [PubMed]
  • Chiu W, Rankert D, Cumming MA, Robinson JP. Characterization of crystalline filtrate tetanus toxin. J Ultrastruct Res. 1982 Jun;79(3):285–293. [PubMed]
  • Chu FS. Mode of action of mycotoxins and related compounds. Adv Appl Microbiol. 1977;22:83–143. [PubMed]
  • Cornblath DR, Sladky JT, Sumner AJ. Clinical electrophysiology of infantile botulism. Muscle Nerve. 1983 Jul-Aug;6(6):448–452. [PubMed]
  • Cruz Martínez A, Anciones B, Ferrer MT, Díez Tejedor E, Pérez Conde MC, Bescansa E. Electrophysiologic study in benign human botulism type B. Muscle Nerve. 1985 Sep;8(7):580–585. [PubMed]
  • DasGupta BR. Electrophoretic analysis of Clostridium botulinum types A and B hemagglutinins. Can J Microbiol. 1980 Aug;26(8):992–997. [PubMed]
  • DasGupta BR. Structure and biological activity of botulinum neurotoxin. J Physiol (Paris) 1990;84(3):220–228. [PubMed]
  • DasGupta BR, Boroff DA. Separation of toxin and hemagglutinin from crystalline toxin of Clostridium botulinum type A by anion exchange chromatography and determination of their dimensions by gel filtration. J Biol Chem. 1968 Mar 10;243(5):1065–1072. [PubMed]
  • DasGupta BR, Dekleva ML. Botulinum neurotoxin type A: sequence of amino acids at the N-terminus and around the nicking site. Biochimie. 1990 Sep;72(9):661–664. [PubMed]
  • Das Gupta BR, Sugiyama H. Role of a protease in natural activation of Clostridium botulinum neurotoxin. Infect Immun. 1972 Oct;6(4):587–590. [PMC free article] [PubMed]
  • de Paiva A, Dolly JO. Light chain of botulinum neurotoxin is active in mammalian motor nerve terminals when delivered via liposomes. FEBS Lett. 1990 Dec 17;277(1-2):171–174. [PubMed]
  • Do HK, Kogure K, Simidu U. Identification of deep-sea-sediment bacteria which produce tetrodotoxin. Appl Environ Microbiol. 1990 Apr;56(4):1162–1163. [PMC free article] [PubMed]
  • Dreyer F, Schmitt A. Different effects of botulinum A toxin and tetanus toxin on the transmitter releasing process at the mammalian neuromuscular junction. Neurosci Lett. 1981 Nov 4;26(3):307–311. [PubMed]
  • Duchen LW. Changes in motor innervation and cholinesterase localization induced by botulinum toxin in skeletal muscle of the mouse: differences between fast and slow muscles. J Neurol Neurosurg Psychiatry. 1970 Feb;33(1):40–54. [PMC free article] [PubMed]
  • Duchen LW. Motor nerve growth induced by botulinum toxin as a regenerative phenomenon. Proc R Soc Med. 1972 Feb;65(2):196–197. [PMC free article] [PubMed]
  • Duda JJ, Slack JM. Toxin production in Clostridium botulinum as demonstrated by electron microscopy. J Bacteriol. 1969 Feb;97(2):900–904. [PMC free article] [PubMed]
  • DUFF JT, WRIGHT GG, KLERER J, MOORE DE, BIBLER RH. Studies on immunity to toxins of Clostridium botulinum. I. A simplified procedure for isolation of type A toxin. J Bacteriol. 1957 Jan;73(1):42–47. [PMC free article] [PubMed]
  • Eisel U, Jarausch W, Goretzki K, Henschen A, Engels J, Weller U, Hudel M, Habermann E, Niemann H. Tetanus toxin: primary structure, expression in E. coli, and homology with botulinum toxins. EMBO J. 1986 Oct;5(10):2495–2502. [PMC free article] [PubMed]
  • Evans DM, Williams RS, Shone CC, Hambleton P, Melling J, Dolly JO. Botulinum neurotoxin type B. Its purification, radioiodination and interaction with rat-brain synaptosomal membranes. Eur J Biochem. 1986 Jan 15;154(2):409–416. [PubMed]
  • Evans MH. Tetrodotoxin, saxitoxin, and related substances: their applications in neurobiology. Int Rev Neurobiol. 1972;15:83–166. [PubMed]
  • Fairweather NF, Lyness VA. The complete nucleotide sequence of tetanus toxin. Nucleic Acids Res. 1986 Oct 10;14(19):7809–7812. [PMC free article] [PubMed]
  • Fairweather NF, Lyness VA, Pickard DJ, Allen G, Thomson RO. Cloning, nucleotide sequencing, and expression of tetanus toxin fragment C in Escherichia coli. J Bacteriol. 1986 Jan;165(1):21–27. [PMC free article] [PubMed]
  • Feeney RE, Mueller JH, Miller PA. Growth requirements of clostridium tetani: II. Factors exhausted by growth of the organism. J Bacteriol. 1943 Dec;46(6):559–562. [PMC free article] [PubMed]
  • Finn CW, Jr, Silver RP, Habig WH, Hardegree MC, Zon G, Garon CF. The structural gene for tetanus neurotoxin is on a plasmid. Science. 1984 May 25;224(4651):881–884. [PubMed]
  • Frankovich TL, Arnon SS. Clinical trial of botulism immune globulin for infant botulism. West J Med. 1991 Jan;154(1):103–103. [PMC free article] [PubMed]
  • Fujii N, Kimura K, Yashiki T, Indoh T, Murakami T, Tsuzuki K, Yokosawa N, Oguma K. Cloning of a DNA fragment encoding the 5'-terminus of the botulinum type E toxin gene from Clostridium butyricum strain BL6340. J Gen Microbiol. 1991 Mar;137(3):519–525. [PubMed]
  • Fujii N, Kimura K, Murakami T, Indoh T, Yashiki T, Tsuzuki K, Yokosawa N, Oguma K. The nucleotide and deduced amino acid sequences of EcoRI fragment containing the 5'-terminal region of Clostridium botulinum type E toxin gene cloned from Mashike, Iwanai and Otaru strains. Microbiol Immunol. 1990;34(12):1041–1047. [PubMed]
  • Galazka A, Rymkiewicz D, Aleksandrowicz J. Botulinum antitoxins and antibacterial IgM and IgG antibodies in sera of persons immunized with botulinum polytoxoid combined with cholera vaccine. I. Response to botulinum toxoid. Arch Immunol Ther Exp (Warsz) 1976;24(5):631–639. [PubMed]
  • Gill DM. Bacterial toxins: a table of lethal amounts. Microbiol Rev. 1982 Mar;46(1):86–94. [PMC free article] [PubMed]
  • Grecz N, Lin CA, Tang T, So WL, Sehgal LR. The nature of heat resistant toxin in spores of Clostridium botulinum. Jpn J Microbiol. 1967 Dec;11(4):384–394. [PubMed]
  • Green J, Spear H, Brinson RR. Human botulism (type F)--a rare type. Am J Med. 1983 Nov;75(5):893–895. [PubMed]
  • Habermann E, Bernáth S. Preparation, measurement and possible use of human antitoxin against Cl. botulinum A, B, and E toxins. Med Microbiol Immunol. 1975 Jul 2;161(3):203–210. [PubMed]
  • Habermann E, Dreyer F. Clostridial neurotoxins: handling and action at the cellular and molecular level. Curr Top Microbiol Immunol. 1986;129:93–179. [PubMed]
  • Habermann E, Dreyer F, Bigalke H. Tetanus toxin blocks the neuromuscular transmission in vitro like botulinum A toxin. Naunyn Schmiedebergs Arch Pharmacol. 1980 Feb;311(1):33–40. [PubMed]
  • Halpern JL, Habig WH, Neale EA, Stibitz S. Cloning and expression of functional fragment C of tetanus toxin. Infect Immun. 1990 Apr;58(4):1004–1009. [PMC free article] [PubMed]
  • Halpern JL, Smith LA, Seamon KB, Groover KA, Habig WH. Sequence homology between tetanus and botulinum toxins detected by an antipeptide antibody. Infect Immun. 1989 Jan;57(1):18–22. [PMC free article] [PubMed]
  • Hara T, Matsuda M, Yoneda M. Isolation and some properties of nontoxigenic derivatives of a strain of Clostridium tetani. Biken J. 1977 Dec;20(3-4):105–115. [PubMed]
  • Hauser D, Eklund MW, Kurazono H, Binz T, Niemann H, Gill DM, Boquet P, Popoff MR. Nucleotide sequence of Clostridium botulinum C1 neurotoxin. Nucleic Acids Res. 1990 Aug 25;18(16):4924–4924. [PMC free article] [PubMed]
  • Helting TB, Parschat S, Engelhardt H. Structure of tetanus toxin. Demonstration and separation of a specific enzyme converting intracellular tetanus toxin to the extracellular form. J Biol Chem. 1979 Nov 10;254(21):10728–10733. [PubMed]
  • Helting TB, Zwisler O. Structure of tetanus toxin. I. Breakdown of the toxin molecule and discrimination between polypeptide fragments. J Biol Chem. 1977 Jan 10;252(1):187–193. [PubMed]
  • Colquhoun D, Henderson R, Ritchie JM. The binding of labelled tetrodotoxin to non-myelinated nerve fibres. J Physiol. 1972 Dec;227(1):95–126. [PMC free article] [PubMed]
  • Herrero BA, Ecklung AE, Streett CS, Ford DF, King JK. Experimental botulism in monkeys--a clinical pathological study. Exp Mol Pathol. 1967 Feb;6(1):84–95. [PubMed]
  • Hille B. The permeability of the sodium channel to organic cations in myelinated nerve. J Gen Physiol. 1971 Dec;58(6):599–619. [PMC free article] [PubMed]
  • Hoch DH, Romero-Mira M, Ehrlich BE, Finkelstein A, DasGupta BR, Simpson LL. Channels formed by botulinum, tetanus, and diphtheria toxins in planar lipid bilayers: relevance to translocation of proteins across membranes. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1692–1696. [PMC free article] [PubMed]
  • Hughes JM, Blumenthal JR, Merson MH, Lombard GL, Dowell VR, Jr, Gangarosa EJ. Clinical features of types A and B food-borne botulism. Ann Intern Med. 1981 Oct;95(4):442–445. [PubMed]
  • Jackim E, Gentile J. Toxins of a blue-green alga: similarity to saxitoxin. Science. 1968 Nov 22;162(3856):915–916. [PubMed]
  • Jankovic J, Brin MF. Therapeutic uses of botulinum toxin. N Engl J Med. 1991 Apr 25;324(17):1186–1194. [PubMed]
  • Jankovic J, Schwartz K. Botulinum toxin treatment of tremors. Neurology. 1991 Aug;41(8):1185–1188. [PubMed]
  • Jenzer G, Mumenthaler M, Ludin HP, Robert F. Autonomic dysfunction in botulism B: a clinical report. Neurology. 1975 Feb;25(2):150–153. [PubMed]
  • Jones S, Huma Z, Haugh C, Young Y, Starer F, Sinclair L. Central nervous system involvement in infantile botulism. Lancet. 1990 Jan 27;335(8683):228–228. [PubMed]
  • Kao CY, Nishiyama A. Actions of saxitoxin on peripheral neuromuscular systems. J Physiol. 1965 Sep;180(1):50–66. [PMC free article] [PubMed]
  • Kauffman JA, Way JF, Jr, Siegel LS, Sellin LC. Comparison of the action of types A and F botulinum toxin at the rat neuromuscular junction. Toxicol Appl Pharmacol. 1985 Jun 30;79(2):211–217. [PubMed]
  • Kimura K, Fujii N, Tsuzuki K, Murakami T, Indoh T, Yokosawa N, Oguma K. Cloning of the structural gene for Clostridium botulinum type C1 toxin and whole nucleotide sequence of its light chain component. Appl Environ Microbiol. 1991 Apr;57(4):1168–1172. [PMC free article] [PubMed]
  • Kimura K, Fujii N, Tsuzuki K, Murakami T, Indoh T, Yokosawa N, Takeshi K, Syuto B, Oguma K. The complete nucleotide sequence of the gene coding for botulinum type C1 toxin in the C-ST phage genome. Biochem Biophys Res Commun. 1990 Sep 28;171(3):1304–1311. [PubMed]
  • GROSSOWICZ N, KINDLER SH, MAGER J. Toxin production by Clostridium parabotulinum type A. J Gen Microbiol. 1956 Oct;15(2):394–403. [PubMed]
  • Koenig MG, Drutz DJ, Mushlin AI, Schaffner W, Rogers DE. Type B botulism in man. Am J Med. 1967 Feb;42(2):208–219. [PubMed]
  • Kozaki S. Interaction of botulinum type A, B and E derivative toxins with synaptosomes of rat brain. Naunyn Schmiedebergs Arch Pharmacol. 1979 Jul;308(1):67–70. [PubMed]
  • Kozaki S, Sugii S, Oishi I, Sakaguchi S, Sakaguchi G. Proceedings: Clostridium botulinum type A, B, E and F 12S toxins. Jpn J Med Sci Biol. 1975 Feb;28(1):70–72. [PubMed]
  • Laird WJ, Aaronson W, Silver RP, Habig WH, Hardegree MC. Plasmid-associated toxigenicity in Clostridium tetani. J Infect Dis. 1980 Oct;142(4):623–623. [PubMed]
  • Lamanna C, Eklund HW, McElroy OE. Botulinum Toxin (Type A); Including a Study of Shaking with Chloroform as a Step in the Isolation Procedure. J Bacteriol. 1946 Jul;52(1):1–13. [PMC free article] [PubMed]
  • Lamanna C, el-Hage AN, Vick JA. Cardiac effects of botulinal toxin. Arch Int Pharmacodyn Ther. 1988 May-Jun;293:69–83. [PubMed]
  • LAMANNA C, LOWENTHAL JP. The lack of identity between hemagglutinin and the toxin of type A botulinal organism. J Bacteriol. 1951 Jun;61(6):751–752. [PMC free article] [PubMed]
  • Lange DJ, Rubin M, Greene PE, Kang UJ, Moskowitz CB, Brin MF, Lovelace RE, Fahn S. Distant effects of locally injected botulinum toxin: a double-blind study of single fiber EMG changes. Muscle Nerve. 1991 Jul;14(7):672–675. [PubMed]
  • LATHAM WC, BENT DF, LEVINE L. Tetanus toxin production in the absence of protein. Appl Microbiol. 1962 Mar;10:146–152. [PMC free article] [PubMed]
  • Lewis KH, Hill EV. Practical Media and Control Measures for Producing Highly Toxic Cultures of Clostridium botulinum, Type A. J Bacteriol. 1947 Feb;53(2):213–230. [PMC free article] [PubMed]
  • Leyer GJ, Johnson EA. Repression of toxin production by tryptophan in Clostridium botulinum type E. Arch Microbiol. 1990;154(5):443–447. [PubMed]
  • Lomneth R, Martin TF, DasGupta BR. Botulinum neurotoxin light chain inhibits norepinephrine secretion in PC12 cells at an intracellular membranous or cytoskeletal site. J Neurochem. 1991 Oct;57(4):1413–1421. [PubMed]
  • Mahmood NA, Carmichael WW. Paralytic shellfish poisons produced by the freshwater cyanobacterium Aphanizomenon flos-aquae NH-5. Toxicon. 1986;24(2):175–186. [PubMed]
  • Maisey EA, Wadsworth JD, Poulain B, Shone CC, Melling J, Gibbs P, Tauc L, Dolly JO. Involvement of the constituent chains of botulinum neurotoxins A and B in the blockade of neurotransmitter release. Eur J Biochem. 1988 Nov 15;177(3):683–691. [PubMed]
  • Angus PW, Mihaly GW, Morgan DJ, Smallwood RA. Oxygen dependence of omeprazole clearance and sulfone and sulfide metabolite formation in the isolated perfused rat liver. J Pharmacol Exp Ther. 1989 Sep;250(3):1043–1047. [PubMed]
  • Makoff AJ, Oxer MD, Romanos MA, Fairweather NF, Ballantine S. Expression of tetanus toxin fragment C in E. coli: high level expression by removing rare codons. Nucleic Acids Res. 1989 Dec 25;17(24):10191–10202. [PMC free article] [PubMed]
  • Marsden CD, Quinn NP. The dystonias. BMJ. 1990 Jan 20;300(6718):139–144. [PMC free article] [PubMed]
  • Marxen P, Erdmann G, Bigalke H. The translocation of botulinum A neurotoxin by chromaffin cells is promoted in low ionic strength solution and is insensitive to trypsin. Toxicon. 1991;29(2):181–189. [PubMed]
  • Matsuda M, Sugimoto N, Ozutsumi K, Hirai T. Acute botulinum-like intoxication by tetanus neurotoxin in mice. Biochem Biophys Res Commun. 1982 Jan 29;104(2):799–805. [PubMed]
  • Mellanby J. The effect of glutamate on toxin production by Clostridium tetani. J Gen Microbiol. 1968 Nov;54(1):77–82. [PubMed]
  • Mellanby J. Comparative activities of tetanus and botulinum toxins. Neuroscience. 1984 Jan;11(1):29–34. [PubMed]
  • Melling J, Hambleton P, Shone CC. Clostridium botulinum toxins: nature and preparation for clinical use. Eye (Lond) 1988;2(Pt 1):16–23. [PubMed]
  • MEYER KF, EDDIE B. Perspectives concerning botulism. Z Hyg Infektionskr. 1951;133(4):255–263. [PubMed]
  • Miyazaki S, Iwasaki M, Sakaguchi G. Clostridium botulinum type D toxin: purification, molecular structure, and some immunological properties. Infect Immun. 1977 Aug;17(2):395–401. [PMC free article] [PubMed]
  • Mochida S, Poulain B, Eisel U, Binz T, Kurazono H, Niemann H, Tauc L. Exogenous mRNA encoding tetanus or botulinum neurotoxins expressed in Aplysia neurons. Proc Natl Acad Sci U S A. 1990 Oct;87(20):7844–7848. [PMC free article] [PubMed]
  • Molgo J, Comella JX, Angaut-Petit D, Pecot-Dechavassine M, Tabti N, Faille L, Mallart A, Thesleff S. Presynaptic actions of botulinal neurotoxins at vertebrate neuromuscular junctions. J Physiol (Paris) 1990;84(2):152–166. [PubMed]
  • Montecucco C, Papini E, Pitton G. Does tetanus toxin have a sequence homology with the haemagglutinin of influenza virus? Toxicon. 1987;25(9):911–913. [PubMed]
  • Moriishi K, Syuto B, Kubo S, Oguma K. Molecular diversity of neurotoxins from Clostridium botulinum type D strains. Infect Immun. 1989 Sep;57(9):2886–2891. [PMC free article] [PubMed]
  • Mueller JH, Miller PA. Growth Requirements of Clostridium tetani. J Bacteriol. 1942 Jun;43(6):763–772. [PMC free article] [PubMed]
  • MILLER PA, MUELLER JH. Essential role of histidine peptides in tetanus toxin production. J Biol Chem. 1956 Nov;223(1):185–194. [PubMed]
  • Nishida S, Yamagishi T, Tamai K, Sanada I, Takahashi K. Effects of heat selection on toxigenicity, cultural properties, and antigenic structures of clostridia. J Infect Dis. 1969 Nov;120(5):507–516. [PubMed]
  • Nukina M, Miyata T, Sakaguchi S, Sakaguchi G. Detection of neutral sugars in purified type G botulinum progenitor toxin and the effects of some glycolytic enzymes on its molecular dissociation and oral toxicity. FEMS Microbiol Lett. 1991 Apr 15;63(2-3):159–164. [PubMed]
  • Nutt JG, Muenter MD, Aronson A, Kurland LT, Melton LJ., 3rd Epidemiology of focal and generalized dystonia in Rochester, Minnesota. Mov Disord. 1988;3(3):188–194. [PubMed]
  • Oguma K, Iida H, Shiozaki M. Phage conversion to hemagglutinin production in Clostridium botulinum types C and D. Infect Immun. 1976 Sep;14(3):597–602. [PMC free article] [PubMed]
  • Oguma K, Murayama S, Syuto B, Iida H, Kubo S. Analysis of antigenicity of Clostridium botulinum type C1 and D toxins by polyclonal and monoclonal antibodies. Infect Immun. 1984 Feb;43(2):584–588. [PMC free article] [PubMed]
  • Ohishi I. Oral toxicities of Clostridium botulinum type A and B toxins from different strains. Infect Immun. 1984 Feb;43(2):487–490. [PMC free article] [PubMed]
  • Patterson-Curtis SI, Johnson EA. Regulation of neurotoxin and protease formation in Clostridium botulinum Okra B and Hall A by arginine. Appl Environ Microbiol. 1989 Jun;55(6):1544–1548. [PMC free article] [PubMed]
  • Pavlova IB, Sergeeva TI. Ul'trastruktura toksigennykh i netoksigennykh shtammov Cl. tetani. Zh Mikrobiol Epidemiol Immunobiol. 1969 Apr;46(4):12–15. [PubMed]
  • PERKINS WE, TSUJI K. Sporulation of Clostridium botulinum. II. Effect of arginine and its degradation products on sporulation in a synthetic medium. J Bacteriol. 1962 Jul;84:86–94. [PMC free article] [PubMed]
  • Pestronk A, Drachman DB. Motor nerve sprouting and acetylcholine receptors. Science. 1978 Mar 17;199(4334):1223–1225. [PubMed]
  • PILLEMER L, WITTLER RG, et al. The immunochemistry of toxins and toxoids; the crystallization and characterization of tetanol toxin. J Exp Med. 1948 Aug;88(2):205–221. [PMC free article] [PubMed]
  • Popoff M, Boquet P, Gill DM, Eklund MW. DNA sequence of exoenzyme C3, an ADP-ribosyltransferase encoded by Clostridium botulinum C and D phages. Nucleic Acids Res. 1990 Mar 11;18(5):1291–1291. [PMC free article] [PubMed]
  • Poulain B, Mochida S, Wadsworth JD, Weller U, Habermann E, Dolly JO, Tauc L. Inhibition of neurotransmitter release by botulinum neurotoxins and tetanus toxin at Aplysia synapses: role of the constituent chains. J Physiol (Paris) 1990;84(4):247–261. [PubMed]
  • Prescott LM, Altenbern RA. Inducible lysis clostridium tetani. J Bacteriol. 1967 Apr;93(4):1220–1226. [PMC free article] [PubMed]
  • Prescott LM, Altenbern RA. Detection of bacteriophages from two strains of Clostridium tetani. J Virol. 1967 Oct;1(5):1085–1086. [PMC free article] [PubMed]
  • PUTNAM FW, LAMANNA C, SHARP DG. Physiocochemical properties of crystalline Clostridium botulinum type A toxin. J Biol Chem. 1948 Oct;176(1):401–412. [PubMed]
  • RAYNAUD M. Extraction de la toxine tétanique a partir des corps microbiens. Ann Inst Pasteur (Paris) 1951 Apr;80(4):356–377. [PubMed]
  • Ritchie JM, Rogart RB. The binding of labelled saxitoxin to the sodium channels in normal and denervated mammalian muscle, and in amphibian muscle. J Physiol. 1977 Jul;269(2):341–354. [PMC free article] [PubMed]
  • Robinson JP. Purification of tetanus toxin and its major peptides. Methods Enzymol. 1988;165:85–90. [PubMed]
  • Robinson JP, Hash JH. A review of the molecular structure of tetanus toxin. Mol Cell Biochem. 1982 Oct 1;48(1):33–44. [PubMed]
  • Robinson JP, Schmid MF, Morgan DG, Chiu W. Three-dimensional structural analysis of tetanus toxin by electron crystallography. J Mol Biol. 1988 Mar 20;200(2):367–375. [PubMed]
  • Sakaguchi G. Clostridium botulinum toxins. Pharmacol Ther. 1982;19(2):165–194. [PubMed]
  • Sakaguchi G, Sakaguchi S. Oral toxicities of Clostridium botulinum type E toxins of different forms. Jpn J Med Sci Biol. 1974 Aug;27(4):241–244. [PubMed]
  • Sathyamoorthy V, DasGupta BR. Separation, purification, partial characterization and comparison of the heavy and light chains of botulinum neurotoxin types A, B, and E. J Biol Chem. 1985 Sep 5;260(19):10461–10466. [PubMed]
  • SCHANTZ EJ. Biochemical studies on paralytic shellfish poisons. Ann N Y Acad Sci. 1960 Nov 17;90:843–855. [PubMed]
  • Schantz EJ, Ghazarossian VE, Schnoes HK, Strong FM, Springer JP, Pezzanite JO, Clardy J. Letter: The structure of saxitoxin. J Am Chem Soc. 1975 Mar 5;97(5):1238–1238. [PubMed]
  • Schantz EJ, Johnson EA. Dose standardisation of botulinum toxin. Lancet. 1990 Feb 17;335(8686):421–421. [PubMed]
  • SCHANTZ EJ, LAUFFER MA. Diffusion measurements in agar gel. Biochemistry. 1962 Jul;1:658–663. [PubMed]
  • SCHANTZ EJ, STEFANYE D, SPERO L. Observations on the fluorescence and toxicity of botulinum toxin. J Biol Chem. 1960 Dec;235:3489–3491. [PubMed]
  • Schantz EJ, Sugiyama H. Toxic proteins produced by Clostridium botulinum. J Agric Food Chem. 1974 Jan-Feb;22(1):26–30. [PubMed]
  • Schengrund CL, DasGupta BR, Ringler NJ. Binding of botulinum and tetanus neurotoxins to ganglioside GT1b and derivatives thereof. J Neurochem. 1991 Sep;57(3):1024–1032. [PubMed]
  • Scheuer PJ, Takahashi W, Tsutsumi J, Yoshida T. Ciguatoxin: isolation and chemical nature. Science. 1967 Mar 10;155(3767):1267–1268. [PubMed]
  • Scott AB. Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. Ophthalmology. 1980 Oct;87(10):1044–1049. [PubMed]
  • Scott AB. Botulinum toxin injection of eye muscles to correct strabismus. Trans Am Ophthalmol Soc. 1981;79:734–770. [PMC free article] [PubMed]
  • Scott AB. Antitoxin reduces botulinum side effects. Eye (Lond) 1988;2(Pt 1):29–32. [PubMed]
  • Scott AB, Rosenbaum A, Collins CC. Pharmacologic weakening of extraocular muscles. Invest Ophthalmol. 1973 Dec;12(12):924–927. [PubMed]
  • Scott AB, Suzuki D. Systemic toxicity of botulinum toxin by intramuscular injection in the monkey. Mov Disord. 1988;3(4):333–335. [PubMed]
  • Sellin LC, Kauffman JA, Dasgupta BR. Comparison of the effects of botulinum neurotoxin types A and E at the rat neuromuscular junction. Med Biol. 1983 Apr;61(2):120–125. [PubMed]
  • Sellin LC, Thesleff S, Dasgupta BR. Different effects of types A and B botulinum toxin on transmitter release at the rat neuromuscular junction. Acta Physiol Scand. 1983;119(2):127–133. [PubMed]
  • Shone CC, Hambleton 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 Aug 15;151(1):75–82. [PubMed]
  • Siegel LS. Human immune response to botulinum pentavalent (ABCDE) toxoid determined by a neutralization test and by an enzyme-linked immunosorbent assay. J Clin Microbiol. 1988 Nov;26(11):2351–2356. [PMC free article] [PubMed]
  • Siegel LS, Metzger JF. Toxin production by Clostridium botulinum type A under various fermentation conditions. Appl Environ Microbiol. 1979 Oct;38(4):606–611. [PMC free article] [PubMed]
  • Simidu U, Kita-Tsukamoto K, Yasumoto T, Yotsu M. Taxonomy of four marine bacterial strains that produce tetrodotoxin. Int J Syst Bacteriol. 1990 Oct;40(4):331–336. [PubMed]
  • Simpson LL. The origin, structure, and pharmacological activity of botulinum toxin. Pharmacol Rev. 1981 Sep;33(3):155–188. [PubMed]
  • Simpson LL. Fragment C of tetanus toxin antagonizes the neuromuscular blocking properties of native tetanus toxin. J Pharmacol Exp Ther. 1984 Mar;228(3):600–604. [PubMed]
  • Simpson LL. Botulinum toxin and tetanus toxin recognize similar membrane determinants. Brain Res. 1984 Jul 2;305(1):177–180. [PubMed]
  • Somers E, DasGupta BR. Clostridium botulinum types A, B, C1, and E produce proteins with or without hemagglutinating activity: do they share common amino acid sequences and genes? J Protein Chem. 1991 Aug;10(4):415–425. [PubMed]
  • Stefanye D, Schantz EJ, Spero L. Amino acid composition of crystalline botulinum toxin, type A. J Bacteriol. 1967 Jul;94(1):277–278. [PMC free article] [PubMed]
  • Stell R, Thompson PD, Marsden CD. Botulinum toxin in spasmodic torticollis. J Neurol Neurosurg Psychiatry. 1988 Jul;51(7):920–923. [PMC free article] [PubMed]
  • St Louis ME, Peck SH, Bowering D, Morgan GB, Blatherwick J, Banerjee S, Kettyls GD, Black WA, Milling ME, Hauschild AH, et al. Botulism from chopped garlic: delayed recognition of a major outbreak. Ann Intern Med. 1988 Mar;108(3):363–368. [PubMed]
  • 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 Jun;16(3):910–914. [PMC free article] [PubMed]
  • Sugii S, Sakaguchi G. Molecular construction of Clostridium botulinum type A toxins. Infect Immun. 1975 Dec;12(6):1262–1270. [PMC free article] [PubMed]
  • Sugiyama H. Clostridium botulinum neurotoxin. Microbiol Rev. 1980 Sep;44(3):419–448. [PMC free article] [PubMed]
  • Syuto B, Kubo S. Separation and characterization of heavy and light chains from Clostridium botulinum type C toxin and their reconstitution. J Biol Chem. 1981 Apr 25;256(8):3712–3717. [PubMed]
  • Takumi K, Kinouchi T, Kawata T. Isolation of nontoxigenic variants associated with enhanced sporulation and alteration in the cell wall from Clostridium botulinum type a 190L by treatment with detergents. Microbiol Immunol. 1980;24(6):469–477. [PubMed]
  • Taylor CF, Britton P, van Heyningen S. Similarities in the heavy and light chains of tetanus toxin suggested by their amino acid compositions. Biochem J. 1983 Mar 1;209(3):897–899. [PMC free article] [PubMed]
  • Thompson DE, Brehm JK, Oultram JD, Swinfield TJ, Shone CC, Atkinson T, Melling J, Minton NP. The complete amino acid sequence of the Clostridium botulinum type A neurotoxin, deduced by nucleotide sequence analysis of the encoding gene. Eur J Biochem. 1990 Apr 20;189(1):73–81. [PubMed]
  • Truong DD, Hermanowicz N, Rontal M. Botulinum toxin in treatment of tardive dyskinetic syndrome. J Clin Psychopharmacol. 1990 Dec;10(6):438–439. [PubMed]
  • Tse CK, Dolly JO, Hambleton P, Wray D, Melling J. Preparation and characterisation of homogeneous neurotoxin type A from Clostridium botulinum. Its inhibitory action on neuronal release of acetylcholine in the absence and presence of beta-bungarotoxin. Eur J Biochem. 1982 Mar 1;122(3):493–500. [PubMed]
  • Tsuzuki K, Kimura K, Fujii N, Yokosawa N, Indoh T, Murakami T, Oguma K. Cloning and complete nucleotide sequence of the gene for the main component of hemagglutinin produced by Clostridium botulinum type C. Infect Immun. 1990 Oct;58(10):3173–3177. [PMC free article] [PubMed]
  • Tsuzuki K, Yokosawa N, Syuto B, Ohishi I, Fujii N, Kimura K, Oguma K. Establishment of a monoclonal antibody recognizing an antigenic site common to Clostridium botulinum type B, C1, D, and E toxins and tetanus toxin. Infect Immun. 1988 Apr;56(4):898–902. [PMC free article] [PubMed]
  • van Ermengem E. Classics in infectious diseases. A new anaerobic bacillus and its relation to botulism. E. van Ermengem. Originally published as "Ueber einen neuen anaëroben Bacillus und seine Beziehungen zum Botulismus" in Zeitschrift für Hygiene und Infektionskrankheiten 26: 1-56, 1897. Rev Infect Dis. 1979 Jul-Aug;1(4):701–719. [PubMed]
  • Volk WA, Bizzini B, Snyder RM, Bernhard E, Wagner RR. Neutralization of tetanus toxin by distinct monoclonal antibodies binding to multiple epitopes on the toxin molecule. Infect Immun. 1984 Sep;45(3):604–609. [PMC free article] [PubMed]
  • Wadsworth JD, Desai M, Tranter HS, King HJ, Hambleton P, Melling J, Dolly JO, Shone CC. Botulinum type F neurotoxin. Large-scale purification and characterization of its binding to rat cerebrocortical synaptosomes. Biochem J. 1990 May 15;268(1):123–128. [PMC free article] [PubMed]
  • WAGMAN J, BATEMAN JB. Botulinum type A toxin: properties of a toxic dissociation product. Arch Biochem Biophys. 1953 Aug;45(2):375–383. [PubMed]
  • Weller U, Dauzenroth ME, Gansel M, Dreyer F. Cooperative action of the light chain of tetanus toxin and the heavy chain of botulinum toxin type A on the transmitter release of mammalian motor endplates. Neurosci Lett. 1991 Jan 14;122(1):132–134. [PubMed]
  • Weller U, Mauler F, Habermann E. Tetanus toxin: biochemical and pharmacological comparison between its protoxin and some isotoxins obtained by limited proteolysis. Naunyn Schmiedebergs Arch Pharmacol. 1988 Aug;338(2):99–106. [PubMed]
  • 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 brain synaptosomes. Eur J Biochem. 1983 Mar 15;131(2):437–445. [PubMed]
  • Yasumoto T, Nagai H, Yasumura D, Michishita T, Endo A, Yotsu M, Kotaki Y. Interspecies distribution and possible origin of tetrodotoxin. Ann N Y Acad Sci. 1986;479:44–51. [PubMed]
  • Yotsu M, Yamazaki T, Meguro Y, Endo A, Murata M, Naoki H, Yasumoto T. Production of tetrodotoxin and its derivatives by Pseudomonas sp. isolated from the skin of a pufferfish. Toxicon. 1987;25(2):225–228. [PubMed]

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