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== Background ==
== Background ==
Botulinum Toxin (BTX) is produced by three species of obligate anaerobe bacterium, primarily ''Clostridium botulism'', but ''Clostridium baratii'' and ''Clostridium butyricum'' also produce the protein <ref>Hall JD, McCroskey LM, Pincomb BJ, Hatheway CL. Isolation of an organism resembling Clostridium baratii which produces type F botulinal toxin from an infant with botulism. J Clin Microbiol. 1985;21:654-655. 36. </ref> <ref>Aureli P, Fenicia L, Pasolini B, Gianfranceschi M, McCroskey LM, Hatheway CL. Two cases of type E infant botulism caused by neurotoxigenic Clostridium butyricum in Italy. J Infect Dis. 1986;154: 207-211. 37. </ref> <ref>Arnon SS. Botulism as an intestinal toxemia. In: Blaser MJ, Smith PD, Ravdin JI, Greenberg HB, Guerrant RL, eds. Infections of the Gastrointestinal Tract. New York, NY: Raven Press; 1995:257-271.</ref>. ''Clostridium botulism'' is commonly found in soil, marine sediments, and the gut of grazing animals <ref>Ward BQ, Carroll BJ, Garrett ES, GB Reese. Survey of the U.S. Gulf Coast for the presence of Clostridium botulinum. Appl Microbiol. 1967;15:629–636. 26.</ref> <ref> Smith LDS. The occurrence of Clostridium botulinum and Clostridium tetani in the soil of the United States. Health Lab Sci. 1978;15:74–80. 27. </ref> <ref>Sugiyama H. Clostridium botulinum neurotoxin. Microbiol Rev. 1980;44:419–448. 28. Dodds KL. Clostridium botulinum in the environment. In: Hauschild AHW </ref> <ref>Dodds KL, eds. Clostridium botulinum—Ecology and Control in Foods. New York, NY: Marcel Dekker, Inc; 1992: 21–51. 29. </ref> <ref>Popoff MR. Ecology of neurotoxigenic strains of clostridia. In: Montecucco C, ed. Current Topics in Microbiology: Clostridial Neurotoxins. The Molecular Pathogenesis of Tetanus and Botulism. Vol 195. Berlin, Germany: Springer-Verlag; 1995: 1–29. </ref>  . BTX is the protein responsible for causing botulism, a potentially fatal illness. Humans can be exposed to the neurotoxin through inhalation, ingestion, or surface wounds. There are seven forms of the protein, named A through G, that are structurally similar but create different immune responses <ref>  Hatheway cL. Clostridium botulinum and other clostridia that produce botulinum neurotoxins. in: Hauschild aHW, Dodds kL, eds. Clostridium botulinum—Ecology and Control in Foods. new york, ny: marcel Dekker, inc; 1992: 3–10 </ref>. The forms of BTX that most often cause botulism in humans are A, B, and E <ref> arnon SS, Schechter r, inglesby tV, et al. botulinum toxin as a biological weapon: medical and public health management. JAMA. 2001;285:1059–1070.</ref>.  
Botulinum Toxin (BTX) is produced by three species of obligate anaerobe bacterium, primarily ''Clostridium botulism'', but ''Clostridium baratii'' and ''Clostridium butyricum'' also produce the protein <ref>Hall JD, McCroskey LM, Pincomb BJ, Hatheway CL. Isolation of an organism resembling Clostridium baratii which produces type F botulinal toxin from an infant with botulism. J Clin Microbiol. 1985;21:654-655. 36. </ref> <ref>Aureli P, Fenicia L, Pasolini B, Gianfranceschi M, McCroskey LM, Hatheway CL. Two cases of type E infant botulism caused by neurotoxigenic Clostridium butyricum in Italy. J Infect Dis. 1986;154: 207-211. 37. </ref> <ref>Arnon SS. Botulism as an intestinal toxemia. In: Blaser MJ, Smith PD, Ravdin JI, Greenberg HB, Guerrant RL, eds. Infections of the Gastrointestinal Tract. New York, NY: Raven Press; 1995:257-271.</ref>. ''Clostridium botulism'' is commonly found in soil, marine sediments, and the gut of grazing animals <ref>Ward BQ, Carroll BJ, Garrett ES, GB Reese. Survey of the U.S. Gulf Coast for the presence of Clostridium botulinum. Appl Microbiol. 1967;15:629–636. 26.</ref> <ref> Smith LDS. The occurrence of Clostridium botulinum and Clostridium tetani in the soil of the United States. Health Lab Sci. 1978;15:74–80. 27. </ref> <ref>Sugiyama H. Clostridium botulinum neurotoxin. Microbiol Rev. 1980;44:419–448. 28. Dodds KL. Clostridium botulinum in the environment. In: Hauschild AHW </ref> <ref>Dodds KL, eds. Clostridium botulinum—Ecology and Control in Foods. New York, NY: Marcel Dekker, Inc; 1992: 21–51. 29. </ref> <ref>Popoff MR. Ecology of neurotoxigenic strains of clostridia. In: Montecucco C, ed. Current Topics in Microbiology: Clostridial Neurotoxins. The Molecular Pathogenesis of Tetanus and Botulism. Vol 195. Berlin, Germany: Springer-Verlag; 1995: 1–29. </ref>  .BTX is only produced by these bacteria when there are anaerobic conditions that induce spore germination. Once produced, the protein can have toxic effects on animals and humans by causing botulism, a potentially fatal illness. BTX is also the active component of Botox.  
 
<Structure load='3BTA' size='350' frame='true' align='right' caption='Botulinum Toxin Neurotoxin Serotype A' scene='Insert optional scene name here' />
<Structure load='3BTA' size='350' frame='true' align='right' caption='Botulinum Toxin Neurotoxin Serotype A' scene='Insert optional scene name here' />


== Structure ==
== Structure ==


BTX is produced as a single chain protein in the bacterium, but becomes active when a protease cuts the protein into a heavy and light chain connected by a single disulfide bong. The heavy chain is approximately 100 kDa and the light chain is 50 kDa (for reviews about structure see references <ref>Sakaguchi G. 1983. Clostridium botulinum toxins. Pharmacol. Ther. 19:165–
There are seven forms of the protein, named A through G, that are structurally similar but create different immune responses <ref>  Hatheway cL. Clostridium botulinum and other clostridia that produce botulinum neurotoxins. in: Hauschild aHW, Dodds kL, eds. Clostridium botulinum—Ecology and Control in Foods. new york, ny: marcel Dekker, inc; 1992: 3–10 </ref>. All seven structures are produced as a single chain protein in the bacterium, but becomes active when a protease cuts the protein into a heavy and light chain connected by a single disulfide bond. The heavy chain is approximately 100 kDa and the light chain is 50 kDa (for reviews about structure see references <ref>Sakaguchi G. 1983. Clostridium botulinum toxins. Pharmacol. Ther. 19:165–
94. </ref> <ref> Minton NP. 1995. Molecular genetics of
94. </ref> <ref> Minton NP. 1995. Molecular genetics of
clostridial neurotoxins. Curr. Top. Microbiol.
clostridial neurotoxins. Curr. Top. Microbiol.
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</ref>.  
</ref>.  
== Disease ==
== Disease ==
Botulism is characterized by paralysis due to the interference of BTX with the release of acetylcholine at nerve synapses. The lethal doses for a human weighing 70 kg is 0.09-0.15 μg when administered intravenously or intramuscularly, 0.70 - 0.90 μg through inhalation, and 70 μg orally <ref>  Franz DR, Pitt LM, Clayton MA, Hanes MA, Rose KJ. Efficacy of prophylactic and therapeutic administration of antitoxin for inhalation botulism. In: DasGupta BR, ed. Botulinum and Tetanus Neurotoxins: Neurotransmission and Biomedical Aspects. New York, NY: Plenum Press; 1993:473-476. </ref> <ref>  Herrero BA, Ecklung AE, Streett CS, Ford DF, King JK. Experimental botulism in monkeys: a clinical pathological study. Exp Mol Pathol. 1967;6:84-95.</ref>.  
 
Of the seven serotypes of BTX, the forms that most often cause botulism in humans are A, B, and E <ref> arnon SS, Schechter r, inglesby tV, et al. botulinum toxin as a biological weapon: medical and public health management. JAMA. 2001;285:1059–1070.</ref>. Humans can be exposed to the neurotoxin through inhalation, ingestion, or surface wounds. Within 12 to 72 hours of exposure to BTX, the inhibition of acetylcholine signaling at nerve synapses creates symptoms of vomiting, nausea, diarrhea, blurred vision, ptosis, dysarthria and dysphagia, and finally weakness of muscles beginning with the head and moving down to the lower extremities <ref> Dembek, Z. F.; Smith, L. A.; Rusnak, J. Botulinum Toxin. In Medical Aspects of Biological Warfare; 2007.</ref>. If not treated, BTX can cause death due to respiratory failure or due to complications when on prolonged medical ventilation.  
 
The lethal doses for a human weighing 70 kg is 0.09-0.15 μg when administered intravenously or intramuscularly, 0.70 - 0.90 μg through inhalation, and 70 μg orally <ref>  Franz DR, Pitt LM, Clayton MA, Hanes MA, Rose KJ. Efficacy of prophylactic and therapeutic administration of antitoxin for inhalation botulism. In: DasGupta BR, ed. Botulinum and Tetanus Neurotoxins: Neurotransmission and Biomedical Aspects. New York, NY: Plenum Press; 1993:473-476. </ref> <ref>  Herrero BA, Ecklung AE, Streett CS, Ford DF, King JK. Experimental botulism in monkeys: a clinical pathological study. Exp Mol Pathol. 1967;6:84-95.</ref>.  
 
The treatment for human exposure to BTX is an antibotulinum serum