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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 name="Hall"> PMID: 3988908</ref> <ref name="Aureli"> PMID: 3722863</ref> <ref name="Arnon"> PMID: 11209178</ref>. ''Clostridium botulism'' is commonly found in soil, marine sediments, and the gut of grazing animals <ref name="Ward"> PMID: 5340653</ref> <ref name="Smith"> PMID: 355208</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 name="Popoff"> PMID: 8542750</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.  

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 name="Minton"> PMID: 8542753</ref> <ref> Oguma K, Fujinaga Y, Inoue K. 1995.Structure and function of Clostridium botulinum toxins. Microbiol. Immunol. 39:161–68 </ref> <ref name="Lacy"> PMID: 10518945</ref> <ref name="Popoff" />).

The active form of BTX has three functional domains responsible for binding, translocation, and catalysis <ref name="Montecucco"> PMID: 8771234</ref>. The C terminus of the heavy chain is responsible for binding a ganglioside and protein receptors on the nerve terminal while the N terminus half functions by translocating the protein across the membrane by signaling endocytosis <ref name="Dolly"> PMID: 6694738</ref>. Once in a vesicle in the cytosol of a nerve terminal, the light chain dissociates from the heavy chain and cleaves SNARE proteins involved in synaptic vesicle fusion. The cleavage of these SNARE proteins, VAMP, SNAP-25, and syntax, depends on the serotype of BTX where each serotype cuts at a different place. The cut SNAREs inhibit the binding of vesicles containing acetylcholine which effectively stops the signaling from nerves to muscle cells, resulting in paralysis <ref name="Lacy" />

Of the seven serotypes of BTX, the forms that most often cause botulism in humans are A, B, and E <ref name="Arnon" /> 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 name="Herrero"> PMID: 4960839</ref>.

The treatment for human exposure to BTX is an antitoxin developed from horse plasma. Horses are exposed naturally to "Clostridium botulism" in their gut and therefore produce antibodies against "Clostridium botulism" in case the bacteria population grows to an extreme. Antitoxins have been developed by isolating this antibody from horses, and in some cases, removing the Fc from the immunoglobulin and leaving the F(ab')2 fragment. By removing the Fc fragment, the incidence of hypersensitivity and anaphylaxis. There are divalent, trivalent, and heptavalent antitoxins available that treat botulinum serotypes A and B (divalent), serotypes A, B, and C (trivalent), and all seven serotypes (heptavalent). An antitoxin, botulism immune globulin (BabyBIG) has also been developed that can be used in infantile cases of botulism. BabyBIG is produced by using the human antibodies produced when a person is injected with pentavalent botulinum toxoid vaccine. By using human antibodies, there is less of a risk of anaphylactic shock and hypersensitivity to equine antigens <ref> Dembek, Z. F.; Smith, L. A.; Rusnak, J. Botulinum Toxin. In Medical Aspects of Biological Warfare; 2007.</ref>.

The antitoxins cannot stop BTX from inhibiting acetylcholine signaling once it has started in parts of the body, but it can stop the progression of paralysis. Thus, treatment can decrease fatalities to 5-10% if administered within 24 hours of exposure <ref> Dembek, Z. F.; Smith, L. A.; Rusnak, J. Botulinum Toxin. In Medical Aspects of Biological Warfare; 2007.</ref>.

Due to the powerful toxicity of BTX, the protein could be used as a biological weapon. The countries that have developed BTX to be used in warfare include Japan, Germany, United States, Russia, and Iraq <ref> Dembek, Z. F.; Smith, L. A.; Rusnak, J. Botulinum Toxin. In Medical Aspects of Biological Warfare; 2007. </ref>.

BTX has also been used medically and cosmetically as Botox. Various disorders characterized by involuntary muscle contraction can be treated with a small injection of BTX to weaken the spastic muscles for three to four months <ref name="Nayyar"> PMID: 25654058</ref>. Some of these diseases include

cervical dystonia, blepharospasm, strabismus, chronic migraines, primary axillary hyperhidrosis, oesophageal achalasia, vaginismus, and detrusor overactivity among others.  

Botulinum toxin is also used in small quantities to prevent the formation of wrinkles. Small muscles in the face create wrinkles after years of repeated contraction <ref>Botulinum Toxin Injection for Facial Wrinkles - American Family Physician http://www.aafp.org/afp/2014/0801/p168.html#sec-1 (accessed Apr 28, 2016).</ref>. By injecting botulinum toxin into specific muscles, contraction is inhibited and wrinkles are prevented. Continual injections are needed every few weeks because the SNAP-25 proteins regenerate allowing signaling for muscle contraction to begin again.