The story of Clostridium botulinum: from food poisoning to Botox

Abstract

-In the last fifty years, Clostridium botulinum has become notorious for its ability to produce the deadly botulinum neurotoxins. While botulinum toxin A, better known as Botox™, is universally recognised by the public as a cosmetic enhancement tool, the botulinum neurotoxins are commonly used off-label for many medical conditions in ophthalmology, neurology and dermatology. The versatility of these botulinum toxins has made Clostridium botulinum one of the most widely known bacterial pathogens in medical history. This article outlines the discovery of botulinum toxins through to their present day applications in medicine.KEY WORDS: botulinum toxin, dermatology, food poisoning, human disease, neurology, ophthalmology The botulinum toxinsClostridium botulinum is a rod-shaped, gram-positive anaerobic bacterium. Each of the seven serotypes of this bacterium (A, B, C, D, E, F and G) produce a unique form of botulinum neurotoxin (also designated A to G). 1,2 Types A, B and E are commonly involved in human botulism 3 and found in terrestrial, marine and fresh water environments.Botulinum toxin A, produced by the high yield Hall strain of C botulinum, is the most potent form of botulinum neurotoxin. 4 Botulinum toxin is a high molecular weight protein of 150,000 daltons with noncovalent proteins that protect it from digestive enzymes, thereby making it a highly dangerous food poison. The toxin is destroyed by heating at 80°C for at least one minute.Botulinum toxin A is widely distributed and commercially available as Botox™ (Allergen, Inc) in North America while Dysport™ (Speywood, UK) dominates the European markets. Botulinum toxin B is marketed as Myobloc (Elan Pharmaceuticals) in the USA and Neurobloc (Elan Pharmaceuticals) in Europe; both are currently under review by the US Food and Drug Administration (FDA). 5,6 The FDA specify that Botox™ be distributed in vials of 100±30 mouse units (U) with 1 U equal to the median amount necessary to kill half the sample of mice (LD 50 ). 2,4 Of further note, 1 U of Botox™ is equivalent to 3 ng of botulinum toxin A or 2-5 U Dysport™ (the latter will not be further discussed in this essay). 2 Depending on the medical condition, 30-300 U (1-10 ng) Botox™ injections are required two to six times per year, and administration of the toxin at higher concentrations or too frequently creates the risk of developing antibodies that nullify any beneficial effects. 2 As a pharmaceutical, botulinum toxin A has a large margin of safety with an LD 50 of 3,000 U (100 ng) in humans and side effects from treatment are minimal.All botulinum toxins have a similar mode of action whereby they interfere with the transmission of nerve impulses by inhibiting the release of the acetylcholine neurotransmitter from nerve terminals at the neuromuscular junction. The effect is long lasting but also reversible, as new nerve terminals sprout to replace the formerly inhibited ones. 7,8 Food poisoning from botulinum toxinsIn the late 1700s, botulism, a disease caused by human ingestion of botulinum t...

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