Microbial toxin – Botulinum toxin
Introduction
Microbial toxins are harmful chemicals produced by microorganisms such as bacteria, fungi or algae. As the presence of these microbes is abundant on the Earth, the effects of the toxins can vary between species, with numerous different mechanisms of action. In human history, the dangerous microbial toxin found was able to paralyze a healthy man with just a minuscule amount, and can lead to potentially death. Albeit its lethal reputation, it is quite prevalent, ranging from disease treatment to cosmetic and therapeutic use. This deadly chemical is Botulinum toxins, or more commonly known as Botox, produced by a gram-positive, anaerobic bacterium called Clostridium botulinum.
History
Discovery
One of the earliest records of an outbreak of foodborne botulism (a disease caused by the toxin) took place in 1793 in the village of Wildbad in what is now Baden-Württemberg, Germany. Thirteen people languished, and six passed away after ingesting pork stomach filled with blood sausage, which was a local specialty. This raised a public concern about food poisoning, which led to a warning against consuming this product to avoid “sausage poisoning”. Between 1817 and 1822, German physician Justinus Kerner published the first complete description of the disease, stating that toxins produced in bad sausage under anaerobic conditions is a biological substance that acts on the nervous system and can be lethal even in minute doses. Later on, German physician Dr. Arnold Berlin recognized the toxin in Clostridium botulinum as the cause of botulism.
World War II
Weaponization of botulinum toxin was carried out as a result of the outbreak of World War II. Later on, Carl Lamanna and James Duff came up with the concentration and crystallization techniques that Edward J. Schantz used to create the first clinical product of botulinum toxin. When the Army’s Chemical Corps was dissolved, Schantz moved to the Food Research Institute in Wisconsin, where he manufactured toxins for experimental purposes and supplied them to the academic community.
Cosmetic
The effect of botulinum toxin type-A on reducing and eliminating forehead wrinkles was first discovered by a plastic surgeon from California called Richard Clark. In 1987, he faced a challenge while eliminating the disfigurement caused by only the right side of the forehead muscles functioning, after the other side was paralyzed during a facelift procedure. The patient was longing for a better appearance, but she was undergoing bizarre unilateral right forehead eyebrow elevation while the left eyebrow drooped, and she continuously illustrated deep expressive right forehead wrinkles while the left side was perfectly smooth due to the paralysis. As Clark knew that Botulinum toxin was alright to be used to treat Strabismus (eye muscle disorder) in babies, he requested FDA to let him experiment with Botulinum toxin to paralyze the wrinkling movement of the right forehead muscle and granted their permission. The operation was successful and his discovery was published in the journal Plastic and Reconstructive Surgery in 1989.
Mechanism of actions
Botulinum toxin exerts its effect by cleaving key proteins required for nerve activation. The toxins bind to the receptors on the presynaptic membrane of the neurons that use Acetylcholine as a neurotransmitter. Once they have bound to the nerve terminal, the toxins are taken up into a vesicle by endocytosis and move into the cell. Inside the cell, Botulinum toxins lower the pH, which triggers a reaction that enables the toxins to get into the cytoplasm. The toxins are then cleaved by its protease activity, targeting specific proteins called SNARE (Soluble NSF Attachment Protein Receptor). Through that process, the toxins disrupt the vesicle fusion process, which is vital for the release of acetylcholine into the synaptic gap. Therefore, the release of acetylcholine is hindered, and the motor neurons can’t stimulate muscle fibers, leading to a paralysis. The effects can be temporary or continuous for several months, depending on the body’s ability to regenerate the nerve terminals.
Botulism
Botulism is the disease caused by the poisoning of Botulinum toxins. The most common mode of transmission is by ingesting canned food that has been contaminated with the toxin due to growth of the bacteria in anaerobic condition, even though infection through an open wound is less frequent. In infants, the presence of Clostridium botulinum in their intestines may lead to the release of Botulinum toxin within the lumen, causing a condition called Floppy baby syndrome. The symptoms include abdominal limpness, abnormal suck-swallow pattern of the mouth while ingesting or the inability to maintain proper posture during movement and rest. No matter the case, the toxins inhibit the binding of neurotransmitters to the receptors in neurons, blocking nerves and muscle function and in lethal cases, they can even control the respiratory system and the heart.
Real-life case
In Colorado, 2004, an outbreak of food-borne Botulism occurred. After consuming some improperly stored chili, a family of four experienced a set of abnormal symptoms like vomiting, nausea, blurred vision and muscle weakness. The health conditions of one member exacerbated fast and led to mortality. Another member faced respiratory failure and required extensive medical treatment for recovery.
Prevention
In order to minimize the danger of botulism, many methods of prevention have been carried out. Regarding food-borne botulism, it is recommended to preserve food, especially those canned, in dry and cool places to limit the growth of the bacteria. When making homemade canned food, a pressure canner should be used for low-acid food to destroy the spores of Clostridium botulinum since the temperature of boiling water is not enough to kill them. When it comes to infant botulism, scientists suggest that all the products fed to babies have to be prepared and stored under sanitary conditions to avoid contamination. Moreover, giving money to babies under 12 months old can be really dangerous, for spores of the bacteria may be present there. With wound botulism, safe drug use and proper wound care with sterilized equipment used will lower the risk of infection.
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