Botulinum toxin Botulinum toxin is a protein produced
Botulinum toxin
Botulinum toxin is a protein produced by the bacterium Clostridium botulinum, and is considered the most powerful neurotoxin ever discovered. Botulinum toxin causes Botulism poisoning, a serious and lifethreatening illness in humans and animals. Popularly known by one of its trade names, Botox or Dysport or Xeomin, it is used for various cosmetic and medical procedures
C. botulinum is an anaerobic, Gram positive, spore-forming rod. Botulin toxin is one of the most powerful known toxins: about one microgram is lethal to humans. It acts by blocking nerve function and leads to respiratory and musculoskeletal paralysis. In all cases illness is caused by the toxin made by C. botulinum, not by the bacterium itself. The pattern of damage occurs because the toxin affects nerves that are firing more often. Specifically, the toxin acts by blocking the production or release of acetylcholine at synapses and neuromuscular junctions. Death occurs due to respiratory failure.
Botulism toxins are produced by these bacteria: Clostridium botulinum, C. butyricum, C. baratii and C. argentinense. Foodborne botulism can be transmitted through food that has not been heated correctly prior to being canned or food that was not cooked correctly from a can. Most infant botulism cases cannot be prevented because the bacteria that cause this disease are in soil and dust. The bacteria can be found inside homes on floors, carpet, and countertops even after cleaning. Honey can contain the bacteria that cause infant botulism, so children less than twelve months old should not be fed honey. Honey is safe for persons one year of age and older.
There are seven serologically distinct toxin types, designated A through G. The toxin is a two-chain polypeptide with a 100 -k. Da heavy chain joined by a disulfide bond to a 50 -k. Da light chain. This light chain is an enzyme (a protease) that attacks one of the fusion proteins (SNAP-25, syntaxin or synaptobrevin) at a neuromuscular junction, preventing vesicles from anchoring to the membrane to release acetylcholine. By inhibiting acetylcholine release, the toxin interferes with nerve impulses and causes flaccid (sagging) paralysis of muscles in botulism, as opposed to the spastic paralysis seen in tetanus.
The heavy chain of the toxin is particularly important for targeting the toxin to specific types of axon terminals. The toxin must get inside the axon terminals in order to cause paralysis. Following the attachment of the toxin heavy chain to proteins on the surface of axon terminals, the toxin can be taken into neurons by endocytosis. The light chain is able to cleave endocytotic vesicles and reach the cytoplasm. The light chain of the toxin has protease activity. The type A toxin proteolytically degrades the SNAP-25 protein. The SNAP-25 protein is required for vesicle fusion that releases neurotransmitters from the axon endings (in particular Acetylcholine).
The toxin enters the body in one of three ways: by colonization of the digestive tract by the bacterium in children (infant botulism) or adults (adult intestinal toxemia), by ingestion of toxin from foods (foodborne botulism) or by contamination of a wound by the bacterium (wound botulism) All forms lead to paralysis that typically starts with the muscles of the face and then spreads towards the limbs. In severe forms, it leads to paralysis of the breathing muscles and causes respiratory failure. In view of this life-threatening complication, all suspected cases of botulism are treated as medical emergencies, and public health officials are usually involved to prevent further cases from the same source
Signs and symptoms: The muscle weakness of botulism characteristically starts in the muscles supplied by the cranial nerves. A group of twelve nerves controls eye movements, the facial muscles and the muscles controlling chewing and swallowing. Double vision, drooping of both eyelids, loss of facial expression and swallowing problems may therefore occur, as well as difficulty with talking. The weakness then spreads to the arms (starting in the shoulders and proceeding to the forearms) and legs (again from the thighs down to the feet). Severe botulism leads to reduced movement of the muscles of respiration, and hence problems with gas exchange. This may be experienced as dyspnea (difficulty breathing), but when severe can lead to respiratory failure, due to the buildup of unexhaled carbon dioxide and its resultant depressant effect on the brain. This may lead to coma and eventually death if untreated.
Treatment: Most infant botulism patients require supportive care in a hospital setting. The only drug currently available to treat infant botulism is Botulism Immune Globulin Intravenous-Human (BIG-IV or Baby. BIG). Baby. BIG was developed by the Infant Botulism Treatment and Prevention Program at the California Department of Public Health. The respiratory failure and paralysis that occur with severe botulism may require a patient to be on a ventilator for weeks, plus intensive medical and nursing care. After several weeks, the paralysis slowly improves. If diagnosed early, foodborne and wound botulism can be treated by inducing passive immunity with a horse-derived antitoxin, which blocks the action of toxin circulating in the blood
Prevention: Although the botulinum toxin is destroyed by thorough cooking over the course of a few minutes, the spore itself is not killed by the temperatures reached with normal sea-level-pressure boiling, leaving it free to grow and again produce the toxin when conditions are right. Commercially canned goods are required to undergo a "botulinum cook" at for 3 minutes.
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