Instruct: Given a question, retrieve relevant passages that can help answer the question.
Query: What is the most lethal toxin?
Botulinum toxin is the most acutely lethal toxin that is known. It is produced by the bacterium clostridium botulinum. It acts inside nerve terminals by decreasing the release of acetylcholine, blocking neuromuscular transmission and thereby causing flaccid muscular paralysis. As a result, the muscle is weakened for about 3 to 4 months.
In all cases, illness is caused by the botulinum toxin produced by the bacterium "C. botulinum" in anaerobic conditions and not by the bacterium itself. The pattern of damage occurs because the toxin affects nerves that fire (depolarize) at a higher frequency first.
Botulism is a rare and potentially fatal illness caused by a toxin produced by the bacterium "Clostridium botulinum". The disease begins with weakness, blurred vision, feeling tired, and trouble speaking. This may then be followed by weakness of the arms, chest muscles, and legs. Vomiting, swelling of the abdomen, and diarrhea may also occur. The disease does not usually affect consciousness or cause a fever.
Botulism can be spread in several ways. The bacterial spores which cause it are common in both soil and water. They produce the botulinum toxin when exposed to low oxygen levels and certain temperatures. Foodborne botulism happens when food containing the toxin is eaten. Infant botulism happens when the bacteria develops in the intestines and releases the toxin. This typically only occurs in children less than six months old, as protective mechanisms develop after that time. Wound botulism is found most often among those who inject street drugs. In this situation, spores enter a wound, and in the absence of oxygen, release the toxin. It is not passed directly between people. The diagnosis is confirmed by finding the toxin or bacteria in the person in question.
Prevention is primarily by proper food preparation. The toxin, though not the organism, is destroyed by heating it to more than for longer than 5 minutes. Honey can contain the organism, and for this reason, honey should not be fed to children under 12 months. Treatment is with an antitoxin. In those who lose their ability to breathe on their own, mechanical ventilation may be necessary for months. Antibiotics may be used for wound botulism. Death occurs in 5 to 10% of people. Botulism also affects many other animals. The word is from Latin, "botulus", meaning sausage. Early descriptions of botulism date from at least as far back as 1793 in Germany.
The boomslang's venom is the most potent of all rear-fanged snakes in the world based on LD50. Although its venom may be more potent than some vipers and elapids, it causes fewer fatalities owing to various factors (for example, the fangs' effectiveness is not high compared with many other snakes: the venom dose delivered is low, and boomslangs are generally less aggressive in comparison to other venomous snakes such as cobras and mambas).
In 1820, Justinus Kerner, a small-town German medical officer and romantic poet, gave the first complete description of clinical botulism based on extensive clinical observations of so-called “sausage poisoning”. Following experiments on animals and on himself, he concluded that the toxin acts by interrupting signal transmission in the somatic and autonomic motor systems, without affecting sensory signals or mental functions. He observed that the toxin develops under anaerobic conditions, and can be lethal in minute doses. His prescience in suggesting that the toxin might be used therapeutically earned him recognition as the pioneer of modern botulinum toxin therapy.
Verrucarin A belongs in the class of trichothecenes, a group of sesquiterpene toxins produced by several fungi, namely from the "Fusarium" species, that are responsible for infecting food grains. 
Within the skeleton of the basic trichothecane structure, the olefin and epoxide are crucial for toxicity; ester functionalities and hydroxyl groups often contribute to the toxicity, thereby rendering Verrucarin A as one of the most lethal examples. The mechanism of action for this class of toxins mainly inhibits protein biosynthesis by preventing peptidyl transferase activity. Although initially thought to be potentially useful as anticancer therapeutics, numerous examples of trichothecene derivatives were shown to be too toxic for clinical use.
The "Clostridium botulinum" bacteria are the cause of botulism. Vegetative cells of "C. botulinum" may be ingested. Introduction of the bacteria may also occur via endospores in a wound. When the bacteria are in vivo, they induce flaccid paralysis. This happens because "C. botulinum" produces a toxin which blocks the release of acetylcholine. Botulism toxin blocks the exocytosis of presynaptic vesicles containing acetylcholine (ACh). When this occurs, the muscles are unable to contract. Other symptoms associated with infection from this neurotoxin include double vision, blurred vision, drooping eyelids, slurred speech, difficulty swallowing, dry mouth, and muscle weakness. Botulism prevents muscle contraction by blocking the release of acetylcholine, thereby halting postsynaptic activity of the neuromuscular junction. If its effects reach the respiratory muscles, then it can cause respiratory failure, leading to death.
The venom produced by Collett's snake is similar to the Papuan black snake's and mulga snake's venom. The venom is cytotoxic and has haemolytic activity. Neurotoxins may also be found in its venom as well. "P. colletti" produces about 30 milligrams of venom in one strike. Black snake or tiger snake anti-venom can be administered. It is the world's nineteenth most venomous snake.
With the outbreak of World War II, weaponization of botulinum toxin was investigated at Fort Detrick in Maryland. Carl Lamanna and James Duff developed the concentration and crystallization techniques that Edward J. Schantz used to create the first clinical product. When the Army’s Chemical Corps was disbanded, Schantz moved to the Food Research Institute in Wisconsin, where he manufactured toxin for experimental use and generously provided it to the academic community.
Belcher's sea snake ("Hydrophis belcheri"), which many times is mistakenly called the hook-nosed sea snake ("Enhydrina schistosa"), has been erroneously popularized as the most venomous snake in the world, due to Ernst and Zug's published book "Snakes in Question: The Smithsonian Answer Book" from 1996. Bryan Grieg Fry, a prominent venom expert, has clarified the error: "The hook-nosed myth was due to a fundamental error in a book called "Snakes in Question". In there, all the toxicity testing results were lumped in together, regardless of the mode of testing (e.g. subcutaneous vs. intramuscular vs intravenous vs intraperitoneal). As the mode can influence the relative number, venoms can only be compared within a mode. Otherwise, it's apples and rocks." Belcher's sea snake's actual LD (recorded only intramuscularly) is 0.24 mg/kg and 0.155 mg/kg, less lethal than other sea snakes such as the olive sea snake ("Aipysurus laevis") 0.09 mg/kg and the most toxic intramuscularly, recorded of the sea snakes – the black-banded robust sea snake ("Hydrophis melanosoma") 0.082 mg/kg. The black-banded robust sea snake has also been tested subcutaneously registering at 0.111 mg/kg. more than four times less toxic than the inland taipan's venom. In the LD subcutaneous test, it is actually Dubois' sea snake ("Aipysurus duboisii") which has the most toxic venom of any of the sea snakes tested, registering at 0.044 mg/kg. This is still nearly half as lethal as the inland taipan's venom.
Organophosphate pesticides are one of the top causes of poisoning worldwide, with an annual incidence of poisonings among agricultural workers varying from 3-10% per country.
Belcher's sea snake ("Hydrophis belcheri"), which many times is mistakenly called the hook-nosed sea snake ("Enhydrina schistosa"), has been erroneously popularized as the most venomous snake in the world, due to the first edition of Ernst and book, "Snakes in Question: The Smithsonian Answer Book", published in 1996.
Prominent venom expert Associate Professor Bryan Grieg Fry has clarified the error: "The hook nosed myth was due to a fundamental error in a book called "Snakes in Question". In there, all the toxicity testing results were lumped in together, regardless of the mode of testing (e.g., subcutaneous vs. intramuscular vs. intravenous vs. intraperitoneal). As the mode can influence the relative number, venoms can only be compared within a mode. Otherwise, it's apples and rocks." Belcher's sea snake's actual LD (recorded only intramuscularly) is 0.24 mg/kg and 0.155 mg/kg. Studies on mice and human cardiac cell culture show that venom of the inland taipan, drop by drop, is the most toxic among all snakes.
Toxorhynchites, also called elephant mosquito or mosquito eater, is a genus of diurnal and often relatively colorful mosquitoes, found worldwide between about 35° north and 35° south. It includes the largest known species of mosquito, at up to in length and in wingspan. It is among the many kinds of mosquito that do not consume blood. The adults subsist on carbohydrate-rich materials, such as honeydew, or saps and juices from damaged plants, refuse, fruit, and nectar.
Toxin-antitoxin systems are typically classified according to how the antitoxin neutralises the toxin. In a type I toxin-antitoxin system, the translation of messenger RNA (mRNA) that encodes the toxin is inhibited by the binding of a small non-coding RNA antitoxin that binds the toxin mRNA. The toxic protein in a type II system is inhibited post-translationally by the binding of an antitoxin protein. Type III toxin-antitoxin systems consist of a small RNA that binds directly to the toxin protein and inhibits its activity. There are also types IV-VI, which are less common. Toxin-antitoxin genes are often inherited through horizontal gene transfer and are associated with pathogenic bacteria, having been found on plasmids conferring antibiotic resistance and virulence.
Food-borne botulism results, indirectly, from ingestion of food contaminated with Clostridium spores, where exposure to an anaerobic environment allows the spores to germinate, after which the bacteria can multiply and produce toxin. Critically, "it is ingestion of toxin rather than spores or vegetative bacteria" that causes botulism. Botulism is nevertheless known to be transmitted through canned foods not cooked correctly before canning or after can opening, and so is preventable. Infant botulism cases arise chiefly as a result of environmental exposure and are therefore more difficult to prevent. Infant botulism arising from consumption of honey can be prevented by eliminating honey from diets of children less than 12 months old.
It has been estimated that 7,000–8,000 people per year receive venomous snake bites in the United States, and about five of those people die. Most fatal bites are attributed to the eastern diamondback rattlesnake and the western diamondback rattlesnake. The copperhead accounts for more cases of venomous snake bite than any other North American species; however, its venom is the least toxic, so its bite is seldom fatal.
"mazEF", a toxin-antitoxin locus found in "E. coli" and other bacteria, was proposed to induce programmed cell death in response to starvation, specifically a lack of amino acids. This would release the cell's contents for absorption by neighbouring cells, potentially preventing the death of close relatives, and thereby increasing the inclusive fitness of the cell that perished. This would be an example of altruism and how bacterial colonies could resemble multicellular organisms. However, the ""mazEF"-mediated PCD" has largely been refuted by several studies.
Another theory states that chromosomal toxin-antitoxin systems are designed to be bacteriostatic rather than bactericidal. RelE, for example, is a global inhibitor of translation, is induced during nutrient stress. By shutting down translation under stress, it could reduce the chance of starvation by lowering the cell's nutrient requirements. However, it was shown that several toxin-antitoxin systems, including "relBE", do not give any competitive advantage under any stress condition.
"O. tsutsugamushi" causes a complex and dangerous infection scrub typhus. Infection starts when chiggers bite on the skin during their feeding. The bacteria are deposited at the site of feeding (inoculation), where they multiply. They cause progressive tissue damage (necrosis). Necrosis progresses to inflammation of the blood vessels called vasculitis. This in turn causes inflammation of the lymph nodes, called lymphadenopathy. Within a few days, vasculitis extends to various organs including liver, brain, kidney, meninges and the lung. The disease is responsible for nearly a quarter of all the febrile (high fever) illness in endemic areas. Mortality in severe case or due to improper treatment or misdiagnosis may be as high as 30-70%. About 6% of infected people die untreated, and 1.4% of the patients die even with medical treatment. Moreover, death rate can be as high as 13% where medical treatment is not properly handled. In cases of misdiagnosis and failure of treatment, systemic complications rapidly develop including acute respiratory distress syndrome, acute kidney failure, encephalitis, gastrointestinal bleeding, hepatitis, meningitis, myocarditis, pancreatitis, pneumonia, septic shock, sub-acute thyroiditis, and multi-organ dysfunctions. Harmful symptoms involving multiple organ failure and neurological impairment are difficult to treat, and can be lifelong debilitation or directly fatal. The central nervous system is often affected and result in various complications including cerebellitis, cranial nerve palsies, meningoencephalitis, plexopathy, transverse myelitis, neuroleptic malignant syndrome, and Guillan-Barré syndrome. Death rates due to complications can be up to 14% in brain infections, and 24% with multiple organ failure. It is the major cause of acute encephalitis syndrome in India, where viral infection Japanese encephalitis has been regarded as the main factor.
In any part of the world that uses organophosphates, "C. megacephala" could prove to be beneficial. Organophosphate compounds are used in agriculture and are highly toxic. Organophosphate poisoning often causes death, and in many cases, by evaluating the body tissue and fluids, the toxin can be identified as the source of the poisoning. However, it is somewhat difficult to evaluate the body tissue in a body that is exceedingly decomposed. Nevertheless, a medical examiner in Hawaii worked on a case in which poisoning by malathion, an organophosphate insecticide, was thought to be the cause of death. The victim’s stomach contents and body fat were examined and found to have contained malathion. The fly larvae of "Chrysomya megacephala" and "Chrysomya rufifacies" were also present at the scene on the body and were tested for malathion. Both of these species did contain malathion, but there had been no previous record of organophosphates in their larvae. Studying larvae from decomposed remains may provide an effective method of determining the presence of these toxins in a body that is extremely decayed.
An antitoxin is an antibody with the ability to neutralize a specific toxin. Antitoxins are produced by certain animals, plants, and bacteria. Although they are most effective in neutralizing toxins, they can kill bacteria and other microorganisms. Antitoxins are made within organisms, but can be injected into other organisms, including humans. This procedure involves injecting an animal with a safe amount of a particular toxin. Then, the animal’s body makes the antitoxin needed to neutralize the toxin. Later, the blood is withdrawn from the animal. When the antitoxin is obtained from the blood, it is purified and injected into a human or other animal, inducing passive immunity. To prevent serum sickness, it is often best to use antitoxin generated from the same species (e.g. use human antitoxin to treat humans).
The Lethal Toxin Neutralizing Factor, or LTNF, is a protein found in the blood serum of opossum. The North American Opossum ("Didelphis virginiana") is notable for its ability to survive snake bites. The protein could potentially be used to treat most snake bites as it is capable of neutralizing the venom of major snake families. Furthermore, most modern antivenoms come from horse proteins to which many people are allergic. The molecular weight of LTNF is about 63 kDa.
Anthrax lethal factor endopeptidase (, "lethal toxin") is an enzyme that catalyzes the hydrolysis of mitogen-activated protein kinase kinases. This enzyme is a component of the lethal factor produced by the bacterium "Bacillus anthracis". The preferred cleavage site can be denoted by BBBBxHxH, in which B denotes a basic amino acid Arg or Lys, H denotes a hydrophobic amino acid, and x is any amino acid.
The venom of this species varies very little among Japan, China, and Korea in terms of both its potency and its effects. According to Yoshimitsu (2005), this species and the Okinawan habu, another pitviper, are the most venomous snakes in Japan. The venom's lethality as measured by LD in mice following intraperitoneal injection is in the range 0.3 mg/kg to 1.22 mg/kg. The venom mostly contains haemolytic toxins, but it also has two neurotoxins—an alpha-toxin that is a post-synaptic inhibitor and a beta-toxin that is a pre-synaptic inhibitor. Because the beta-toxin acts pre-synaptically, its effects cannot be blocked or treated by anticholinesterases. The venom contains an anticoagulant, mamushi L-amino-acid oxidase (M-LAO). It also contains the peptide ablomin which is highly similar in amino acid sequence to that of the venom, helothermine, of the beaded lizard ("Heloderma horridum").
"Clostridium perfringens" beta toxin is one of the four major lethal toxins produced by "Clostridium perfringens" Type B and Type C strains. It is a necrotizing agent and it induces hypertension by release of catecholamine. It has been shown to cause necrotic enteritis in mammals and induces necrotizing intestinal lesions in the rabbit ileal loop model. "C. perfringens" beta toxin is susceptible to breakdown by proteolytic enzymes, particularly trypsin. Beta toxin is therefore highly lethal to infant mammals because of trypsin inhibitors present in the colostrum.