Instruct: Given a question, retrieve documents that can help answer the question.
Query: What is the most lethal toxin?
Botulinum is the most acutely lethal toxin known, with an estimated human median lethal dose (LD50) of 1.3–2.1 ng/kg intravenously or intramuscularly and 10–13ng/kg when inhaled.[2]
In gram-positive bacteria, these are exotoxins or enterotoxins, which may vary depending on the species of bacteria. These are divided into three types. Type I, cell surface-active toxins, disrupt cells without entering, and include superantigens and heat-stable enterotoxins. Type II, membrane-damaging toxins, destroy cell membranes in order to enter and include hemolysins and phospholipases. Type III, intracellular toxins or A/B toxins interfere with internal cell function and include shiga toxin, cholera toxin, and anthrax lethal toxin.
"Clostridium septicum" causes myonecrosis through the release of exotoxins such as the alpha toxin, lethal toxin, and hemolytic toxin 
Venoms of the water cobras, were assayed for lethality, proteolytic activity and protein content. "Naja annulata annulata" and "Naja christyi" venoms averaged 89% protein and lacked proteolytic activity. The murine intraperitoneal LD of "N. a. annulata" and "N. christyi" venoms were 0.143 and 0.120 mg/kg, respectively. Polyvalent antivenom produced by the South African Institute of Medical Research neutralized 575 and 200 LD of "N. a. annulata" and "N. christyi" venoms/ml antivenom, respectively. Cation exchange chromatography resolved four lethal peaks from "N. a. annulata" venom and six lethal peaks from "N. christyi" venom. The major lethal peaks (about 12% of total venom protein) were purified further with molecular sieve chromatography and were characterized as 61 ("N. a. annulata" toxin) and 62 ("N. christyi" toxin) residue polypeptides with four half-cystines. Elucidation of the complete amino acid sequences indicated that these toxins belonged to the short-chain class of postsynaptic neurotoxins. Short-chain neurotoxins 1 from "N. a. annulata" and "N. christyi" had murine intraperitoneal LD of 0.052 and 0.083 mg/kg, respectively, and showed over 80% homology with "N. nigricollis" alpha toxin. Reverse-phase analysis of another peak present in both venoms resolved a toxin that had an N-terminus identical to "N. christyi" short-chain neurotoxin 1. These fractions also contained toxins readily separable from the short-chain isotoxin by preparative reverse-phase chromatography. Amino acid sequencing of the first 28 residues indicated that both toxins were long-chain neurotoxins with identical N-termini. The LD of long-chain neurotoxins 2 from "N. a. annulata" and "N. christyi" venoms were 0.086 and 0.090 mg/kg, respectively. The venoms of these little-known elapids have the lowest intraperitoneal LD of any African "Naja" species studied thus far and have high concentrations of potent postsynaptic neurotoxins.
The lethality of the anthrax disease is due to the bacterium's two principal virulence factors: the poly-D-glutamic acid capsule, which protects the bacterium from phagocytosis by host neutrophils, and the tripartite protein toxin, called anthrax toxin. Anthrax toxin is a mixture of three protein components: protective antigen (PA), edema factor (EF), and lethal factor (LF). PA plus LF produces lethal toxin, and PA plus EF produces edema toxin. These toxins cause death and tissue swelling (edema), respectively.
Anthrax is a disease caused by "Bacillus anthracis", a spore-forming, Gram positive, rod-shaped bacterium (Fig. 1). The lethality of the disease is caused by the bacterium's two principal virulence factors: (i) the polyglutamic acid capsule, which is anti-phagocytic, and (ii) the tripartite protein toxin, called anthrax toxin. Anthrax toxin is a mixture of three protein components: (i) protective antigen (PA), (ii) edema factor (EF), and (iii) lethal factor (LF).
Some binary toxins are composed of an enzymatic component and a component that is involved in membrane interactions and entry of the enzymatic component into the cell. 
The membrane interacting component may have structural domains that are rich in beta sheets. Binary toxins, such as anthrax lethal and edema toxins (Main article: Anthrax toxin), "C. perfringens iota" toxin and "C. difficile" cyto-lethal toxins consist of two components (hence "binary"):In these enzymatic binary toxins, the B component facilitates the entry of the enzymatic 'payload' (A subunit) into the target cell, by forming homooligomeric pores, as shown above for βPFTs. The A component then enters the cytosol and inhibits normal cell functions by one of the following means:
Clostridium difficile toxin B is a toxin produced by the bacteria "Clostridium difficile". "C. difficile " produces two major kinds of toxins that are very potent and lethal; an enterotoxin (Toxin A) and a cytotoxin (Toxin B, this protein).
Diphtheria toxin is extraordinarily potent. The lethal dose for humans is about 0.1 μg of toxin per kg of body weight. Death occurs through necrosis of the heart and liver. Diphtheria toxin has also been associated with the development of myocarditis. Myocarditis secondary to diphtheria toxin is considered one of the biggest risks to unimmunized children.
Evidence of toxin regulation exists across drug types and is present in the case of nicotine. In humans, self-administration of nicotine is moderated such that steady blood concentrations of the toxin are maintained. Moreover, though nicotine is a potent neurotoxin, lethal overdoses are rare and smoking behavior is couched around titration, with number of cigarettes smoked directly tied to changes in nicotine blood concentration. In addition, although typical doses of recreational drugs are often only marginally below the lethal dose, overdose remains rare. For the most part, drug consumption is metered. Thus, proponents of the neurotoxin regulation model of drug use suggest it is highly unlikely that toxin consumption is controlled by the system that motivates and rewards the consumption of macronutrients. Arguing that If drugs and sugar (and other energetically dense foods) stimulate dopamine in the mesolimbic reward system with the same degree of efficiency, then, the drug overdose rates should be comparable in scale to the incidence of obesity.
Dortoxin is a lethal peptide in the venom that is secreted by "Parabuthus transvaalicus". Other toxins in its venom include bestoxin and altitoxin. At least 20% of the peptides in the venom of "P. transvaalicus" consists of these three toxins, and they are thought to be responsible for most of its toxic potency.
The involvement of toxin A and—most importantly—toxin B is the key element that determines the disease caused by "C. difficile". Clinical laboratories have identified these toxins in patients' stool based on antibody and cytotoxicity assays. These bacterial toxins have been shown to be associated with "Clostridium sordellii" hemorrhagic toxin (TcsH), lethal toxin (TcsL), and "Clostridium novyi" alpha toxin (Tcn α), thus, making this cohort to be the large family of toxin clostridial. Because of similarities of these toxins with others, researchers have classified them as the family of large clostridial toxins (LCTs).
A well-known example is the tetrodotoxin of fish species such as "Takifugu rubripes", the famously lethal pufferfish of Japanese fugu. This toxin works by binding to sodium channels in nerve cells, preventing the cells' proper function. A non-lethal dose of this toxin results in temporary paralysis. This toxin is also present in many other species ranging from toads to nemerteans.
The infection of herbivores (and occasionally humans) by the inhalational route normally proceeds as follows: Once the spores are inhaled, they are transported through the air passages into the tiny air sacs (alveoli) in the lungs. The spores are then picked up by scavenger cells (macrophages) in the lungs and are transported through small vessels (lymphatics) to the lymph nodes in the central chest cavity (mediastinum). Damage caused by the anthrax spores and bacilli to the central chest cavity can cause chest pain and difficulty in breathing. Once in the lymph nodes, the spores germinate into active bacilli that multiply and eventually burst the macrophages, releasing many more bacilli into the bloodstream to be transferred to the entire body. Once in the blood stream, these bacilli release three proteins named lethal factor, edema factor, and protective antigen. The three are not toxic by themselves, but their combination is incredibly lethal to humans. Protective antigen combines with these other two factors to form lethal toxin and edema toxin, respectively. These toxins are the primary agents of tissue destruction, bleeding, and death of the host. If antibiotics are administered too late, even if the antibiotics eradicate the bacteria, some hosts still die of toxemia because the toxins produced by the bacilli remain in their system at lethal dose levels.
The median lethal dose, LD (abbreviation for "lethal dose, 50%"), LC (lethal concentration, 50%) or LCt (lethal concentration and time) of a toxin, radiation, or pathogen is the dose required to kill half the members of a tested population after a specified test duration. LD figures are frequently used as a general indicator of a substance's acute toxicity. A lower LD is indicative of increased toxicity.
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.
Some diseases, such as tetanus, cause disease not by bacterial growth but by bacterial production of a toxin. Tetanus toxin is so lethal that humans cannot develop immunity to a natural infection, as the amount of toxin and time required to kill a person is much less than is required by the immune system to recognize the toxin and produce antibodies against it. However the tetanus toxin is easily denatured losing its ability to produce disease, but leaving it able to induce immunity to tetanus when injected into subjects. The denatured toxin is called a toxoid.
Gas gangrene is caused by exotoxin-producing "Clostridium" species (most often "C. perfringens", and "C. novyi",
but less commonly "C. septicum" or "C. ramnosum"), which are mostly found in soil, but also found as normal gut flora, and other anaerobes (e.g., "Bacteroides" and anaerobic streptococci). The exotoxin is commonly found in "C. perfringens" type A strain and is known as alpha toxin. This alpha toxin is a lethal toxin and also known as phospholipase C (lecithinase). It increases vascular permeability and produces necrotizing activity. These environmental bacteria may enter the muscle through a wound and go on to proliferate in necrotic tissue and secrete powerful toxins. These toxins destroy nearby tissue, generating gas at the same time.
The alpha-toxin of "Clostridium botulinum" types C and D, is similar to the "C novyi" beta-toxin.
The A and B toxins of "Clostridium difficile" show homology with the alpha-toxin of "C novyi" as does the lethal toxin of "clostridium sordellii."
The botulinum toxin can cause a severe flaccid paralytic disease in humans and other animals and is the most potent toxin known to mankind, natural or synthetic, with a lethal dose of 1.3–2.1 ng/kg in humans.
In toxicology, the median lethal dose, LD (abbreviation for "lethal dose, 50%"), LC (lethal concentration, 50%) or LCt is a measure of the lethal dose of a toxin, radiation, or pathogen. The value of LD for a substance is the dose required to kill half the members of a tested population after a specified test duration. LD figures are frequently used as a general indicator of a substance's acute toxicity. A lower LD is indicative of increased toxicity.
"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.
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.
Initial studies of mutants revealed that residues on the back side of the central alpha helix were required for super antigenic activity. Changing the histidine at position 135 to alanine caused TSST-1 to be neither lethal or superantigenic. Changes in residues that were in close proximity to H135A, also had the effect of diminishing the lethality and superantigenic quality of these mutants. Although most of these mutants did not result in loss of antigenicity of TSST-1. Tests done using mutagenic TSST-1 toxins indicated that the lethal and superantigenic properties are separable. When Lys-132 in TSST-O was changed to a Glu, the resulting mutant became completely lethal but non superantigenic. The same results, lethal but not superantigenic, were found for TSST-1 Gly16Val. Residues Gly16, Glu132,and Gln 136, located on the back of the back-side groove of the putative TCR binding region of TSST-1, it has been proposed that they are also a part of a second functionally lethal site in the TSST-1.
The A component of anthrax toxin lethal toxin is zinc-metalloprotease, which shows specificity for a conserved family of mitogen-activated protein kinases. The loss of these proteins results in a breakdown of cell signaling, which, in turn, renders the cell insensitive to outside stimuli – therefore no immune response is triggered.