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Bacterial exotoxins are proteins of disease-causing bacteria that are usually secreted and have deleterious effects. Several hundred are known. In some extreme cases a single toxin accounts for the principal symptoms of a disease, such as diphtheria, tetanus, and cholera. Bacteria that cause local infections with pus often produce many toxins that affect the tissues around the infection site or are distributed to remote organs by the blood. See Cholera, Diphtheria, Staphylococcus
Toxins may assist the parent bacteria to combat host defense systems, to increase the supply of certain nutrients such as iron, to invade cells or tissues, or to spread between hosts. Sometimes the damage suffered by the host organism has no obvious benefit to the bacteria. For example, botulinal neurotoxin in spoiled food may kill the person or animal that eats it long after the parent bacteria have died. In such situations it is assumed that the bacteria benefit from the toxin in some other habitat and that the damage to vertebrates is accidental. See Food poisoning
Certain bacterial and plant toxins have the unusual ability to catalyze chemical reactions inside animal cells. Such toxins are always composed of two functionally distinct parts termed A and B, and they are often called A-B toxins. The B part binds to receptor molecules on the animal cell surface and positions the toxin upon the cell membrane. Subsequently, the enzymically active A portion of the toxin crosses the animal cell membrane and catalyzes some intracellular chemical reaction that disrupts the cell physiology or causes cell death. See Immunologic cytotoxicity
A large group of toxins breach the normal barrier to free movement of molecules across cell membranes. In sufficient concentration such cytolytic toxins cause cytolysis, a process by which soluble molecules leak out of cells, but in lower concentration they may cause less obvious damage to the cell's plasma membrane or to its internal membranes. See Cell membranes, Cell permeability
Tetanus and botulinal neurotoxins block the transmission of nerve impulses across synapses. Tetanus toxin blockage results in spastic paralysis, in which opposing muscles contract simultaneously. The botulinal neurotoxins principally paralyze neuromuscular junctions and cause flaccid paralysis.
Gram-negative bacteria, such as Salmonella and Hemophilus, have a toxic component in their cell walls known as endotoxin or lipopolysaccharide. Among other detrimental effects, endotoxins cause white blood cells to produce interleukin-1, a hormone responsible for fever, malaise, headache, muscle aches, and other nonspecific consequences of infection. The exotoxins of toxic shock syndrome and of scarlet fever induce interleukin-1 and also tumor necrosis factor, which has similar effects. See Endotoxin, Scarlet fever, Toxic shock syndrome
Toxoids are toxins that have been exposed to formaldehyde or other chemicals that destroy their toxicities without impairing immunogenicity. When injected into humans, toxoids elicit specific antibodies known as antitoxins that neutralize circulating toxins. Such immunization (vaccination) is very effective for systemic toxinoses, such as diphtheria and tetanus. See Antibody, Immunity, Vaccination
a substance of bacterial, vegetable, or animal origin capable of depressing physiological functions in such a way as to cause sickness or death in animals and humans. Chemically, toxins are either proteins or polypeptides. In contrast to other organic and inorganic poisonous substances, toxins, upon entering an organism, cause the formation of antibodies. (The molecular weight of toxins exceeds 4,000–5,000; substances of lower molecular weight are not immunogenic.) Toxins are contained in the poisons produced by, for example, snakes, scorpions, spiders, and certain plants.
The most widely distributed and thoroughly studied toxins are the bacterial type, of which several hundred are known. Bacterial toxins are subdivided into exotoxins and endotoxins. Exotoxins, which are secreted into the environment as a result of the vital activities of bacteria, are specific in their effect on organisms. Examples include neurotoxins and cytotoxins. Certain microorganisms secrete highly potent toxins that cause botulism, tetanus, diphtheria, and food poisoning. Endotoxins, which are given off after the death of bacteria, represent such normal products of bacterial metabolism as enzymes. These toxins disrupt the metabolism of biogenic amines in animals and humans. They are not specific in their effect. (See Table 1 on page 268 for data on the most important toxins.)
Bacterial toxins were discovered in 1888 by the French scientist P. Roux and the Swiss scientist A. Yersin, who obtained the toxin of the bacillus causing diphtheria (Corynaebacterium diphtheriae). This discovery made possible the development of detoxification methods that did not involve the destruction of the microorganisms producing the toxins. A successful attempt to use antitoxins (antibodies) was made in 1890 by the German bacteriologist
|Table 1. Important toxins|
|Source||Molecular weight||Dose causing death in 50% of experimental animals|
|Botulinus toxin A. . . . . . . . . .||Clostridium botulinum||150,000||2.6 × 10–8||1.7 × 10–13|
|Botulinus toxin B. . . . . . . . . .||C. botulinum||167,000||1.0 × 10–8||0.6 × 10–13|
|Tetanus toxin. . . . . . . . . .||C. tetani||140,000||2.8 × 10–8||2.0 × 10–13|
|Ricin. . . . . . . . . .||Seeds of castor-oil plant||65,000||2.8 × 10–3||4.3 × 10–8|
|Taipan toxin. . . . . . . . . .||Taipan venom||42,000||2.0 × 10–3||4.8 × 10–8|
|β-bungarotoxin. . . . . . . . . .||Krait venom||28,500||2.5 × 10–2||8.8 × 10–7|
|Cobrotoxin. . . . . . . . . .||Cobra venom||6,782||5.0 × 10–2||7.4 × 10–6|
|Toxin II. . . . . . . . . .||Scorpion venom||7,249||0.9 × 10–2||1.2 × 10–6|
E. von Behring, who established that the blood serum of animals immunized by sublethal doses of toxins possessed prophylactic and therapeutic properties. In 1924 the French scientist G. Ramon proposed a detoxification method that would preserve the immune properties of toxins; here, the toxins were treated with Formalin, as a result of which toxoids—nonpoisonous derivatives of toxins—were formed. When introduced into the organism, toxoids help to create immunity to the corresponding toxins. In the late 1950’s, with advances in protein chemistry and the development of methods for purifying and identifying proteins, it became possible not only to modify toxins selectively, but also to separate toxoids from unconverted toxins.
Toxins are also classified according to their effect on the organism. Neurotoxins act on various stages of nerve impulses. Thus, certain bacterial toxins interfere with the conductivity of nerve fibers. Taipan toxin and β-bungarotoxin act on the presynaptic membrane, suppressing the secretion of the mediator acetylcholine. Cobrotoxin and other toxins of this class (the amino acid sequence having been established for 30 of the several dozen known) block the acetylcholine receptor of the postsynaptic membrane. Cytotoxins, which are highly surface-active, destroy biological membranes. Such toxins are often encountered in snake venom; they are similar to snake neurotoxins in chemical structure but different with regard to functionally important amino acids. Cytotoxins may cause lysis of blood cells. Toxins acting as inhibitors suppress the activity of certain enzymes and thus disrupt metabolic processes. Toxins acting as enzymes (proteases, nucleases, hyaluronidases, phospholipases) destroy (hydrolyze) such important components of the organism as proteins, nucleic acids, polysaccharides, and lipids.
The use of toxins is limited to the production of toxoids. Neurotoxins are used as selectively acting agents in electrophysiologic and clinical research on the mechanics of stimulus transmission in the nervous system.
The term “toxin” is often incorrectly applied to natural non-protein substances that disrupt functions of an organism.
REFERENCESToksiny-anatoksiny i antitoksicheskie syvorotki. Moscow, 1966.
lady pchel i zmei v biologii i meditsine: Sb. st. Gorky, 1967.
Venomous and Poisonous Animals and Noxious Plants of the Pacific Region. Oxford, 1963.
Venomous Animals and Their Venoms, vols. 1–3. New York-London, 1968–71.
Microbial Toxins: A Comprehensive Treatise. Vol. 1: Bacterial Protein Toxins. New York, 1970.
Karlsson, E. “Chemistry of Some Potent Animal Toxins.” Experientia, 1973, vol. 29, no. 11, pp. 1319–27.
Zlotkin, F. “Chemistry of Animal Venoms.” Experientia, 1973, vol. 29, no. 12, pp. 1453–66.
E. IA. DEM’IASHKIN