Clostridium tetani

The most ingenious exocytosis toxins, however, come from the anaerobic bacteria Clostridium botulinum and Clostridium tetani. The former produces the seven botulinum neurotoxins (BoNTs) A-G the latter produces tetanus neurotoxin (TeNT). All eight toxins consist of a heavy (H) chain and a light (L) chain that are associated by an interchain S-S bond. The L-chains enter the cytosol of axon terminals. Importantly, BoNT L-chains mainly enter peripheral cholinergic terminals, whereas the TeNT L-chain mainly enters cerebral and spinal cord GABAergic and glycinergic terminals. The L-chains are the active domains of the toxins. They are zinc-endopeptidases and specifically split the three core proteins of exocytosis, i.e. the SNAREs (Fig. 1 inset). Each ofthe eight toxins splits a... 

Tetanus is a disease caused by the release of neurotoxins from the anaerobic, spore-forming rod Clostridium tetani. The clostridial protein, tetanus toxin, possesses a protease activity which selectively degrades the pre-synaptic vesicle protein synaptobrevin, resulting in a block of glycine and y-aminobutyric acid (GABA) release from presynaptic terminals. Consistent with the loss of neurogenic motor inhibition, symptoms of tetanus include muscular rigidity and hyperreflexia. The clinical course is characterized by increased muscle tone and spasms, which first affect the masseter muscle and the muscles of the throat, neck and shoulders. Death occurs by respiratory failure or heart failure. 

A toxin is a poisonous substance produced by some bacteria, such as Clostridium tetani, the bacteria that cause tetanus. A toxin is capable of stimulating the body to produce antitoxins, which are substances that act in the same manner as antibodies. Toxins are powerful substances, and like other antigens, they can be attenuated. A toxin that is attenuated (or weakened) but still capable of stimulating the formation of antitoxins is called a toxoid. 

Detoxification. The process by which bacterial toxins are converted to harmless toxoids. Formalin is used to detoxify the toxins of both Corynebacterium diphtheriae and Clostridium tetani. The detoxification may be performed either on the whole culture in the fermenter or on the purified toxin after fractionation. 

Altered release. Tetanus is an infectious disease caused by the bacterium Clostridium tetani. This bacterium produces a neurotoxin active on inhibitory synapses in the spinal cord. Motor neurons, which supply skeletal muscle and cause contraction, have cell bodies that lie in the spinal cord. Under normal circumstances, these motor neurons receive excitatory and inhibitory inputs from various sources. The balance of these inputs results in the appropriate degree of muscle tone or muscle contraction. Tetanus toxin prevents the release of gamma amino butyric acid (GABA), an important neurotransmitter active at these inhibitory synapses. Eliminating inhibitory inputs results in unchecked or unmodulated excitatory input to the motor neurons. The resulting uncontrolled muscle spasms initially occur in the muscles of the jaw, giving rise to the expression lockjaw. The muscle spasms eventually... 

Delayed-action neurotoxin that blocks the release of acetylcholine that is a crystalline solid obtained from bacteria (Clostridium tetani). Dried material is stable for years when stored between 39 and 45°F otherwise, it is relatively unstable and very sensitive to heat. 

Antibodies raised against venom of various spiders Specificity against toxin of Clostridium tetani Specificity against toxin of C. tetani Antibodies against tick-borne encephalitis virus Specificity for causative agent of chicken pox... 

The toxoid is then prepared by treating the active toxin produced with formaldehyde. The product is normally sold as a sterile aqueous preparation. Tetanus vaccine production follows a similar approach. Clostridium tetani is cultured in appropriate media. The toxin is recovered and inactivated by formaldehyde treatment. Again, it is usually marketed as a sterile aqueous-based product. 

Examples are diphtheria and tetanus vaccines. Diphtheria vaccine is produced by formaldehyde treatment of the toxin secreted by Corynebacterium diptheriae. Similarly, tetanus vaccine is obtained from toxins of cultured Clostridium tetani that has been treated with formaldehyde. 

Classical bacterial exotoxins, such as diphtheria toxin, cholera toxin, clostridial neurotoxins, and the anthrax toxins are enzymes that modify their substrates within the cytosol of mammalian cells. To reach the cytosol, these toxins must first bind to different cell-surface receptors and become subsequently internalized by the cells. To this end, many bacterial exotoxins contain two functionally different domains. The binding (B-) domain binds to a cellular receptor and mediates uptake of the enzymatically active (A-) domain into the cytosol, where the A-domain modifies its specific substrate (see Figure 1). Thus, three important properties characterize the mode of action for any AB-type toxin selectivity, specificity, and potency. Because of their selectivity toward certain cell types and their specificity for cellular substrate molecules, most of the individual exotoxins are associated with a distinct disease. Because of their enzymatic nature, placement of very few A-domain molecules in the cytosol will normally cause a cytopathic effect. Therefore, bacterial AB-type exotoxins which include the potent neurotoxins from Clostridium tetani and C. botulinum are the most toxic substances known today. However, the individual AB-type toxins can greatly vary in terms of subunit composition and enzyme activity (see Table 2). 

TeNT Clostridium tetani AB Adaptor proteins Enhanced neurotransmitter release Tetanus... 

Eklund, M.W., Poysky, F.T. and Habig, W.H., Bacteriophages and plasmids in Clostridium botulinum and Clostridium tetani and their relationship to production of toxins, in Simpson, L.L., ed., Botulinum Neurotoxin and Tetanus Toxin, Academic Press, New York, pp. 25-51, 1989. 

Marvaud, J.C., Raffestin, S., Gibert, M. and Popoff, M.R., Regulation of the toxinogenesis in Clostridium botulinum and Clostridium tetani, Biol. Cell, 92, 455-457, 2000. 

Figure 13.9 k soldier wounded at the Battle of Corunna (a battle in the Peninsular War) suffering simultaneous contraction of all muscles after infection with the bacterium, Clostridium tetani. Both agonist and antagonist muscles are active in this condition. The bacterium is found in the earth, especially in places where animal faeces have been present. Bacteria invade the body through a wound, especially in soldiers in battle. The bacterium secretes a toxin that is absorbed into the motor nerves which then become acutely responsive to mild stimuli. It can lead to death unless treated (from Bell 1824). The toxin is now used in cosmetic manipulation to stimulate contraction of muscles in the face to tighten the skin which removes or conceals wrinkles (Botox). 

Tetanus Clostridium tetani tetanus toxin Blocks neurotransmitter release in the brain leading to chronic contraction of muscles (See Figure 13.9)... 

Peptococcus sp. Peptostreptococcus Microaerophilic streptococci Clostridium perfringens Clostridium tetani Veillonella sp. 

Tetanus antitoxin Horse Specificity against toxin of Clostridium tetani... 

Tetanus immunoglobulin is an example of an antibody preparation used to induee passive immunization against a mierobial toxin. Tetanus (lockjaw) is an infectious disease caused by the bacterium, Clostridium tetani. Bacterial spores can commonly contaminate surface wounds and the resulting bacterial cells produce a toxin as they multiply. The toxin interferes with normal neurological function, particularly at neuromuscular junctions. The result is spasmodic contraction of muscles and, if untreated, mortality rates are high. Treatment with antibiotics and anti-toxin, however, is highly effective if administered promptly. 

Tetanus vaccines Toxoid formed by formaldehyde treatment of toxin produced by Clostridium tetani Active immunization against tetanus... 

Dedicated facilities should be used for the handling of Bacillus anthracis, of Clostridium botulinum and of Clostridium tetani until the inactivation process is accomplished. 

Tetanus. An acute, often fatal, infectious disease caused by anaerobic, spore-forming bacillus Clostridium tetani. The clinical manifestations are the result of tetanospas-min, a potent neurotoxin elaborated by the germinating spores. 

Toxins from Corynebacterium diphtheriae or Clostridium tetani are water soluble proteins, which effectively constitute the respective vaccine antigens. However, they are treated with formaldehyde to eliminate or reduce the associated toxicity to... 

---