Tetanospasmin

Tetanospasmin is the neurotoxin produced by the vegetative spore of Clostridium tetani in anaerobic conditions, causing tetanus. It is sometimes called spasmogenic toxin or simply, tetanus toxin. C. tetani also produces the exotoxin tetanolysin, the effects of this substance are unclear.

In the human body tetanospasmin spreads through tissue spaces into the lymphatic and vascular systems. Tetanospasmin enters the nervous system by absorption at the myoneural junctions and migrates from there through the perineural spaces in nerve trunks into the central nervous system (CNS) by retrograde axonal transport. Unchecked it will bind to the gangliosides (end plates) of all nerves.

Affected neurons are stopped from releasing the inhibitory neurotransmitters GABA (gamma-aminobutyric acid) and glycine. This leads to dangerous overactivity in the muscles from the smallest stimulus or, in jargon, the failure of motor reflex responses to be inhibited from sensory stimulation. This causes generalized contractions of the agonist and antagonist musculature, termed a tetanic spasm, it can occur in a distinctive form called opisthotonos and be sufficiently severe to fracture long bones. The shorter nerves are the first to be inhibited, which leads to the characteristic early symptoms in the face and jaw, risus sardonicus and trismus.

The toxin bind to the neurons is irreversible and nerve function can only be returned by the growth of new terminals and synapses.

Tetanospasmin is a 150-kD peptide. It is made up of two parts a 100-kD heavy or B-chain and a 50-kD light or A-chain. The chains are connected by a disulfide bond. The B-chain binds to disialogangliosides (GD2 and GD1b) on the neurone membrane. The A-chain, a zinc endopeptidase, attacks the vesicle-associated membrane protein.

Tetanospasmin is used to create the toxoid used in immunization, such as the childhood DTP vaccine.




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