Sunday 15 March 2009
Tetanus, also called lockjaw, is a medical condition characterized by a prolonged contraction of skeletal muscle fibers. The primary symptoms are caused by tetanospasmin, a neurotoxin produced by the Gram-positive, obligate anaerobic bacterium Clostridium tetani.
Infection generally occurs through wound contamination, and often involves a cut or deep puncture wound. As the infection progresses, muscle spasms in the jaw develop, hence the name lockjaw. This is followed by difficulty in swallowing and general muscle stiffness and spasms in other parts of the body. Infection can be prevented by proper immunization and by post-exposure prophylaxis.
C. tetani also produces the exotoxin tetanolysin, the effects of which are as yet unclear.
Tetanospasmin is the neurotoxin produced by the vegetative spore of Clostridium tetani in anaerobic conditions, causing tetanus. It has no known function for clostridia in the soil environment where they are normally encountered. It is sometimes called spasmogenic toxin, tetanus toxin or abbreviated to TeTx or TeNT.
Tetanospasmin spreads through tissue spaces into the lymphatic and vascular systems. It enters the nervous system at the neuromuscular junctions and migrates through nerve trunks and into the central nervous system (CNS) by retrograde axonal transport.
The peptide tetanospasmin has a molecular weight of 150kDa. It is made up of two parts: a 100kDa heavy or B-chain and a 50kDa 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 vesicle-associated membrane proteins (VAMPs).
The action of the A-chain stops the affected neurons from releasing the inhibitory neurotransmitters GABA (gamma-aminobutyric acid) and glycine by degrading the protein synaptobrevin. The consequence of this is dangerous overactivity in the muscles from the smallest stimulus, the failure of inhibition of motor reflexes by sensory stimulation. This causes generalized contractions of the agonist and antagonist musculature, termed a tetanic spasm.