Encyclopedia of Ayurvedic Medicinal Plants

Kingdom: Bacteria

Division:Firmicutes

Class: Clostridia

Order:Clostridiales

Family:Clostridiaceae

Genus: Clostridium

 Species: C. tetani

          Clostridium tetani is a rod-shaped, anaerobic bacterium of the genus Clostridium. Like other Clostridium species, it is Gram-positive, and its appearance on a gram stain resembles tennis rackets or drumsticks. C. tetani is found as spores in soil or as parasites in the gastrointestinal tract of animals. C. tetani produces a potent biological toxin, tetanospasmin, and is the causative agent of tetanus.

Characteristics

C. tetani is a rod-shaped, obligate anaerobe which stains Gram positive in fresh cultures; established cultures may stain Gram negative. During vegetative growth, the organism cannot survive in the presence of oxygen, is sensitive to heat and has flagella which provide limited mobility. As the bacterium matures, it develops a terminal spore, which gives the organism its characteristic appearance. C. tetani spores are extremely hardy, and are resistant to heat and most antiseptics. The spores are distributed widely in manure-treated soils, and can also be found on human skin and in contaminated heroin.

Toxicity

C. tetani usually enters a host through a wound to the skin, it then replicates and germinates spores. Once an infection is established, C. tetani produces two exotoxins, tetanolysin and tetanospasmin. Eleven strains of C. tetani have been identified, which differ primarily in flagellar antigens and in its ability to produce tetanospasmin. The genes that produce toxin are encoded on a plasmid which is present in all toxigenic strains, and all strains that are capable of producing toxin produce identical toxins.

Tetanolysin serves no known function to C. tetani, and the reason the bacteria produce it is not known with certainty. Tetanospasmin is a neurotoxin and causes the clinical manifestations of tetanus. Tetanus toxin is generated in living bacteria, and is released when the bacteria lyses, such as during spore germination or during vegetative growth. A minimal amount of spore germination and vegetative cell growth are required for toxin production.

On the basis of weight, tetanospasmin is one of the most potent toxins known. The estimated minimum human lethal dose is 2.5 nanograms per kilogram of body weight, or 175 nanograms in a 70 kg (154 lb) human. The only toxins more lethal to humans are botulinum toxin, produced by Clostridium botulinum and the exotoxin produced by Corynebacterium diphtheriae, the causative agent of diphtheria.

Tetanospasmin is a zinc-dependent metalloproteinase, that is similar in structure to botulinum toxin, but each toxin produces quite different effects. C. tetani synthesizes tetanospasmin as a single 150kDa polypeptide progenitor toxin, that is then cleaved by a protease into two fragments; fragment A (a 50kDa "light chain") and fragment B (a 100 kDa heavy chain) which remain connected via a disulfide bridge. Cleavage of the progenitor toxin into A and B fragments can also be induced artificially with trypsin.

Toxin Action

           Tetanospasmin is distributed in the blood and lymphatic system of the host. The toxin acts at several sites within the central nervous system, including peripheral nerve terminals, the spinal cord, and brain, and within the sympathetic nervous system. The toxin is taken up into within the nerve axon and transported across synaptic junctions, until it reaches the central nervous system, where it is rapidly fixed to gangliosides at the presynaptic junctions of inhibitory motor nerve endings.