Clostridium tetani

Clostridium tetani
Clostridium tetani, which causes tetanus, is worldwide in distribution in the soil and in the feces of horses and other animals. Several types of C tetani can be distinguished by specific flagellar antigens. All share a common O (somatic) antigen, which may be masked, and all produce the same antigenic type of neurotoxin, tetanospasmin.
Toxin
The vegetative cells of C tetani produce the toxin tetanospasmin (MW 150,000) that is cleaved by a bacterial protease into two peptides (MW 50,000 and 100,000) linked by a disulfide bond. The toxin initially binds to receptors on the presynaptic membranes of motor neurons. It then migrates by the retrograde axonal transport system to the cell bodies of these neurons to the spinal cord and brain stem. The toxin diffuses to terminals of inhibitory cells, including both glycinergic interneurons and aminobutyric acid-secreting neurons from the brain stem. The toxin degrades synaptobrevin, a protein required for docking of neurotransmitter vesicles on the presynaptic membrane. Release of the inhibitory glycine and -aminobutyric acid is blocked, and the motor neurons are not inhibited. Extremely small amounts of toxin can be lethal for humans.
Pathogenesis
C tetani is not an invasive organism. The infection remains strictly localized in the area of devitalized tissue (wound, burn, injury, umbilical stump, surgical suture) into which the spores have been introduced. The volume of infected tissue is small, and the disease is almost entirely a toxemia. Germination of the spore and development of vegetative organisms that produce toxin are aided by (1) necrotic tissue, (2) calcium salts, and (3) associated pyogenic infections, all of which aid establishment of low oxidation-reduction potential.
Clinical Findings
The incubation period may range from 4–5 days to as many weeks. The disease is characterized by tonic contraction of voluntary muscles. Muscular spasms often involve first the area of injury and infection and then the muscles of the jaw (trismus, lockjaw), which contract so that the mouth cannot be opened. Gradually, other voluntary muscles become involved, resulting in tonic spasms.
Prevention & Treatment
Prevention of tetanus depends upon (1) active immunization with toxoids; (2) proper care of wounds contaminated with soil, etc; (3) prophylactic use of antitoxin; and (4) administration of penicillin.
Surgical debridement is vitally important because it removes the necrotic tissue that is essential for proliferation of the organisms. Hyperbaric oxygen has no proved effect.
Penicillin strongly inhibits the growth of C tetani and stops further toxin production. Antibiotics may also control associated pyogenic infection.
Clostridia that Produce Invasive Infections
Many different toxin-producing clostridia (Clostridium perfringens and related clostridia) can produce invasive infection (including myonecrosis and gas gangrene) if introduced into damaged tissue. About 30 species of clostridia may produce such an effect, but the most common in invasive disease is Clostridium perfringens (90%). An enterotoxin of C perfringens is a common cause of food poisoning.
Toxins
The invasive clostridia produce a large variety of toxins and enzymes that result in a spreading infection. Many of these toxins have lethal, necrotizing, and hemolytic properties. In some cases, these are different properties of a single substance; in other instances, they are due to different chemical entities. The alpha toxin of C perfringens type A is a lecithinase, and its lethal action is proportionate to the rate at which it splits lecithin (an important constituent of cell membranes) to phosphorylcholine and diglyceride. The theta toxin has similar hemolytic and necrotizing effects but is not a lecithinase. DNase and hyaluronidase, a collagenase that digests collagen of subcutaneous tissue and muscle, are also produced.