Clostridium tetani

Clostridium tetani with characteristic

'tennis racket' appearance.
Scientific classification
Kingdom: Bacteria
Phylum: Firmicutes
Class: Clostridia
Order: Clostridiales
Family: Clostridiaceae
Genus: Clostridium
Species: C. tetani
Binomial name
Clostridium tetani
Flügge, 1881

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.[1] 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, a disease characterized by painful muscular spasms that can lead to respiratory
failure and, in up to 40% of cases, death.

Contents
[hide]

 1 History
 2 Characteristics
 3 Vaccination
 4 Toxicity
o 4.1 Toxin Action
 5 Treatment
 6 References
o 6.1 Further reading
  7 External links

[edit] History
Tetanus was well known to ancient people, who recognized the relationship between wounds and
fatal muscle spasms. In 1884, Arthur Nicolaier isolated the strychnine-like toxin of tetanus from
free-living, anaerobic soil bacteria. The etiology of the disease was further elucidated in 1884 by
Antonio Carle and Giorgio Rattone, who demonstrated the transmissibility of tetanus for the first
time. They produced tetanus in rabbits by injecting their sciatic nerve with pus from a fatal
human tetanus case in that same year. In 1889, C. tetani was isolated from a human victim, by
Kitasato Shibasaburō, who later showed that the organism could produce disease when injected
into animals, and that the toxin could be neutralized by specific antibodies. In 1897, Edmond
Nocard showed that tetanus antitoxin induced passive immunity in humans, and could be used
for prophylaxis and treatment. Tetanus toxoid vaccine was developed by P. Descombey in 1924,
and was widely used to prevent tetanus induced by battle wounds during World War II.[2]

[edit] Characteristics
C. tetani is a rod-shaped, obligate anaerobe which stains Gram positive in fresh cultures;
established cultures may stain Gram negative.[1] During vegetative growth, the organism cannot
survive in the presence of oxygen, is heat-sensitive and exhibits flagellar motility. As the
bacterium matures, it develops a terminal spore, which gives the organism its characteristic
appearance. C. tetani spores are extremely hardy as they are resistant to heat and most
antiseptics.[3] The spores are distributed widely in manure-treated soils and can also be found on
human skin and in contaminated heroin.[2]

[edit] Vaccination
Tetanus can be prevented through the use of an effective vaccine, simple or adsorbed Tetanus
vaccine, combined Tetanus and Killed Polio vaccine, or the older DTP (diphtheria, tetanus,
pertussis) vaccine. Side effects are rare, but if they do occur, include:

 Fever
 Pain at the injection site
 Unexplained crying in infants, irritability in older children or adults.

Severe reactions are extremely rare and include anaphylaxis, seizures and encephalopathy. These
events are thought to occur less if only the tetanus-diphtheria component of the vaccine is
given[citation needed]. It is recommended that all infants receive the vaccine at 2, 4, 6, and 15 months
of age. A fifth booster dose should be given at 4-6 years of age. After that, it should be given
every 10 years. However, if a bite, scratch, or puncture occurs more than five years after the last
dose of vaccine, the patients should receive another dose of vaccine.
[edit] Toxicity
C. tetani usually enters a host through a wound to the skin and then it replicates. 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 their
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.[4]

Tetanolysin serves no known benefit to C. tetani. Tetanospasmin is a neurotoxin that causes the
clinical manifestations of tetanus. Tetanus toxin is generated in living bacteria, and is released
when the bacteria lyse, such as during spore germination or during vegetative growth. A minimal
amount of spore germination and vegetative cell growth are required for toxin production.[4]

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.[2] The only toxins more lethal to humans are botulinum toxin, produced
by close relative Clostridium botulinum and the exotoxin produced by Corynebacterium
diphtheriae, the causative agent of diphtheria.

Tetanospasmin is a zinc-dependent metalloproteinase that is structurally similar to botulinum

toxin but with 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 be induced
artificially by trypsin.[4]

[edit] 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 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.
[2]

The clinical manifestations of tetanus are caused when tetanus toxin blocks inhibitory impulses,
by interfering with the release of neurotransmitters, including glycine and gamma-aminobutyric
acid. This leads to unopposed muscle contraction and spasm. Characteristic features are risus
sardonicus (a rigid smile), trismus (commonly known as "lock-jaw"), and opisthotonus (rigid,
arched back). Seizures may occur, and the autonomic nervous system may also be affected.
Tetanospasmin appears to prevent the release of neurotransmitters by selectively cleaving a
component of synaptic vesicles called synaptobrevin II.[4]

[edit] Treatment
Main article: Tetanus

When a tetanus infection becomes established, treatment usually focuses on controlling muscle
spasms, stopping toxin production, and neutralizing the effects of the toxin. Treatment includes
administration of tetanus immune globulin (TIG), which comprises antibodies that inhibit tetanus
toxin (also known as tetanus antitoxins), by binding to and removing unbound tetanus toxin from
the body. Binding of the toxin to the nerve endings appears to be an irreversible event, and TIG
is ineffective at removing bound toxin. Recovery of affected nerves requires the sprouting of a
new axon terminal.[4] Large doses of antibiotics (such as metronidazole or intramuscular
doxycycline) are also given once tetanus infection is suspected in order to halt toxin production.

Prevention of tetanus includes vaccination and cleaning the primary wound. Prophylaxis is
effective in the form of a tetanus toxoid vaccine, which is given with or without passive
immunization with tetanus immune globulin. Very few cases of tetanus have occurred in
individuals with up-to-date tetanus vaccinations. DPT vaccine (diphtheria-pertussis-tetanus) is
administered in most of the world. It is given at 2, 4, 6, and 15–18 months of age, followed by a
booster before entry to school (4-6 years). This regimen provides protection from tetanus for
about 10 years, and every 10 years thereafter, a booster shot of tetanus vaccine is recommended.
[2]

Tetanus is not contagious from person to person, and is the only vaccine-preventable disease that
is infectious but not contagious. A C. tetani infection does not result in tetanus immunity, and
tetanus vaccination should be given as soon as the patient has stabilized.[2]