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''Clostridium tetani'' is a common soil bacterium and the causative agent of
tetanus Tetanus, also known as lockjaw, is a bacterial infection caused by ''Clostridium tetani'', and is characterized by muscle spasms. In the most common type, the spasms begin in the jaw and then progress to the rest of the body. Each spasm usually ...
. Vegetative cells of ''Clostridium tetani'' are usually
rod-shaped A bacillus (), also called a bacilliform bacterium or often just a rod (when the context makes the sense clear), is a rod-shaped bacterium or archaeon. Bacilli are found in many different taxonomic groups of bacteria. However, the name ''Bacill ...
and up to 2.5
μm The micrometre ( international spelling as used by the International Bureau of Weights and Measures; SI symbol: μm) or micrometer ( American spelling), also commonly known as a micron, is a unit of length in the International System of Uni ...
long, but they become enlarged and tennis racket- or drumstick-shaped when forming
spore In biology, a spore is a unit of sexual or asexual reproduction that may be adapted for dispersal and for survival, often for extended periods of time, in unfavourable conditions. Spores form part of the life cycles of many plants, algae, ...
s. ''C. tetani'' spores are extremely hardy and can be found globally in soil or in the gastrointestinal tract of animals. If inoculated into a wound, ''C. tetani'' can grow and produce a potent toxin,
tetanospasmin Tetanus toxin (TeNT) is an extremely potent neurotoxin produced by the vegetative cell of '' Clostridium tetani'' in anaerobic conditions, causing tetanus. It has no known function for clostridia in the soil environment where they are normall ...
, which interferes with motor neurons, causing tetanus. The toxin's action can be prevented with
tetanus toxoid Tetanus vaccine, also known as tetanus toxoid (TT), is a toxoid vaccine used to prevent tetanus. During childhood, five doses are recommended, with a sixth given during adolescence. After three doses, almost everyone is initially immune, but a ...
vaccines, which are often administered to children worldwide.


Characteristics

''Clostridium tetani'' is a
rod-shaped A bacillus (), also called a bacilliform bacterium or often just a rod (when the context makes the sense clear), is a rod-shaped bacterium or archaeon. Bacilli are found in many different taxonomic groups of bacteria. However, the name ''Bacill ...
,
Gram-positive bacterium In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bact ...
, typically up to 0.5 μm wide and 2.5 μm long. It is motile by way of various flagella that surround its body. ''C. tetani'' cannot grow in the presence of oxygen. It grows best at temperatures ranging from 33 to 37°C. Upon exposure to various conditions, ''C. tetani'' can shed its flagella and form a
spore In biology, a spore is a unit of sexual or asexual reproduction that may be adapted for dispersal and for survival, often for extended periods of time, in unfavourable conditions. Spores form part of the life cycles of many plants, algae, ...
. Each cell can form a single spore, generally at one end of the cell, giving the cell a distinctive drumstick shape. ''C. tetani'' spores are extremely hardy and are resistant to heat, various
antiseptics An antiseptic (from Greek ἀντί ''anti'', "against" and σηπτικός ''sēptikos'', "putrefactive") is an antimicrobial substance or compound that is applied to living tissue/skin to reduce the possibility of infection, sepsis, or putre ...
, and boiling for several minutes. The spores are long-lived and are distributed worldwide in soils as well as in the intestines of various livestock and companion animals.


Evolution

''Clostridium tetani'' is classified within the genus ''Clostridium'', a broad group of over 150 species of Gram-positive bacteria. ''C. tetani'' falls within a cluster of nearly 100 species that are more closely related to each other than they are to any other genus. This cluster includes other pathogenic ''Clostridium'' species such as '' C. botulinum'' and '' C. perfringens''. The closest relative to ''C. tetani'' is '' C. cochlearium''. Other ''Clostridium'' species can be divided into a number of genetically related groups, many of which are more closely related to members of other genera than they are to ''C. tetani''. Examples of this include the human pathogen '' C. difficile'', which is more closely related to members of genus ''
Peptostreptococcus ''Peptostreptococcus'' is a genus of anaerobic, Gram-positive, non-spore forming bacteria. The cells are small, spherical, and can occur in short chains, in pairs or individually. They typically move using cilia. ''Peptostreptococcus'' are slow- ...
'' than to ''C. tetani''.


Role in disease

While ''C. tetani'' is frequently benign in the soil or in the intestinal tracts of animals, it can sometimes cause the severe disease
tetanus Tetanus, also known as lockjaw, is a bacterial infection caused by ''Clostridium tetani'', and is characterized by muscle spasms. In the most common type, the spasms begin in the jaw and then progress to the rest of the body. Each spasm usually ...
. Disease generally begins with spores entering the body through a wound. In deep wounds, such as those from a puncture or contaminated needle injection the combination of
tissue death Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated diges ...
and limited exposure to surface air can result in a very low-oxygen environment, allowing ''C. tetani'' spores to germinate and grow. As ''C. tetani'' grows at the wound site, it releases the
toxins A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849 ...
tetanolysin Tetanolysin is a toxin produced by ''Clostridium tetani'' bacteria. Its function is unknown, but it is believed to contribute to the pathogenesis of tetanus. The other ''C. tetani'' toxin, tetanospasmin, is more definitively linked to tetanus. It ...
and
tetanospasmin Tetanus toxin (TeNT) is an extremely potent neurotoxin produced by the vegetative cell of '' Clostridium tetani'' in anaerobic conditions, causing tetanus. It has no known function for clostridia in the soil environment where they are normall ...
as cells lyse. The function of tetanolysin is unclear, although it may help ''C. tetani'' to establish infection within a wound. Tetanospasmin ("tetanus toxin") is one of the most potent toxins known, with an estimated lethal dose less than 2.5
nanogram To help compare different orders of magnitude, the following lists describe various mass levels between 10−59  kg and 1052 kg. The least massive thing listed here is a graviton, and the most massive thing is the observable universe. ...
s per kilogram of body weight, and is responsible for the symptoms of tetanus. Tetanospasmin spreads via the lymphatic system and bloodstream throughout the body, where it is taken up into various parts of the nervous system. In the nervous system, tetanospasmin acts by blocking the release of the inhibitory neurotransmitters
glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid ( carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogen ...
and gamma-aminobutyric acid at
motor nerve A motor nerve is a nerve that transmits motor signals from the central nervous system (CNS) to the muscles of the body. This is different from the motor neuron, which includes a cell body and branching of dendrites, while the nerve is made up of ...
endings. This blockade leads to the widespread activation of motor neurons and
spasm A spasm is a sudden involuntary contraction of a muscle, a group of muscles, or a hollow organ such as the bladder. A spasmodic muscle contraction may be caused by many medical conditions, including dystonia. Most commonly, it is a muscle ...
ing of muscles throughout the body. These muscle spasms generally begin at the top of the body and move down, beginning about 8 days after infection with lockjaw, followed by spasms of the abdominal muscles and the limbs. Muscle spasms continue for several weeks. The gene encoding tetanospasmin is found on a plasmid carried by many strains of ''C. tetani''; strains of bacteria lacking the plasmid are unable to produce toxin. The function of tetanospasmin in bacterial physiology is unknown.


Treatment and prevention

''Clostridium tetani'' is susceptible to a number of
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...
s, including
chloramphenicol Chloramphenicol is an antibiotic useful for the treatment of a number of bacterial infections. This includes use as an eye ointment to treat conjunctivitis. By mouth or by injection into a vein, it is used to treat meningitis, plague, cholera, a ...
,
clindamycin Clindamycin is an antibiotic medication used for the treatment of a number of bacterial infections, including osteomyelitis (bone) or joint infections, pelvic inflammatory disease, strep throat, pneumonia, acute otitis media (middle ear infect ...
, erythromycin, penicillin G, and
tetracycline Tetracycline, sold under various brand names, is an oral antibiotic in the tetracyclines family of medications, used to treat a number of infections, including acne, cholera, brucellosis, plague, malaria, and syphilis. Common side effects in ...
. However, the usefulness of treating ''C. tetani'' infections with antibiotics remains unclear. Instead, tetanus is often treated with
tetanus immune globulin Anti-tetanus immunoglobulin, also known as tetanus immune globulin (TIG) and tetanus antitoxin, is a medication made up of antibodies against the tetanus toxin. It is used to prevent tetanus in those who have a wound that is at high risk, have n ...
to bind up circulating tetanospasmin. Additionally,
benzodiazepine Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, i ...
s or muscle relaxants may be given to reduce the effects of the muscle spasms. Damage from ''C. tetani'' infection is generally prevented by administration of a tetanus vaccine consisting of tetanospasmin inactivated by formaldehyde, called tetanus toxoid. This is made commercially by growing large quantities of ''C. tetani'' in
fermenter Industrial fermentation is the intentional use of fermentation in manufacturing products useful to humans. In addition to the mass production of fermented foods and drinks, industrial fermentation has widespread applications in chemical industry ...
s, then purifying the toxin and inactivating in 40% formaldehyde for 4-6 weeks. The toxoid is generally coadministered with diphtheria toxoid and some form of pertussis vaccine as
DPT vaccine The DPT vaccine or DTP vaccine is a class of combination vaccines against three infectious diseases in humans: diphtheria, pertussis (whooping cough), and tetanus. The vaccine components include diphtheria and tetanus toxoids and either kill ...
or DTaP. This is given in several doses spaced out over months or years to elicit an immune response that protects the host from the effects of the toxin.


Research

''Clostridium tetani'' can be grown on various anaerobic growth media such as thioglycolate media, casein hydrolysate media, and
blood agar An agar plate is a Petri dish that contains a growth medium solidified with agar, used to culture microorganisms. Sometimes selective compounds are added to influence growth, such as antibiotics. Individual microorganisms placed on the plate wi ...
. Cultures grow particularly well on media at a neutral to alkaline pH, supplemented with reducing agents. The genome of a ''C. tetani'' strain has been sequenced, containing 2.80 million
base pair A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
s with 2,373 protein coding genes.


History

Clinical descriptions of tetanus associated with wounds are found at least as far back as the 4th century
BCE Common Era (CE) and Before the Common Era (BCE) are year notations for the Gregorian calendar (and its predecessor, the Julian calendar), the world's most widely used calendar era. Common Era and Before the Common Era are alternatives to the o ...
, in Hippocrates' ''
Aphorisms An aphorism (from Greek ἀφορισμός: ''aphorismos'', denoting 'delimitation', 'distinction', and 'definition') is a concise, terse, laconic, or memorable expression of a general truth or principle. Aphorisms are often handed down by tra ...
''. The first clear connection to the soil was in 1884, when
Arthur Nicolaier Arthur Nicolaier (4 February 1862 in Cosel, Upper Silesia, Prussia – 28 August 1942 in Berlin) was a German Jewish internist. Most famous for his work on discovering a cure for tetanus which was an extremely fatal disease if it wasn't treated in ...
showed that animals injected with soil samples would develop tetanus. In 1889, ''C. tetani'' was isolated from a human victim by
Kitasato Shibasaburō Baron was a Japanese physician and bacteriologist. He is remembered as the co-discoverer of the infectious agent of bubonic plague in Hong Kong during an outbreak in 1894, almost simultaneously with Alexandre Yersin. Kitasato was nominat ...
, who later showed that the organism could produce disease when injected into animals, and that the toxin could be neutralized by specific
antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
. In 1897,
Edmond Nocard Edmond Isidore Etienne Nocard (29 January 1850 – 2 August 1903), was a French veterinarian and microbiologist, born in Provins (Seine-et-Marne, France). Nocard studied veterinary medicine from 1868 to 1871 and (after a brief service in t ...
showed that tetanus antitoxin induced
passive immunity Passive immunity is the transfer of active humoral immunity of ready-made antibodies. Passive immunity can occur naturally, when maternal antibodies are transferred to the fetus through the placenta, and it can also be induced artificially, when ...
in humans, and could be used for
prophylaxis Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...
and treatment. In World War I, injection of tetanus
antiserum Antiserum is a blood serum containing monoclonal or polyclonal antibodies that is used to spread passive immunity to many diseases via blood donation (plasmapheresis). For example, convalescent serum, passive antibody transfusion from a previous ...
from horses was widely used as a prophylaxis against tetanus in wounded soldiers, leading to a dramatic decrease in tetanus cases over the course of the war. The modern method of inactivating tetanus toxin with formaldehyde was developed by
Gaston Ramon Gaston Ramon (30 September 1886 – 8 June 1963) was a French veterinarian and biologist best known for his role in the treatment of diphtheria and tetanus. He was born in Bellechaume (Yonne, France) and attended l'École vétérinaire d'Alfo ...
in the 1920s; this led to the development of the tetanus toxoid vaccine by P. Descombey in 1924, which was widely used to prevent tetanus induced by battle wounds during World War II.


References


External links


Type strain of ''Clostridium tetani'' at Bac''Dive'' - the Bacterial Diversity Metadatabase
{{Taxonbar, from=Q309471 Gram-positive bacteria Tetanus Bacteria described in 1881 tetani Pathogenic bacteria