| Clostridium tetani | |
|---|---|
 | |
| Clostridium tetani forming spores | |
Scientific classification | |
| Domain: | Bacteria |
| Kingdom: | Bacillati |
| Phylum: | Bacillota |
| Class: | Clostridia |
| Order: | Eubacteriales |
| Family: | Clostridiaceae |
| Genus: | Clostridium |
| Species: | C. tetani |
| Binomial name | |
| Clostridium tetani Flügge, 1881 | |
Clostridium tetani is a common soil bacterium and the causative agent oftetanus. Vegetative cells ofClostridium tetani are usuallyrod-shaped and up to 2.5μm long, but they become enlarged andtennis racket- or drumstick-shaped when formingspores.C. tetani spores are extremely hardy and can be found globally in soil or in thegastrointestinal tract of animals. If inoculated into a wound,C. tetani can grow and produce a potent toxin,tetanospasmin, which interferes with motor neurons, causing tetanus. The toxin's action can be prevented withtetanus toxoid vaccines, which are often administered to children worldwide.
Clostridium tetani is arod-shaped,Gram-positive bacterium, typically up to 0.5 μm wide and 2.5 μm long.[1] It is motile by way of variousflagella that surround its body.[1]C. tetanicannot grow in the presence of oxygen.[1] It grows best at temperatures ranging from 33 to 37 °C.[1]
Upon exposure to various conditions,C. tetani can shed its flagellums and form aspore.[1] Each cell can form a single spore, generally at one end of the cell, giving the cell a distinctive drumstick shape.[1]C. tetani spores are extremely hardy and are resistant to heat, variousantiseptics, and boiling for several minutes.[2] The spores are long-lived and are distributed worldwide in soils as well as in the intestines of various livestock and companion animals.[3]
Clostridium tetani is classified within the genusClostridium, a broad group of over 150 species of Gram-positive bacteria.[3]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.[3] This cluster includes other pathogenicClostridium species such asC. botulinum andC. perfringens.[3] The closest relative toC. tetani isC. cochlearium.[3] OtherClostridium 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 toC. tetani.[3] Examples of this include the human pathogenC. difficile, which is more closely related to members of genusPeptostreptococcus than toC. tetani.[4]
WhileC. tetani is frequently benign in the soil or in the intestinal tracts of animals, it can sometimes cause the severe diseasetetanus. Disease generally begins with spores entering the body through a wound.[5] In deep wounds, such as those from a puncture or contaminated needle injection, the combination oftissue death and limited exposure to surface air can result in a very low-oxygen environment, allowingC. tetani spores togerminate and grow.[2] AsC. tetani grows at the wound site, it releases thetoxinstetanolysin andtetanospasmin as cells lyse.[1] The function of tetanolysin is unclear, although it may helpC. tetani to establish infection within a wound.[6][1] Tetanospasmin ("tetanus toxin") is a potent toxin with an estimated lethal dose less than 2.5nanograms per kilogram of body weight, and is responsible for the symptoms of tetanus.[6][1] Tetanospasmin spreads via thelymphatic system and bloodstream throughout the body, where it is taken up into various parts of thenervous system.[6] In the nervous system, tetanospasmin acts by blocking the release of the inhibitoryneurotransmittersglycine andgamma-aminobutyric acid atmotor nerve endings.[5] This blockade leads to the widespread activation ofmotor neurons andspasming of muscles throughout the body.[6] These muscle spasms generally begin at the top of the body and move down, beginning about 8 days after infection withlockjaw, followed by spasms of the abdominal muscles and the limbs.[5][6] Muscle spasms continue for several weeks.[6]
The gene encoding tetanospasmin is found on aplasmid carried by many strains ofC. tetani; strains of bacteria lacking the plasmid are unable to produce toxin.[1][5] The function of tetanospasmin in bacterial physiology is unknown.[1]
Clostridium tetani is susceptible to a number ofantibiotics, includingchloramphenicol,clindamycin,erythromycin,penicillin G, andtetracycline.[3] However, the usefulness of treatingC. tetani infections with antibiotics remains unclear.[1] Instead, tetanus is often treated withtetanus immune globulin to bind up circulating tetanospasmin.[6] Additionally,benzodiazepines ormuscle relaxants may be given to reduce the effects of the muscle spasms.[1]
Damage fromC. tetani infection is generally prevented by administration of atetanus vaccine consisting of tetanospasmin inactivated byformaldehyde, called tetanus toxoid.[1] This is made commercially by growing large quantities ofC. tetani infermenters, then purifying the toxin and inactivating in 40% formaldehyde for 4–6 weeks.[1] The toxoid is generally coadministered withdiphtheria toxoid and some form ofpertussis vaccine asDPT vaccine orDTaP.[6] 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.[6]
Clostridium tetani can be grown on various anaerobicgrowth media such asthioglycolate media,casein hydrolysate media, andblood agar.[1] Cultures grow particularly well on media at a neutral to alkaline pH, supplemented withreducing agents.[1] The genome of aC. tetani strain has been sequenced, containing 2.80 millionbase pairs with 2,373 protein coding genes.[7]
Clinical descriptions of tetanus associated with wounds are found at least as far back as the 4th centuryBCE, inHippocrates'Aphorisms.[8] The first clear connection to the soil was in 1884, whenArthur Nicolaier showed that animals injected with soil samples would develop tetanus.[6] In 1889,C. tetani was isolated from a human victim byKitasato Shibasaburō, who later showed that the organism could produce disease when injected into animals, and that the toxin could be neutralized by specificantibodies. During 1890, it was found that the effects of inoculation of the organism in human body was due to chemical products at immediate vicinity of point of inoculation. Later, it was only during First World War that recognized the merits of tetanus anti toxin and theory ofKitasato Shibasaburō. In 1897,Edmond Nocard showed that tetanus antitoxin inducedpassive immunity in humans, and could be used forprophylaxis and treatment.[6] InWorld War I, injection of tetanusantiserum 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.[9] The modern method of inactivating tetanus toxin with formaldehyde was developed byGaston Ramon 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.[6]
