Clostridium is a genus of Gram-positive bacteria, which includes several significant human pathogens, including the causative agent of botulism. The genus formerly included an important cause of diarrhea, Clostridium difficile, which was separated after 16S rRNA analysis. They are obligate anaerobes capable of producing endospores. The normal, reproducing cells of Clostridium, called the vegetative form, are rod-shaped, which gives them their name, from the Greek κλωστήρ or spindle. Clostridium endospores have a distinct bowling pin or bottle shape, distinguishing them from other bacterial endospores, which are usually ovoid in shape. Clostridium species inhabit soils and the intestinal tract of animals, including humans. Clostridium is a normal inhabitant of the healthy lower reproductive tract of women.
|SE micrograph of Clostridium difficile colonies from a stool sample|
Clostridium and Bacillus are both in the phylum Firmicutes, but they are in different classes, orders, and families. Microbiologists distinguish Clostridium from Bacillus by the following features:
Clostridium and Desulfotomaculum are both in the class Clostridia and order Clostridiales, and they both produce bottle-shaped endospores, but they are in different families. Clostridium can be distinguished from Desulfotomaculum on the basis of the nutrients each genus uses (the latter requires sulfur).
The Schaeffer-Fulton stain (0.5% malachite green in water) can be used to distinguish endospores of Bacillus and Clostridium from other microorganisms. There is a commercially available polymerase chain reaction (PCR) test kit (Bactotype) for the detection of C. perfringens and other pathogenic bacteria.
In general, the treatment of clostridial infection is high-dose penicillin G, to which the organism has remained susceptible. Clostridium welchii and Clostridium tetani respond to sulfonamides. Clostridia are also susceptible to tetracyclines, carbapenems (imipenem), metronidazole, vancomycin, and chloramphenicol.
The vegetative cells of clostridia are heat-labile and are killed by short heating at temperatures above 72–75 °C. The thermal destruction of Clostridium spores requires higher temperatures (above 121.1 °C, for example in an autoclave) and longer cooking times (20 min, with a few exceptional cases of > 50 min recorded in the literature). Clostridia and Bacilli are quite radiation-resistant, requiring doses of about 30 kGy, which is a serious obstacle to the development of shelf-stable irradiated foods for general use in the retail market. The addition of lysozyme, nitrate, nitrite and propionic acid salts inhibits clostridia in various foods.
Fructooligosaccharides (fructans) such as inulin, occurring in relatively large amounts in a number of foods such as chicory, garlic, onion, leek, artichoke, and asparagus, have a prebiotic or bifidogenic effect, selectively promoting the growth and metabolism of beneficial bacteria in the colon, such as bifidobacteria and lactobacilli, while inhibiting harmful ones, such as clostridia, fusobacteria, and bacteroides.
In the late 1700s, Germany experienced a number of outbreaks of an illness that seemed connected to eating certain sausages. In 1817, the German neurologist Justinus Kerner detected rod-shaped cells in his investigations into this so-called sausage poisoning. In 1897, the Belgian biology professor Emile van Ermengem published his finding of an endospore-forming organism he isolated from spoiled ham. Biologists classified van Ermengem's discovery along with other known gram-positive spore formers in the genus Bacillus. This classification presented problems, however, because the isolate grew only in anaerobic conditions, but Bacillus grew well in oxygen.
In 1924, Ida A. Bengtson separated van Ermengem's microorganisms from the Bacillus group and assigned them to a new genus, Clostridium. By Bengtson's classification scheme, Clostridium contained all of the anaerobic endospore-forming rod-shaped bacteria, except the genus Desulfotomaculum.
Botulism is a rare and potentially fatal illness caused by a toxin produced by the bacterium Clostridium botulinum. The disease begins with weakness, blurred vision, feeling tired, and trouble speaking. This may then be followed by weakness of the arms, chest muscles, and legs. Vomiting, swelling of the abdomen, and diarrhea may also occur. The disease does not usually affect consciousness or cause a fever.Botulism can be spread in several ways. The bacterial spores which cause it are common in both soil and water. They produce the botulinum toxin when exposed to low oxygen levels and certain temperatures. Foodborne botulism happens when food containing the toxin is eaten. Infant botulism happens when the bacteria develops in the intestines and releases the toxin. This typically only occurs in children less than six months old, as protective mechanisms develop after that time. Wound botulism is found most often among those who inject street drugs. In this situation, spores enter a wound, and in the absence of oxygen, release the toxin. It is not passed directly between people. The diagnosis is confirmed by finding the toxin or bacteria in the person in question.Prevention is primarily by proper food preparation. The toxin, though not the organism, is destroyed by heating it to more than 85 °C (185 °F) for longer than 5 minutes. Honey can contain the organism, and for this reason, honey should not be fed to children under 12 months. Treatment is with an antitoxin. In those who lose their ability to breathe on their own, mechanical ventilation may be necessary for months. Antibiotics may be used for wound botulism. Death occurs in 5 to 10% of people. Botulism also affects many other animals. The word is from Latin, botulus, meaning sausage. Early descriptions of botulism date from at least as far back as 1793 in Germany.Clostridia
The Clostridia are a highly polyphyletic class of Firmicutes, including Clostridium and other similar genera. They are distinguished from the Bacilli by lacking aerobic respiration. They are obligate anaerobes and oxygen is toxic to them. Species of the class Clostridia are often but not always Gram-positive (see Halanaerobium hydrogenoformans) and have the ability to form spores. Studies show they are not a monophyletic group, and their relationships are not entirely certain. Currently, most are placed in a single order called Clostridiales, but this is not a natural group and is likely to be redefined in the future.
Most species of the genus Clostridium are saprophytic organisms found in many places in the environment, most notably the soil. However, the genus does contain some human pathogens (outlined below).
The toxins produced by certain members of the genus Clostridium are among the most dangerous known. Examples are tetanus toxin (known as tetanospasmin) produced by C. tetani and botulinum toxin produced by C. botulinum. Some species have been isolated from women with bacterial vaginosis.Notable species of this class include:
Clostridium perfringens (gangrene, food poisoning)
Clostridium difficile (pseudomembranous colitis)
Clostridium tetani (tetanus)
Clostridium botulinum (botulism)
Clostridium oedematiensHeliobacteria and Christensenella are also members of the class Clostridia.
Some of the enzymes produced by this group are used in bioremediation.Clostridiaceae
The Clostridiaceae are a family of the bacterial class Clostridia, and contain the genus Clostridium.
The family Clostridiaceae (scientific name) defined by the taxonomic outline of Bergey's Manual of Systematic Bacteriology contains as its core the genus Clostridium (sensu stricto), as well as Acetivibrio, Acidaminobacter, Alkaliphilus, Anaerobacter, Caloramator, Caloranaerobacter, Coprobacillus, Dorea, Natronincola, Oxobacter, Sarcina, Sporobacter, Thermobrachium, Thermohalobacter, and Tindallia. The previous inclusion of these additional genera in a family Clostridiaceae is based for the most part because the type species of these genera are in many cases phylogenetically related to misclassified species of the genus Clostridium.
However, with the exception of Anaerobacter, Caloramator, Oxobacter, Sarcina, and Thermobrachium, these genera fall outside the radiation of what can be considered the true family Clostridiaceae and are now regarded as belonging to other families within the low G + C, Gram-positive phylum.
This misclassification is the result of well-known problems of the current taxonomic structure of the
traditional genus Clostridium. The phylogenetic analysis of Collins (1994) was the first large-scale comparison of 16S rRNA gene sequences of species of the genus Clostridium and related taxa. The fact that the species of the genus Clostridium did not form a monophyletic group has been shown in a number of studies in which small groups of Clostridium species had been compared as far back as 1981. The comparative study of Collins (1994) and subsequent studies can be used to conclude that more than half of the species currently assigned to this genus are in fact not closely related to the type species, C. butyricum, and from a phylogenetic standpoint should not be included in a newly defined genus Clostridium.
This extensive genetic diversity of the genus Clostridium had been shown using 23S rRNA:DNA hybridization studies back in 1975 by Johnson and Francis, but the 16S rRNA gene sequence approach revealed the actual phylogenetic relationships between the species of this genus and other genera.
The genus Clostridium currently comprises 152 validly described species in nomenclature. However, on the basis of 16S rRNA gene sequence analyses, only 73 of these fall within the radiation of the type species of the genus Clostridium.Clostridioides difficile (bacteria)
Clostridioides difficile (syn. Clostridium difficile), also known as C. difficile, C. diff (), or sometimes CDF/cdf, is a species of Gram-positive spore-forming bacterium.Clostridioides are anaerobic, motile bacteria, ubiquitous in nature, and especially prevalent in soil. Its vegetative cells are rod shaped, pleomorphic, and occur in pairs or short chains. Under the microscope, they appear as long, irregular (often drumstick- or spindle-shaped) cells with a bulge at their terminal ends (forms subterminal spores). Under Gram staining, C. difficile cells are Gram-positive and show optimum growth on blood agar at human body temperatures in the absence of oxygen. C. difficile is catalase and superoxide dismutase negative, and produces two types of toxins: enterotoxin A and cytotoxin B, which disrupts cytoskeleton signal transductions in the host. When stressed, the bacteria produce spores that are able to tolerate extreme conditions that the active bacteria cannot tolerate.C. difficile may become established in the human colon; it is present in 2–5% of the adult population. Sometimes antibiotic therapy for various infections has the adverse effect of disrupting the normal balance of the gut microbiota, in which case C. difficile may opportunistically dominate, causing C. difficile infection.Clostridioides difficile infection
Clostridioides difficile infection (CDI or C-diff), also known as Clostridium difficile infection, is a symptomatic infection due to the spore-forming bacterium, Clostridioides difficile. Symptoms include watery diarrhea, fever, nausea, and abdominal pain. It makes up about 20% of cases of antibiotic-associated diarrhea. Complications may include pseudomembranous colitis, toxic megacolon, perforation of the colon, and sepsis.Clostridioides difficile infection is spread by bacterial spores found within feces. Surfaces may become contaminated with the spores with further spread occurring via the hands of healthcare workers. Risk factors for infection include antibiotic or proton pump inhibitor use, hospitalization, other health problems, and older age. Diagnosis is by stool culture or testing for the bacteria's DNA or toxins. If a person tests positive but has no symptoms, the condition is known as C. difficile colonization rather than an infection.Prevention is by hand washing, terminal room cleaning in hospital, and limiting antibiotic use. Discontinuation of antibiotics may result in resolution of symptoms within three days in about 20% of those infected. Often the antibiotics metronidazole, vancomycin or fidaxomicin will cure the infection. Retesting after treatment, as long as the symptoms have resolved, is not recommended, as the person may remain colonized. Recurrences have been reported in up to 25% of people. Some tentative evidence indicates fecal microbiota transplantation and probiotics may decrease the risk of recurrence.C. difficile infections occur in all areas of the world. About 453,000 cases occurred in the United States in 2011, resulting in 29,000 deaths. Rates of disease globally have increased between 2001 and 2016. Women are more often affected than men. The bacterium was discovered in 1935 and found to be disease-causing in 1978. In the United States, healthcare-associated infections increase the cost of care by US$1.5 billion each year.Clostridium botulinum
Clostridium botulinum is a Gram-positive, rod-shaped, anaerobic, spore-forming, motile bacterium with the ability to produce the neurotoxin botulinum.The botulinum toxin can cause a severe flaccid paralytic disease in humans and other animals and is the most potent toxin known to mankind, natural or synthetic, with a lethal dose of 1.3–2.1 ng/kg in humans.C. botulinum is a diverse group of pathogenic bacteria initially grouped together by their ability to produce botulinum toxin and now known as four distinct groups, C. botulinum groups I-IV. C. botulinum groups I-IV, as well as some strains of Clostridium butyricum and Clostridium baratii, are the bacteria responsible for producing botulinum toxin.C. botulinum is responsible for foodborne botulism (ingestion of preformed toxin), infant botulism (intestinal infection with toxin-forming C. botulinum), and wound botulism (infection of a wound with C. botulinum). C. botulinum produces heat-resistant endospores that are commonly found in soil and are able to survive under adverse conditions.C. botulinum is commonly associated with bulging canned food; bulging, misshapen cans are due to an internal increase in pressure caused by gas produced by the bacteria.Clostridium difficile
Clostridium difficile may refer to:
Clostridium difficile (bacteria), also known as C. difficile, C. diff, or sometimes CDF/cdf, a species of Gram-positive spore-forming bacteria
Clostridium difficile infection or colitis (inflammation of the large intestine) resulting from infection with Clostridium difficile bacteriaClostridium difficile toxin A
Clostridium difficile toxin A (TcdA) is a toxin generated by Clostridium difficile. It is similar to Clostridium difficile Toxin B. The toxins are the main virulence factors produced by the gram positive, anaerobic, Clostridium difficile bacteria. The toxins function by damaging the intestinal mucosa and cause the symptoms of C. difficile infection, including pseudomembranous colitis.
TcdA is one of the largest bacterial toxins known. With a molecular mass of 308 kDa, it is usually described as a potent enterotoxin, but it also has some activity as a cytotoxin. The toxin acts by modifying host cell GTPase proteins by glucosylation, leading to changes in cellular activities. Risk factors for C. difficile infection include antibiotic treatment, which can disrupt normal intestinal microbiota and lead to colonization of C. difficile bacteria.Clostridium difficile toxin B
Clostridium difficile toxin B is a toxin produced by the bacteria Clostridium difficile. C. difficile produces two major kinds of toxins that are very potent and lethal; an enterotoxin (Toxin A) and a cytotoxin (Toxin B, this protein).Clostridium enterotoxin
Clostridium enterotoxins are toxins produced by Clostridium species.Clostridial species are one of the major causes of food poisoning/gastrointestinal illnesses. They are anaerobic, gram-positive, spore-forming rods that occur naturally in the soil. Among the family are: Clostridium botulinum, which produces one of the most potent toxins in existence; Clostridium tetani, causative agent of tetanus; and Clostridium perfringens, commonly found in wound infections and diarrhea cases. The use of toxins to damage the host is a method deployed by many bacterial pathogens.
The major virulence factor of C. perfringens is the CPE enterotoxin, which is secreted upon invasion of the host gut, and contributes to food poisoning and other gastrointestinal illnesses. It has a molecular weight of 35.3kDa, and is responsible for the disintegration of tight junctions between epithelial cells in the gut. This mechanism is mediated by host claudin-3 and claudin-4 receptors, situated at the tight junctions.Clostridium enterotoxin is a nine-stranded beta sheet sandwich in shape. It has been determined that it is very similar to other spore-forming bacteria. The PFAM ID is a clenterotox. The binding site is between beta sheets eight and nine. This allows the human claudin-3,4,6,7,8 and 14 to bind but not 1,2,5, and 10. The way the protein work is it destroys the cell membrane structure of animals by binding to claudin family proteins. These are components of tight junctions of the epithelial cell membrane.Clostridium perfringens
Clostridium perfringens (formerly known as C. welchii, or Bacillus welchii) is a Gram-positive, rod-shaped, anaerobic, spore-forming pathogenic bacterium of the genus Clostridium. C. perfringens is ever-present in nature and can be found as a normal component of decaying vegetation, marine sediment, the intestinal tract of humans and other vertebrates, insects, and soil. It has the shortest reported generation time of any organism at 6.3 minutes in thioglycolate medium.C. perfringens is one of the most common causes of food poisoning in the United States, alongside norovirus, Salmonella, Campylobacter, and Staphylococcus aureus. However, it can sometimes be ingested and cause no harm.Infections due to C. perfringens show evidence of tissue necrosis, bacteremia, emphysematous cholecystitis, and gas gangrene, which is also known as clostridial myonecrosis. The toxin involved in gas gangrene is known as α-toxin, which inserts into the plasma membrane of cells, producing gaps in the membrane that disrupt normal cellular function. C. perfringens can participate in polymicrobial anaerobic infections. It is commonly encountered in infections as a component of the normal flora. In this case, its role in disease is minor.
The action of C. perfringens on dead bodies is known to mortuary workers as tissue gas. It causes extremely accelerated decomposition, and cannot be stopped by normal embalming measures. These bacteria are resistant to the presence of formaldehyde in normal concentrations.Clostridium perfringens alpha toxin
Clostridium perfringens alpha toxin is a toxin produced by the bacterium Clostridium perfringens (C. perfringens) and is responsible for gas gangrene and myonecrosis in infected tissues. The toxin also possesses hemolytic activity.Clostridium tetani
Clostridium tetani is a common soil bacterium and the causative agent of tetanus. When growing in soil, C. tetani are rod-shaped and up to 2.5 micrometers long. However, when forming spores C. tetani becomes substantially enlarged at one end, resembling tennis rackets or drumsticks. 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, which interferes with motor neurons, causing tetanus. The toxin's action can be prevented with tetanus toxoid vaccines, which are often administered to children worldwide.Clostripain
Clostripain (EC 220.127.116.11, clostridiopeptidase B, clostridium histolyticum proteinase B, alpha-clostridipain, clostridiopeptidase, Endoproteinase Arg-C) is a proteinase that cleaves proteins on the carboxyl peptide bond of arginine. It was isolated from Clostridium histolyticum. The isoelectric point of the enzyme is 4.8-4.9 (at 8°C), and optimum pH is 7.4~7.8 (against α-benzoyl-arginine ethyl ester). The composition of the enzyme is indicated to be of two chains of relative molecular mass 45,000 and 12,500.Diphtheria
Diphtheria is an infection caused by the bacterium Corynebacterium diphtheriae. Signs and symptoms may vary from mild to severe. They usually start two to five days after exposure. Symptoms often come on fairly gradually, beginning with a sore throat and fever. In severe cases, a grey or white patch develops in the throat. This can block the airway and create a barking cough as in croup. The neck may swell in part due to enlarged lymph nodes. A form of diphtheria that involves the skin, eyes, or genitals also exists. Complications may include myocarditis, inflammation of nerves, kidney problems, and bleeding problems due to low levels of platelets. Myocarditis may result in an abnormal heart rate and inflammation of the nerves may result in paralysis.Diphtheria is usually spread between people by direct contact or through the air. It may also be spread by contaminated objects. Some people carry the bacteria without having symptoms, but can still spread the disease to others. The three main types of C. diphtheriae cause different severities of disease. The symptoms are due to a toxin produced by the bacteria. Diagnosis can often be made based on the appearance of the throat with confirmation by microbiological culture. Previous infection may not protect against future infection.A diphtheria vaccine is effective for prevention and available in a number of formulations. Three or four doses, given along with tetanus vaccine and pertussis vaccine, are recommended during childhood. Further doses of diphtheria-tetanus vaccine are recommended every ten years. Protection can be verified by measuring the antitoxin level in the blood. Diphtheria can be treated with the antibiotics erythromycin or benzylpenicillin. These antibiotics may also be used for prevention in those who have been exposed to the infection. A tracheotomy is sometimes needed to open the airway in severe cases.In 2015, 4,500 cases were officially reported worldwide, down from nearly 100,000 in 1980. About a million cases a year are believed to have occurred before the 1980s. Diphtheria currently occurs most often in sub-Saharan Africa, India, and Indonesia. In 2015, it resulted in 2,100 deaths, down from 8,000 deaths in 1990. In areas where it is still common, children are most affected. It is rare in the developed world due to widespread vaccination. In the United States, 57 cases were reported between 1980 and 2004. Death occurs in 5% to 10% of those affected. The disease was first described in the 5th century BC by Hippocrates. The bacterium was identified in 1882 by Edwin Klebs.Fecal microbiota transplant
Fecal microbiota transplant (FMT), also known as a stool transplant, is the process of transplantation of fecal bacteria from a healthy individual into a recipient. FMT involves restoration of the colonic microflora by introducing healthy bacterial flora through infusion of stool, e.g. by colonoscopy, enema, orogastric tube or by mouth in the form of a capsule containing freeze-dried material, obtained from a healthy donor. The effectiveness of FMT has been established in clinical trials for the treatment of Clostridium difficile infection (CDI), whose effects can range from diarrhea to pseudomembranous colitis.
Due to an epidemic of CDI in North America and Europe, FMT has gained increasing prominence, with some experts calling for it to become first-line therapy for CDI. In 2013 a randomized, controlled trial of FMT from healthy donors showed it to be highly effective in treating recurrent C. difficile in adults, and more effective than vancomycin alone. FMT has been used experimentally to treat other gastrointestinal diseases, including colitis, constipation, irritable bowel syndrome, and neurological conditions such as multiple sclerosis and Parkinson's. In the United States, the Food and Drug Administration (FDA) has regulated human feces as an experimental drug since 2013. In the United Kingdom, FMT regulation is under the remit of the Medicines and Healthcare products Regulatory Agency.Fidaxomicin
Fidaxomicin (trade names Dificid, Dificlir, and previously OPT-80 and PAR-101) is the first member of a class of narrow spectrum macrocyclic antibiotic drugs. It is a fermentation product obtained from the actinomycete Dactylosporangium aurantiacum subspecies hamdenesis.
Fidaxomicin is minimally absorbed into the bloodstream when taken orally, is bactericidal, and selectively eradicates pathogenic Clostridium difficile with relatively little disruption to the multiple species of bacteria that make up the normal, healthy intestinal flora. The maintenance of normal physiological conditions in the colon may reduce the probability of recurrence of Clostridium difficile infection.It is marketed by Merck, which acquired Cubist Pharmaceuticals in 2015 and had in turn bought the originating company, Optimer Pharmaceuticals. It is used for the treatment of Clostridium difficile infection, which is also known as Clostridium difficile associated diarrhea, and can develop into Clostridium difficile colitis and pseudomembranous colitis.
Fidaxomicin is available in a 200 mg tablet that is administered every 12 hours for a recommended duration of 10 days. Total duration of therapy should be determined by the patient's clinical status. It is currently one of the most expensive antibiotics approved for use. A standard course costs upwards of £1350.Gas gangrene
Gas gangrene (also known as clostridial myonecrosis and myonecrosis) is a bacterial infection that produces gas in tissues in gangrene. This deadly form of gangrene usually is caused by Clostridium perfringens bacteria. About 1,000 cases of gas gangrene are reported yearly in the United States.Myonecrosis is a condition of necrotic damage, specific to muscle tissue. It is often seen in infections with C. perfringens or any of myriad soil-borne anaerobic bacteria. Bacteria cause myonecrosis by specific exotoxins. These microorganisms are opportunistic and, in general, enter the body through significant skin breakage. Gangrenous infection by soil-borne bacteria was common in the combat injuries of soldiers well into the 20th century, because of nonsterile field surgery and the basic nature of care for severe projectile wounds.Other causes of myonecrosis include envenomation by snakes of the genus Bothrops (family Viperidae), ischemic necrosis, caused by vascular blockage (e.g., diabetes type II), tumours that block or hoard blood supply, and disseminated intravascular coagulation or other thromboses.Lecithinase
Lecithinase is a type of phospholipase that acts upon lecithin.It can be produced by Clostridium perfringens, Staphylococcus aureus, Pseudomonas aeruginosa or Listeria monocytogenes . C. perfringens alpha toxin (lecithinase) causes myonecrosis and hemolysis. The lecithinase of S. aureus is used in detection of coagulase-positive strains, because of high link between lecithinase activity and coagulase activity.