Clostridium novyi | |
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Scientific classification | |
Domain: | Bacteria |
Phylum: | Bacillota |
Class: | Clostridia |
Order: | Eubacteriales |
Family: | Clostridiaceae |
Genus: | Clostridium |
Species: | C. novyi |
Binomial name | |
Clostridium novyi | |
Clostridium novyi (oedematiens) a Gram-positive, endospore- forming, obligate anaerobic bacteria of the class Clostridia. It is ubiquitous, being found in the soil and faeces. It is pathogenic, causing a wide variety of diseases in humans and animals.
Growth in culture proceeds through 3 stages: Initial growth wherein no toxin is produced; vigorous growth wherein toxin is produced; and spore formation wherein endospores are formed and toxin production decreases. It is suggested that type C may be type B that forms spores more readily so does not go through the toxin-production stage.
Isolating and identifying C novyi is difficult due to its extreme anaerobic nature. Commercial kits may not be adequate. [2] [3]
It is also fastidious and difficult to culture, requiring the presence of thiols. [4]
Clostridium novyi is considered to be made up from three clades, labelled A, B and C, distinguished by the range of toxins they produce.[ citation needed ] While strains of type C were not linked to disease to laboratory animals, presence and activity of toxins in C. novyi have been linked to infection with Bacteriophages. [5] Based on toxin production, Clostridium haemolyticum has been suggested to be considered a part of C. novyi, forming a separate type D in the genus. [6] More recent 16S-rDNA studies however have suggested, that C. haemolyticus and types B and C of C. novyi may form a distinct species, closely related to Clostridium botulinum type C and D ("group III"), instead. [5]
This section is missing information about UniProt accession for all toxins.(December 2023) |
The toxins are designated by Greek letters. [7]
C novyi type | Toxins |
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A | alpha, gamma, delta, epsilon |
B | alpha, beta, zeta |
C | gamma |
The alpha-toxin of Clostridium botulinum types C and D, is similar to the C novyi beta-toxin.[ citation needed ] The A and B toxins of Clostridium difficile show homology with the alpha-toxin of C novyi as does the lethal toxin of clostridium sordellii. [8]
The alpha-toxin is characterised as lethal and necrotizing.[ citation needed ]
The type A alpha-toxin is oedematising. [9] It acts by causing morphological changes to all cell types especially endothelial cells by inhibition of signal transduction pathways, [10] resulting in the breakdown of cytoskeletal structures. [11] The cells of the microvascular system become spherical and the attachments to neighbouring cells are reduced to thin strings. This results in leakage from the capillaries, leading to oedema. The threshold concentration for this action to occur is 5 ng/ml (5 parts per billion) with 50% of cells rounded at 50 ng/ml.
The duodenum is particularly sensitive to the toxin. Injection into dogs resulted in extreme oedema of the submucosal tissues of the duodenum while leaving the stomach uninjured. Injection into the eye resulted in lesions similar to flame haemorrhages found in diabetic retinopathy. [9]
The toxin is a large 250-kDa protein the active part of which is the NH2-terminal 551 amino acid fragment. [12] Alpha-toxins are glycosyltransferases, modifying and thereby inactivating different members of the Rho and Ras subfamily of small GTP-binding proteins. [13] [14] [15] C novyi type A alpha-toxin is unique in using UDP-N-acetylglucosamine rather than UDP-glucose as a substrate. [16]
The beta-toxin is characterised as haemolytic, necrotizing lecithinase.[ citation needed ]
The gamma-toxin is characterised as haemolytic, lecithinase.[ citation needed ]
The delta-toxin is characterised as oxygen labile haemolysin.[ citation needed ]
The epsilon-toxin is characterised as lecithino-vitelin[ check spelling ] and thought to be responsible for the pearly layer found in cultures.
The zeta-toxin is characterised as haemolysin.[ citation needed ]
The type and severity of the disease caused depends on penetration of the tissues. The epithelium of the alimentary tract, in general, provides an effective barrier to penetration. However, spores may escape from the gut and lodge in any part of the body and result in spontaneous infection should local anaerobic conditions occur.[ citation needed ]
Wound infection by C novyi and many other clostridium species cause gas gangrene [17] Spontaneous infection is mostly associated with predisposing factors of hematologic or colorectal malignancies and with diabetes mellitus, [18] although Gram-negative organisms, including Escherichia coli, may lead to a gas gangrene-like syndrome in diabetic patients. This presents with cellulitis and crepitus, and may be mistaken for gas gangrene. [19] Spontaneous, nontraumatic, or intrinsic infections from a bowel source have been increasingly reported recently. [20]
Clostridium novyi has been implicated in mortality among injecting illegal drug users. [21] [22]
Symptoms are often non-specific including, colitis[ citation needed ], oedematous duodenitis[ citation needed ], and fever with somnolence[ citation needed ].
Testing is problematical with figures presented by McLauchlin and Brazier [cited above] suggesting a false negative rate of about 40% under ideal conditions. Only positive results may be regarded as reliable. In the absence of a positive test, C. novyi type A may be inferred from characterisation by clinical observation, table 2.
Table 2 | |
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Observation | Comment |
Oedema | Especially if extreme with rapid onset. In view of the sensitivity of the duodenum to the alpha-toxin, oedematous duodenum is always suspect. |
Anaerobic | Infection occurs at an anaerobic site such as the gut or salivary gland. It may also occur at a site temporarily made anaerobic by occlusion and maintained in this state by oedema. |
Gram positive | If penicillin causes remission of oedema then a Gram positive organism is the causative agent. |
Chronic infection leading to leaky capillaries may also cause retinal haemorrhages and oedema in the lower extremities leading to necrosis and gangrene. Leaky nephrons may compromise the ability of kidneys to concentrate urine leading to frequent urination and dehydration.[ citation needed ]
Gas gangrene: infectious necrotic hepatitis (black disease) [23]
Clostridium botulinum is a gram-positive, rod-shaped, anaerobic, spore-forming, motile bacterium with the ability to produce botulinum toxin, which is a neurotoxin.
Clostridium is a genus of anaerobic, Gram-positive bacteria. Species of Clostridium inhabit soils and the intestinal tract of animals, including humans. This genus includes several significant human pathogens, including the causative agents of botulism and tetanus. It also formerly included an important cause of diarrhea, Clostridioides difficile, which was reclassified into the Clostridioides genus in 2016.
Clostridioides difficile infection, 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. Antibiotics can contribute to detrimental changes in gut microbiota; specifically, they decrease short-chain fatty acid absorption which results in osmotic, or watery, diarrhea. Complications may include pseudomembranous colitis, toxic megacolon, perforation of the colon, and sepsis.
Clostridium perfringens is a Gram-positive, bacillus (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.
The Clostridia are a highly polyphyletic class of Bacillota, 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 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.
Gas gangrene is a bacterial infection that produces tissue gas 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.
Virulence factors are cellular structures, molecules and regulatory systems that enable microbial pathogens to achieve the following:
Clostridium perfringens alpha toxin is a toxin produced by the bacterium Clostridium perfringens and is responsible for gas gangrene and myonecrosis in infected tissues. The toxin also possesses hemolytic activity.
Defensin, alpha 5 (DEFA5) also known as human alpha defensin 5 (HD5) is a protein that in humans is encoded by the DEFA5 gene. DEFA5 is expressed in the Paneth cells of the ileum.
Clostridium septicum is a gram positive, spore forming, obligate anaerobic bacterium.
Clostridioides difficile toxin B (TcdB) is a cytotoxin produced by the bacteria Clostridioides difficile. It is one of two major kinds of toxins produced by C. difficile, the other being a related enterotoxin. Both are very potent and lethal.
Clostridioides difficile toxin A (TcdA) is a toxin produced by the bacteria Clostridioides difficile, formerly known as Clostridium difficile. It is similar to Clostridium difficile Toxin B. The toxins are the main virulence factors produced by the gram positive, anaerobic, Clostridioides difficile bacteria. The toxins function by damaging the intestinal mucosa and cause the symptoms of C. difficile infection, including pseudomembranous colitis.
Microbial toxins are toxins produced by micro-organisms, including bacteria, fungi, protozoa, dinoflagellates, and viruses. Many microbial toxins promote infection and disease by directly damaging host tissues and by disabling the immune system. Endotoxins most commonly refer to the lipopolysaccharide (LPS) or lipooligosaccharide (LOS) that are in the outer plasma membrane of Gram-negative bacteria. The botulinum toxin, which is primarily produced by Clostridium botulinum and less frequently by other Clostridium species, is the most toxic substance known in the world. However, microbial toxins also have important uses in medical science and research. Currently, new methods of detecting bacterial toxins are being developed to better isolate and understand these toxins. Potential applications of toxin research include combating microbial virulence, the development of novel anticancer drugs and other medicines, and the use of toxins as tools in neurobiology and cellular biology.
Clostridium butyricum is a strictly anaerobic endospore-forming Gram-positive butyric acid–producing bacillus subsisting by means of fermentation using an intracellularly accumulated amylopectin-like α-polyglucan (granulose) as a substrate. It is uncommonly reported as a human pathogen and is widely used as a probiotic in Japan, Korea, and China. C. butyricum is a soil inhabitant in various parts of the world, has been cultured from the stool of healthy children and adults, and is common in soured milk and cheeses. The connection with dairy products is shown by the name, the butyr- in butyricum reflects the relevance of butyric acid in the bacteria's metabolism and the connection with Latin butyrum and Greek βούτυρον, with word roots pertaining to butter and cheese.
Fidaxomicin, sold under the brand name Dificid among others, is the first member of a class of narrow spectrum macrocyclic antibiotic drugs called tiacumicins. 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 Clostridioides difficile with relatively little disruption to the multiple species of bacteria that make up the normal, healthy intestinal microbiota. The maintenance of normal physiological conditions in the colon may reduce the probability of recurrence of Clostridioides difficile infection.
Clostridium perfringens beta toxin is one of the four major lethal protein toxins produced by Clostridium perfringens Type B and Type C strains. It is a necrotizing agent and it induces hypertension by release of catecholamine. It has been shown to cause necrotic enteritis in mammals and induces necrotizing intestinal lesions in the rabbit ileal loop model. C. perfringens beta toxin is susceptible to breakdown by proteolytic enzymes, particularly trypsin. Beta toxin is therefore highly lethal to infant mammals because of trypsin inhibitors present in the colostrum.
Hathewaya histolytica is a species of bacteria found in feces and the soil. It is a motile, gram-positive, aerotolerant anaerobe. H. histolytica is pathogenic in many species, including guinea pigs, mice, and rabbits, and humans. H. histolytica has been shown to cause gas gangrene, often in association with other bacteria species.
Clostridium tertium is an anaerobic, motile, gram-positive bacterium. Although it can be considered an uncommon pathogen in humans, there has been substantial evidence of septic episodes in human beings. C. tertium is easily decolorized in Gram-stained smears and can be mistaken for a Gram-negative organism. However, C.tertium does not grow on selective media for Gram-negative organisms.
Clostridioides difficile is a bacterium known for causing serious diarrheal infections, and may also cause colon cancer. It is known also as C. difficile, or C. diff, and is a Gram-positive species of spore-forming bacteria. Clostridioides spp. 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 cells with a bulge at their terminal ends. 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 up to three types of toxins: enterotoxin A, cytotoxin B and Clostridioides difficile transferase. Under stress conditions, the bacteria produce spores that are able to tolerate extreme conditions that the active bacteria cannot tolerate.
The Clostridial Cytotoxin (CCT) Family is a member of the RTX-toxin superfamily. There are currently 13 classified members belonging to the CCT family. A representative list of these proteins is available in the Transporter Classification Database. Homologues are found in a variety of Gram-positive and Gram-negative bacteria.