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Bezlotoxumab is a human monoclonal antibody designed for the prevention of recurrence of Clostridium difficile infections. By x-ray crystallized structure of N-terminal of TcdB, the toxin is identified to consist of three domains: a glucosyltransferase domain (GTD), a cysteine protease and a combined repetitive oligopeptide (CROP) domain.
Clostridioides difficile infection [5] (CDI or C-diff), also known as Clostridium difficile infection, is a symptomatic infection due to the spore-forming bacterium Clostridioides difficile. [6] Symptoms include watery diarrhea, fever, nausea, and abdominal pain. [1] It makes up about 20% of cases of antibiotic-associated diarrhea. [1]
Clostridioides difficile toxin A (TcdA) is a toxin produced by the bacteria Clostridioides difficile, formerly known as Clostridium difficile. [1] It is similar to Clostridioides difficile Toxin B . The toxins are the main virulence factors produced by the gram positive , anaerobic, [ 2 ] Clostridioides difficile bacteria.
Clostridioides difficile (syn. Clostridium difficile) is a bacterium known for causing serious diarrheal infections, and may also cause colon cancer. [4] [5] It is known also as C. difficile, or C. diff (/ s iː d ɪ f /), and is a Gram-positive species of spore-forming bacteria. [6]
By x-ray crystallized structure of N-terminal of Clostridioides difficile toxin B (TcdB), the toxin was identified to consist of three domains: a GTD, a cysteine protease and a combined repetitive oligopeptides, CROP domain. The CROP domain consists of four different peptide units: B1, B2, B3, and B4.
Proteolytically processed clostridial cytotoxins A (306 kDa; TC# 1.C.57.1.2) and B (269 kDa; TC# 1.C.57.1.1) are O-glycosyltransferases that modify small GTPases of the Rho family by glucosylation of threonine residues, thereby blocking the action of the GTPases as switches of signal processes such as those mediated by the actin cytoskeleton.
The Ccd and parD systems are found to be strikingly similar in terms of their structures and actions. The antitoxin protein of each system interacts with its cognate toxin to neutralise the activity of the toxin and in the process the complex of the two becomes an efficient transcription repressor. [6]
This same toxin is known as Botox and is used in cosmetic surgery to paralyze facial muscles to reduce the signs of aging; it also has numerous other therapeutic uses. Clostridium perfringens causes a wide range of symptoms, from food poisoning to cellulitis , fasciitis , necrotic enteritis and gas gangrene .
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