Cholera toxin Cholera toxin sometimes abbreviated to CTX
Cholera toxin
Cholera toxin (sometimes abbreviated to CTX, Ctx, or CT) is a protein complex secreted by the bacterium Vibrio cholerae. CTX is responsible for the massive, watery diarrhea characteristic of cholera infection. The cholera toxin is an oligomeric complex made up of six protein subunits: a single copy of the A subunit (part A, enzymatic), and five copies of the B subunit (part B, receptor binding). The three-dimensional structure of the toxin was determined using X-ray crystallography by Zhang et al. in 1995
The five B subunits—each weighing 12 k. Da, form a five-membered ring. The A subunit has two important segments. The A 1 portion of the chain (CTA 1, ) is a globular enzyme while the A 2 chain (CTA 2) forms an extended alpha helix which sits snugly in the central pore of the B subunit ring. This structure is similar in shape, mechanism, and sequence to the heat-labile enterotoxin secreted by some strains of the Escherichia coli bacterium.
After entrance into intestinal epithelial cells via receptor-mediated endocytosis, the A subunit detaches and becomes activated by proteolytic cleavage, allowing it to catalyze the ADP ribosylation of the Gαs subunit of the heterotrimeric G protein resulting in constitutive c. AMP production. This in turn leads to secretion of H 2 O, Na+, K+, Cl-, and HCO 3 - into the lumen of the small intestine resulting in rapid dehydration and other factors associated with cholera, including a rice-water stool. The gene encoding the cholera toxin is introduced into V. cholerae by horizontal gene transfer. Virulent strains of V. cholerae carry a variant of lysogenic bacteriophage called CTXf or CTXφ.
Working mechanism Once secreted, the B subunit ring of CTX will bind to GM 1 gangliosides on the surface of the host's cells. After binding takes place, the entire CTX complex is internalised by the cell and the CTA 1 chain is released by the reduction of a disulfide bridge. In fact, the endosome is moved to the Golgi. The CTA 1 fragment catalyses ADP ribosylation from NAD to the regulatory component of adenylate cyclase, thereby activating it. Increased adenylate cyclase activity increases cyclic AMP (c. AMP) synthesis causing massive fluid and electrolyte efflux, resulting in diarrhea.
Cholera signs and symptoms: The primary symptoms of cholera are profuse painless diarrhea and vomiting of clear fluid. These symptoms usually start suddenly, one to five days after ingestion of the bacteria. The diarrhea is frequently described as "rice water" in nature and may have a fishy odor. An untreated person with cholera may produce 10– 20 litres of diarrhea a day with fatal results. If the severe diarrhea and vomiting are not aggressively treated it can, within hours, result in life-threatening dehydration and electrolyte imbalances. The typical symptoms of dehydration include low blood pressure, poor skin turgor (wrinkled hands), sunken eyes, and a rapid pulse
Transmission of the bacterium: Cholera is typically transmitted by either contaminated food or water. In the developed world, seafood is the usual cause, while in the developing world it is more often water. People infected with cholera often have diarrhea, and if this highly liquid stool, colloquially referred to as "rice-water, " contaminates water used by others, disease transmission may occur. The source of the contamination is typically other cholera sufferers when their untreated diarrheal discharge is allowed to get into waterways or into groundwater or drinking water supplies.
Treatment : In most cases, cholera can be successfully treated with oral rehydration therapy (ORT), which is highly effective, safe, and simple to administer. Rice-based solutions are preferred to glucose-based ones due to greater efficiency. In severe cases with significant dehydration, intravenous rehydration may be necessary. Ringer's lactate is the preferred solution, often with added potassium. Antibiotic treatments for one to three days shorten the course of the disease and reduce the severity of the symptoms. People will recover without them, however, if sufficient hydration is maintained. Doxycycline is typically used first line, although some strains of V. cholerae have shown resistance
Vaccine: A number of safe and effective oral vaccines for cholera are available. Dukoral, an orally administered, inactivated whole cell vaccine, has an efficacy of 85%, with minimal side effects. It is available in over 60 countries. However, it is not currently recommended by the Centers for Disease Control and Prevention (CDC) for most people traveling from the United States to the third world. One injectable vaccine was found to be effective for two to three years.
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