Choleratoksiinis

Choleratoksiinis, known in English as cholera toxin, is a potent enterotoxin produced by the bacterium Vibrio cholerae, the agent responsible for cholera. It is an AB5 toxin composed of one enzymatic A subunit connected to a disulfide-linked A2 segment and a pentamer of B subunits. The B subunits bind the GM1 ganglioside receptor on the surface of intestinal epithelial cells, allowing the toxin complex to enter the cell.

Once inside, the A1 fragment is translocated into the cytosol and catalyzes ADP-ribosylation of the Gs alpha subunit of heterotrimeric G proteins. This modification locks adenylate cyclase in an active state, causing a sustained rise in intracellular cAMP. Elevated cAMP triggers chloride secretion through the CFTR channel and impairs sodium chloride absorption, leading to massive, watery diarrhea often described as rice-water stools. The toxin acts indirectly on enterocytes to cause fluid loss rather than directly killing cells.

Genetics and distribution: The ctxAB toxin genes are carried by the CTXφ filamentous phage integrated into the Vibrio cholerae genome. Expression is regulated by the ToxR/ToxS regulatory system among others. Cholera is most commonly associated with V. cholerae serogroups O1 and O139; non-O1/non-O139 strains may be toxigenic but are less frequently associated with pandemic disease.

Diagnosis and treatment: Diagnosis relies on clinical presentation supported by laboratory detection of the toxin or ctxAB genes or identification of V. cholerae in stool. Management emphasizes rapid rehydration and electrolyte replacement, often with oral rehydration solutions, and zinc supplementation. Antibiotics can shorten illness duration and bacterial shedding. Vaccines are available, including oral killed vaccines that provide protection against O1 and, to varying extents, O139.

Prevention focuses on access to clean water, sanitation, and hygiene to reduce transmission.