This carries the multiplying new generations of V. cholerae bacteria out into the drinking water of the next host if proper sanitation measures are not in place.The cholera toxin (CTX or CT) is an oligomeric complex made up of six protein subunits: a single copy of the A subunit (part A), and five copies of the B subunit (part B), connected by a disulfide bond. The five B subunits form a five-membered ring that binds to GM1 gangliosides on the surface of the intestinal epithelium cells. The A1 portion of the A subunit is an enzyme that ADP-ribosylates G proteins, while the A2 chain fits into the central pore of the B subunit ring. Upon binding, the complex is taken into the cell via receptor-mediated endocytosis. Once inside the cell, the disulfide bond is reduced, and the A1 subunit is freed to bind with a human partner protein called ADP-ribosylation factor 6 (Arf6). Binding exposes its active site, allowing it to permanently ribosylate the Gs alpha subunit of the heterotrimeric G protein. This results in constitutive cAMP production, which in turn leads to the secretion of water, sodium, potassium, and bicarbonate into the lumen of the small intestine and rapid dehydration. The gene encoding the cholera toxin was introduced into V. cholerae by horizontal gene transfer. Virulent strains of V. cholerae carry a variant of a temperate bacteriophage called CTXφ.
For his work on cholera, John Snow is often regarded as the "Father of Epidemiology".The bacterium was isolated in 1854 by Italian anatomist Filippo Pacini, but its exact nature and his results were not widely known. In the same year, the Catalan Joaquim Balcells i Pascual discovered the bacterium. In 1856 António Augusto da Costa Simões and José Ferreira de Macedo Pinto, two Portuguese researchers, are believed to have done the same.Between the mid-1850s and the 1900s, cities in developed nations made massive investment in clean water supply and well-separated sewage treatment infrastructures. This eliminated the threat of cholera epidemics from the major developed cities in the world. In 1883, Robert Koch identified V. cholerae with a microscope as the bacillus causing the disease.Hemendra Nath Chatterjee, a Bengali scientist, was the first to formulate and demonstrate the effectiveness of oral rehydration salt (ORS) to treat diarrhea. In his 1953 paper, published in The Lancet, he states that promethazine can stop vomiting during cholera and then oral rehydration is possible. The formulation of the fluid replacement solution was 4 g of sodium chloride, 25 g of glucose and 1000 ml of water. Indian medical scientist Sambhu Nath De discovered the cholera toxin, the animal model of cholera, and successfully demonstrated the method of transmission of cholera pathogen Vibrio cholerae.Robert Allan Phillips, working at US Naval Medical Research Unit Two in Southeast Asia, evaluated the pathophysiology of the disease using modern laboratory chemistry techniques. He developed a protocol for rehydration.