Mostly bacteria do not survive in the acidic environment of the human being. These surveying bacteria exit the stomach and reach the small intestine they must propel themselves through the thick mucus that lines the small intestine to reach the intestinal walls where they can attach and thrive. Once the cholera bacteria enters the intestinal wall they are not dependendant on flagella for locomotion. The bacteria stop producing the protein flagellin to conserve energy and nutrients by changing the mix of proteins that they express in response to the changed chemical surroundings. The toxic proteins produces by the vibrio cholera produces the watery diarrhoea. This carries the multiplying new generations of V. cholera bacteria out into the drinking water of the next host if proper sanitation measures are not in place.
The cholera toxin is an oligomeic compound made up of six protein subunits a single copy of the subunit A and five copies of the subunit B connected by the disulfide bond. 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.
The cholera toxins interacts with the host cell and enhances the pumping of chloride ions into the small intestine, creating an ionic pressure which prevents sodium ions from entering the cell. The combination of sodium and chloride ions results in salt water environment in the small intestine which increases the osmosis reaction pull up to six litres of water per dat through the intestinal cells, creating the massive amounts of diarrhoes. The host can become rapidly dehydrated unless treated properly.
By inserting separate, successive sections of V. cholerae DNA into the DNA of other bacteria, such as E.coli that would not naturally produce the protein toxins, researchers have investigated the mechanisms by which V. cholerae responds to the changing chemical environments of the stomach, mucous layers, and intestinal wall. Researchers have discovered a complex cascade of regulatory proteins controls expression of V. cholerae virulence determinants.In responding to the chemical environment at the intestinal wall, the V. cholerae bacteria produce the TcpP/TcpH proteins, which, together with the ToxR/ToxS proteins, activate the expression of the ToxT regulatory protein. ToxT then directly activates expression of virulence genes that produce the toxins, causing diarrhea in the infected person and allowing the bacteria to colonize the intestine. Currentresearch aims at discovering "the signal that makes the cholera bacteria stop swimming and start to colonize that is, adhere to the cells of the small intestine."