Cholera is caused by a bacterium known as Vibrio cholerae. There are different serogroups of Vibrio cholerae, but only two strains cause outbreaks - O1 and O139 (WHO, 2019). The deadly disease cholera is spread by drinking water or eating food contaminated with the Vibrio cholerae bacterium (CDC, 2018). The bacterium thrives in an environment of brackish water, i.e. water that is warm and salty. Vibrio cholerae produces a toxin in the small intestine, causing the deadly effects of cholera.

In a cholera epidemic, the source of contamination usually traces back to the feces of an infected person or through food washed in contaminated water (CDC, 2018). Cholera spreads rapidly in regions with inadequate sewage systems, poor water treatment, and poor sanitation/ hygiene. However, cholera is unlikely to be spread through direct contact from person-to-person. Although not every individual exposed to Vibrio cholerae will be affected, the bacterium can still pass with their feces to contaminate water and food supplies (WHO, 2019).

Vibrio cholerae enters via the fecal-oral route, from here the bacteria travels through the GI tract towards the small intestine. Before reaching their destination, the bacteria must survive the acidic conditions within the stomach and antimicrobial peptides in the small intestine (Almagro-Moreno et al., 2015). Those successful now focus on penetrating intestinal mucus using mucolytic enzymes followed by propulsion down a chemotactic gradient towards the intestinal mucosa.

Fimbriae on the bacterial surface is then used to attach to the intestinal mucosa. Next, an appendage on the surface of Vibrio cholerae cells called toxin coregulated pilus helps with colonization by binding the bacteria together to create a microcolony, thus increasing the local concentration (Krebs & Taylor, 2011). The local chemical environment at the intestinal wall causes Vibrio cholerae to activate the expression of ToxT regulatory proteins. ToxT proteins then activate the expression of genes that produce cholera toxin, the protein responsible for the symptoms of cholera (Almagro-Moreno et al., 2015).

Cholera toxin is made up of six protein subunits: a single A subunit and five B subunits, connected by a disulfide bond. The five B subunits form a five-membered ring that binds to GM1 gangliosides on the surface of intestinal epithelium cells (O’Neal et al., 2005). Next, the toxin enters via receptor-mediated endocytosis and once inside the disulfide bond is reduced. The now free A subunit binds to ADP-ribosylation factor 6, binding changes the shape of A subunit exposing its active site, allowing it to catalyse ADP-ribosylation of alpha subunits within G proteins (O’Neal et al., 2005). ADP-ribosylation causes alpha subunits to remain in its activated state. Increased alpha subunit activation leads to increased adenylate cyclase activity, which increases the concentration of cAMP to more than 100-fold over normal which leads to over-activation of protein kinase A. These active protein kinase A then phosphorylate the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel proteins, which stimulates intestinal mucosal cells to actively pump large amounts of Cl- into the intestinal lumen (O’Neal et al., 2005). H2O, Na+, K+, and HCO3− passively enter the intestinal lumen after due to the osmotic and electrical gradients created by the loss of Cl-. The combined effects result in rapid fluid loss leading to severe dehydration.

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