How do the toxins produced by cholera cause diarrhoea?
Cholera is an acute enteric disease characterized by profuse watery diarrhea. The causative agent, Vibrio cholerae, produces two toxins, cholera toxin (CT) and heat-labile toxin (LT). These toxins disrupt the normal function of the small intestine, resulting in the secretion of large amounts of chloride and water into the intestinal lumen.
Cholera toxin (CT) is the main virulence factor of V. cholerae. It is a single polypeptide with a molecular weight of approximately 84 kDa. CT is composed of two subunits, A and B. The A subunit is responsible for the toxic activity of CT, while the B subunit is responsible for binding to the cell surface and facilitating the entry of the A subunit into the cell.
LT is structurally and functionally similar to CT. However, LT is heat-labile and can be inactivated by heating at 60°C for 30 minutes. LT also has a somewhat lower molecular weight, approximately 28 kDa. CT and LT act by raising the level of cAMP, the "second messenger" of many hormones such as adrenaline.
When CT or LT binds to the intestinal epithelial cells, it activates the enzyme adenylate cyclase, which leads to an increase in the intracellular concentration of cAMP. cAMP then activates the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, resulting in the secretion of chloride ions into the intestinal lumen. Water follows the chloride ions, resulting in profuse watery diarrhea.
In addition to CT and LT, V. cholerae also produces a number of other virulence factors that contribute to the pathogenesis of cholera. These include:
* Colonization factors: These factors allow V. cholerae to attach to the intestinal epithelium.
* Toxins: V. cholerae produces a number of other toxins, including hemolysin, cytotoxin, and enterotoxin. These toxins can damage the intestinal epithelium and contribute to the symptoms of cholera.
* Biofilm formation: V. cholerae can form biofilms, which are communities of bacteria that are attached to a surface. Biofilms can help V. cholerae to survive in the environment and to resist antimicrobial agents.
Cholera is a serious disease that can lead to dehydration and electrolyte imbalance. If left untreated, cholera can be fatal. However, cholera can be effectively treated with oral rehydration therapy (ORT). ORT involves replacing the fluids and electrolytes that are lost through diarrhea. ORT can be used to treat cholera in both children and adults.