Enterotoxigenic Escherichia coli heat-labile toxin (LT)

Enterotoxigenic Escherichia coli heat-labile toxin (LT) is a potent AB5-type protein exotoxin produced by ETEC, a leading cause of secretory diarrhea in children in developing countries and traveler's diarrhea worldwide. Structurally and functionally similar to cholera toxin (CT), LT consists of a catalytic A-subunit and a pentameric B-subunit that mediates binding to GM1 gangliosides on the surface of intestinal epithelial cells. Once internalized, the A-subunit ADP-ribosylates the Gs-alpha subunit of G proteins, causing persistent activation of adenylate cyclase and an overproduction of cyclic AMP. This signaling cascade leads to the efflux of chloride ions and water into the intestinal lumen, resulting in profuse watery diarrhea. Due to its potent immunomodulatory properties, LT and its non-toxic derivatives are extensively studied as mucosal adjuvants and are primary targets for vaccine development, including oral formulations that provide cross-protection against cholera.

Other names

Heat-labile enterotoxinE. coli heat-labile toxinLT-ILT-IILT enterotoxinLTB (B-subunit)LTA (A-subunit)

The toxin's B-subunit pentamer binds to GM1 ganglioside receptors on intestinal epithelial cells, facilitating the entry of the A-subunit. Inside the cell, the A-subunit acts as an ADP-ribosyltransferase, covalently modifying the Gs-alpha subunit of the heterotrimeric G protein. This results in the constitutive activation of adenylate cyclase, leading to a massive increase in intracellular cyclic AMP (cAMP) levels, which triggers the opening of chloride channels (CFTR) and inhibits sodium absorption, causing watery diarrhea.