Heat-labile enterotoxin of enterotoxigenic Escherichia coli (LT)

Heat-labile enterotoxin (LT) is a potent AB5-type protein toxin produced by enterotoxigenic Escherichia coli (ETEC), a leading cause of traveler's diarrhea and neonatal diarrhea in developing countries (StatPearls, 2023). The toxin consists of a single A-subunit with enzymatic activity and a pentameric B-subunit responsible for binding to GM1 ganglioside receptors on host intestinal cells (UniProt, 2024). Upon internalization, the A-subunit ADP-ribosylates the Gs alpha subunit, causing permanent activation of adenylate cyclase and a subsequent surge in cyclic AMP levels (PubMed, 2022). This signaling cascade triggers the opening of chloride channels, leading to the profuse watery diarrhea characteristic of ETEC infection. Beyond its role in pathogenesis, the B-subunit (LTB) is highly immunogenic and is utilized in vaccine development, such as in the oral vaccine Dukoral, while the whole toxin is frequently studied as a mucosal adjuvant due to its ability to enhance immune responses to co-administered antigens (EMA, 2023; Journal of Immunology, 2021).

Other names

LTE. coli heat-labile enterotoxinLT-ILT-IIHeat-labile enterotoxinLT toxinEnterotoxin LT

The B-subunit pentamer binds to GM1 ganglioside receptors on the surface of intestinal epithelial cells, facilitating the entry of the A-subunit. Once inside, the A-subunit catalyzes the ADP-ribosylation of the Gs alpha subunit of the heterotrimeric G protein, leading to the constitutive activation of adenylate cyclase. This results in elevated intracellular levels of cyclic AMP (cAMP), which activates protein kinase A and subsequently the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, causing massive secretion of water and electrolytes into the intestinal lumen.