Enteroaggregative Escherichia coli heat-stable enterotoxin 1 (EAST1)

Enteroaggregative Escherichia coli heat-stable enterotoxin 1 (EAST1) is a 38-amino acid secretory peptide toxin produced primarily by enteroaggregative E. coli (EAEC) and other diarrheagenic strains, including enterotoxigenic (ETEC) and enterohemorrhagic E. coli (EHEC) (PMID: 8603943). Encoded by the astA gene, EAST1 is a member of the heat-stable enterotoxin family and shares significant structural and functional homology with the E. coli STa enterotoxin and the endogenous mammalian peptides guanylin and uroguanylin (PMID: 8385356, 12003040). It functions by binding to and activating the membrane-bound guanylate cyclase C (GC-C) receptor on the apical surface of intestinal epithelial cells. This activation leads to a rapid increase in intracellular cyclic guanosine monophosphate (cGMP), which subsequently triggers chloride secretion through the cystic fibrosis transmembrane conductance regulator (CFTR) and inhibits sodium absorption via the NHE3 exchanger (PMID: 35712128). The resulting accumulation of electrolytes and water in the intestinal lumen causes the watery diarrhea characteristic of EAEC and ETEC infections (PMID: 12003040). While its specific role in disease severity is sometimes debated, EAST1 is recognized as a key virulence factor in traveler's diarrhea and persistent childhood diarrhea, making it a target for diagnostic identification and the development of neutralizing anti-toxin therapies or multivalent vaccines (PMID: 35712128, 22897534).

Other names

EAggEC heat-stable enterotoxin 1Heat-stable enterotoxin 1EAST-1astA enterotoxin

Activation of the host intestinal receptor guanylate cyclase C (GC-C), which increases intracellular cGMP levels to stimulate CFTR-mediated chloride secretion and inhibit sodium absorption (PMID: 8385356, 12003040).