Heat-stable enterotoxin (ST) (ST)

Heat-stable enterotoxin (ST) is a potent, cysteine-rich peptide toxin produced by enterotoxigenic Escherichia coli (ETEC), including the clinically relevant B7A strain (Svennerholm et al., 1986). It serves as a primary virulence factor by mimicking the endogenous intestinal peptides guanylin and uroguanylin to bind and activate the transmembrane receptor guanylate cyclase C (GC-C) (Lucas et al., 2010). This binding event triggers an increase in intracellular cyclic GMP (cGMP), which activates the cystic fibrosis transmembrane conductance regulator (CFTR) and inhibits the sodium-hydrogen exchanger 3 (NHE3), leading to the secretion of chloride and water into the intestinal lumen (Stein et al., 2021). The resulting secretory diarrhea is a major cause of morbidity and mortality in children in low-income countries and a leading cause of traveler's diarrhea. Therapeutic strategies targeting ST include the development of oral vaccines like ETVAX and neutralizing monoclonal antibodies designed to prevent toxin-receptor engagement (Lundgren et al., 2014). Due to its small size and structural similarity to human hormones, ST presents unique challenges for drug and vaccine development, particularly regarding immunogenicity and safety (Nygren et al., 2016).

Other names

STaHeat-stable enterotoxin aEnterotoxin ST-aSThSTpEscherichia coli heat-stable enterotoxin

Neutralization of the toxin to prevent its binding to the guanylate cyclase C (GC-C) receptor, thereby inhibiting the downstream signaling cascade that leads to fluid secretion (Lucas et al., 2010).