Enterotoxigenic Escherichia coli heat-stable enterotoxin (ST) (ST)

Enterotoxigenic Escherichia coli (ETEC) heat-stable enterotoxin (ST) is a potent, low-molecular-weight peptide toxin and a primary virulence factor responsible for secretory diarrhea [1]. It is produced by ETEC strains, which are major causes of morbidity in children in low-income regions and the most common cause of traveler's diarrhea [2, 3]. ST functions by mimicking the endogenous intestinal peptides guanylin and uroguanylin to bind and activate the guanylate cyclase C (GC-C) receptor on the apical surface of enterocytes [1, 4]. This interaction triggers a signaling cascade that increases intracellular cyclic GMP, leading to massive fluid and electrolyte secretion into the bowel lumen [2]. In clinical medicine, the structure of ST has been leveraged to develop synthetic agonists like linaclotide and plecanatide for treating gastrointestinal motility disorders [4, 5]. Current drug development efforts also focus on the creation of ST-based vaccines and neutralizing antibodies to prevent ETEC infections [6]. Understanding the molecular interaction between ST and GC-C has been pivotal in both infectious disease research and the development of treatments for chronic constipation [2, 4].

Other names

STaSThSTpHeat-stable enterotoxin aETEC STEscherichia coli heat-stable enterotoxin

The heat-stable enterotoxin (ST) acts as a molecular mimic of the endogenous peptides guanylin and uroguanylin, binding to the extracellular domain of guanylate cyclase C (GC-C) [1, 2]. This binding stimulates the intrinsic catalytic activity of GC-C, converting GTP to cGMP [2]. Elevated cGMP levels activate protein kinase G II (PKG-II), which phosphorylates the cystic fibrosis transmembrane conductance regulator (CFTR), increasing chloride and bicarbonate secretion [3]. Simultaneously, cGMP inhibits the sodium-hydrogen exchanger 3 (NHE3), reducing sodium absorption [3]. The resulting osmotic gradient draws water into the intestinal lumen, causing secretory diarrhea [1, 3]. Therapeutic analogs like linaclotide utilize this same mechanism to treat constipation [4].