Enterotoxin STp (E. coli) is a heat-stable enterotoxin produced by pathogenic Escherichia coli strains. Enterotoxin STp increases intracellular cGMP levels by activating guanylate cyclase in intestinal epithelial cells, thereby promoting chloride and water secretion leading to diarrhea. Enterotoxin STp can be used in research related to bacterial enteritis, diarrheal disease mechanisms, and vaccine development[1-4].
In vitro, Enterotoxin STp (0.1μM) was applied to HEK-293T cells transfected with wild-type or variant GUCY2C for 15 minutes. Enterotoxin STp increased cGMP production in cells transfected with wild-type GUCY2C and enhanced CFTR activity[5]. Enterotoxin STp (400ng/mL) was applied to mouse and porcine intestinal organoids and intestinal epithelial cell lines (MODE-K, IPEC-J2, CMT-93) for 6-72 hours. Enterotoxin STp inhibited cell proliferation, induced apoptosis, disrupted cell barrier integrity, and downregulated Wnt/β-catenin pathway activity[6].
In vivo, Enterotoxin STp (5.0mg/kg; single treatment) was administered by gavage to C57BL/6 mice. Enterotoxin STp caused small intestinal edema, disrupted intestinal integrity, induced crypt cell expansion into spheroids, and downregulated Wnt/β-catenin activity[6]. Enterotoxin STp (0.1μmol; single treatment) was administered by gavage to NHERF2-deficient mice. Enterotoxin STp lost its inhibitory effect on intestinal Na+/H+ exchanger 3 in NHERF2-deficient mice[7].
References:
[1] Yamanaka H, Fuke Y, Hitotsubashi S, et al. Functional properties of pro region of Escherichia coli heat-stable enterotoxin. Microbiol Immunol. 1993;37(3):195-205.
[2] Yamanaka H, Kameyama M, Baba T, et al. Maturation pathway of Escherichia coli heat-stable enterotoxin I: requirement of DsbA for disulfide bond formation. J Bacteriol. 1994 May;176(10):2906-13.
[3] Okamoto K, Takahara M. Synthesis of Escherichia coli heat-stable enterotoxin STp as a pre-pro form and role of the pro sequence in secretion. J Bacteriol. 1990 Sep;172(9):5260-5.
[4] Taxt A, Aasland R, Sommerfelt H, et al. Heat-stable enterotoxin of enterotoxigenic Escherichia coli as a vaccine target. Infect Immun. 2010 May;78(5):1824-31.
[5] Wolfe RM, Mohsen AW, Walsh Vockley C, et al. Novel GUCY2C variant causing familial diarrhea in a Mennonite kindred and a potential therapeutic approach. Am J Med Genet A. 2021 Jul;185(7):2046-2055.
[6] Zhou JY, Huang DG, Gao CQ, et al. Heat-stable enterotoxin inhibits intestinal stem cell expansion to disrupt the intestinal integrity by downregulating the Wnt/β-catenin pathway. Stem Cells. 2021 Apr;39(4):482-496.
[7] Chen M, Sultan A, Cinar A, et al. Loss of PDZ-adaptor protein NHERF2 affects membrane localization and cGMP- and [Ca2+]- but not cAMP-dependent regulation of Na+/H+ exchanger 3 in murine intestine. J Physiol. 2010 Dec 15;588(Pt 24):5049-63.