Bacterial Heat-Stable Enterotoxins: Translation of Pathogenic Peptides into Novel Targeted Diagnostics and Therapeutics

Abstract

Heat-stable toxins (STs) produced by enterotoxigenic bacteria cause endemic and traveler’s diarrhea by binding to and activating the intestinal receptor guanylyl cyclase C (GC-C). Advances in understanding the biology of GC-C have extended ST from a diarrheagenic peptide to a novel therapeutic agent. Here, we summarize the physiological and pathophysiological role of GC-C in fluid-electrolyte regulation and intestinal crypt-villus homeostasis, as well as describe translational opportunities offered by STs, reflecting the unique characteristics of GC-C, in treating irritable bowel syndrome and chronic constipation, and in preventing and treating colorectal cancer.

Factors other than metalloprotease are required for full virulence of French Vibrio tubiashii isolates in oyster larvae

“…Indeed, heat treatment could destroy the bacterial cell and make it non-culturable but couldn't abolish all pathogenic effectors (Fontana, 1988;Kudryashova et al, 1998;Lin et al, 2010;Shinoda & Miyoshi, 2011). Moreover, the addition of EDTA into the infection bath could partially affect protease activity Labreuche et al, 2010;Teo et al, 2003) and some bacterial properties (Kavitha et al, 2013), but not all bacterial virulence factors.…”

Escherichia coli heat-stable enterotoxins

“…Interestingly, STa and analogs inhibit the proliferation of colon cancer cells [239]. As STa was shown to undergo ligand-based receptor-mediated endocytosis in T84 cells, with the receptors recycled to the cell surface following internalization of the ligand [240], this characteristic was seen as favorable to delivering diagnostic or therapeutic drugs into colorectal carcinoma cells.…”

“…As STa was shown to undergo ligand-based receptor-mediated endocytosis in T84 cells, with the receptors recycled to the cell surface following internalization of the ligand [240], this characteristic was seen as favorable to delivering diagnostic or therapeutic drugs into colorectal carcinoma cells. In fact, STa is now studied for its possible use as antiangiogenic and antimetastasic treatments [239,241] and could also be used for imaging colon cancer cells [242]. Besides preventing and treating colorectal cancer, STa is also investigated to treat irritable bowel syndrome and chronic constipation [239].…”

“…In fact, STa is now studied for its possible use as antiangiogenic and antimetastasic treatments [239,241] and could also be used for imaging colon cancer cells [242]. Besides preventing and treating colorectal cancer, STa is also investigated to treat irritable bowel syndrome and chronic constipation [239].…”

Open Channels for Functional Bowel Disorders: Guanylate Cyclase C Agonists in IBS and CC

“…Activation of GC-C generates cyclic guanosine monophosphate (cGMP). An increase in intracellular cGMP within intestinal epithelial cells activates CFTR, increasing the secretion of Cl -and HCO 3 -into the lumen, increasing the rate of plasmalumen water flux thereby increasing stool volume [3][4][5] in a mechanism identical to the diarrhea associated with In contrast to lubiprostone [6], linaclotide may stimulate motor activity [7]; lubiprostone, but not linaclotide, augments epithelial barrier resistance [8]. In IBS-C, linaclotide but not lubiprostone affects abdominal pain apparently independently of stool frequency [9], perhaps due to the effects of cGMP on visceral sensory afferents [10,11].…”