Toxin Mediated Diarrhea in the 21st Century: The Pathophysiology of Intestinal Ion Transport in the Course of ETEC, V. cholerae and Rotavirus Infection

Abstract

An estimated 4 billion episodes of diarrhea occur each year. As a result, 2–3 million children and 0.5–1 million adults succumb to the consequences of this major healthcare concern. The majority of these deaths can be attributed to toxin mediated diarrhea by infectious agents, such as E. coli, V. cholerae or Rotavirus. Our understanding of the pathophysiological processes underlying these infectious diseases has notably improved over the last years. This review will focus on the cellular mechanism of action of the most common enterotoxins and the latest specific therapeutic approaches that have been developed to contain their lethal effects.

Site-specific N-Linked Glycosylation of Receptor Guanylyl Cyclase C Regulates Ligand Binding, Ligand-mediated Activation and Interaction with Vesicular Integral Membrane Protein 36, VIP36

“…Secretion of water into the intestinal lumen, which is necessary for the lubrication and breakdown of the bolus of food, is regulated by guanylin and uroguanylin (5). ST is a superagonist of GC-C, and the abnormally high levels of intracellular cGMP produced on ST binding to GC-C cause aberrant fluid-ion efflux, leading to diarrhea (6). It was noted some time ago that there appeared to be an inverse correlation between the incidence of colorectal cancer and secretory diarrhea caused by enterotoxigenic Escherichia coli (7), leading to the hypothesis that GC-C could also act as an anti-proliferative agent in the intestine (8,9).…”

“…Biotinylated proteins were pulled down using streptavidin-conjugated beads, and bound protein was analyzed by Western blotting using the GC-C:C8 monoclonal antibody. Lanes 1,3,5,7, and 10 represent the load, and lanes 2,4,6,8, and 9 represent the proteins associated with the streptavidin beads. Data shown in representative of experiments were repeated twice.…”

Blood Group O–Dependent Cellular Responses to Cholera Toxin: Parallel Clinical and Epidemiological Links to Severe Cholera

“…Combined, the net electrolyte loss leads to profound secretory diarrhea characteristic of cholera. 2,3 Similar to other important enteric pathogens, 4,5 blood group antigens appear to be an important determinant of the outcome of infections by V. cholerae. Blood group O individuals tend to develop more severe disease after infection with either classical or El Tor strains.…”

Bacterial Infections of the Small and Large Intestine

“…This channel is responsible for water secretion in basal conditions and under active stimulation by secretagogues [4]. In the intestine, water secretion is a passive process driven by active ion secretion, predominantly by Cl − secretion [5]. Chloride is taken up across the basolateral membrane via Na + /K + /2Cl − cotransporter type 1 (NKCC1), as an electroneutral process.…”