Heat-Stable Enterotoxins of Enterotoxigenic Escherichia coli and Their Impact on Host Immunity

Abstract

Enterotoxigenic Escherichia coli (ETEC) are an important diarrhea-causing pathogen and are regarded as a global threat for humans and farm animals. ETEC possess several virulence factors to infect its host, including colonization factors and enterotoxins. Production of heat-stable enterotoxins (STs) by most ETEC plays an essential role in triggering diarrhea and ETEC pathogenesis. In this review, we summarize the heat-stable enterotoxins of ETEC strains from different species as well as the molecular mechanisms used by these heat-stable enterotoxins to trigger diarrhea. As recently described, intestinal epithelial cells are important modulators of the intestinal immune system. Thus, we also discuss the impact of the heat-stable enterotoxins on this role of the intestinal epithelium and how these enterotoxins might affect intestinal immune cells. Finally, the latest developments in vaccination strategies to protect against infections with ST secreting ETEC strains are discussed. This review might inform and guide future research on heat-stable enterotoxins to further unravel their molecular pathogenesis, as well as to accelerate vaccine design.

Synbiotic Effects of Enzyme and Probiotics on Intestinal Health and Growth of Newly Weaned Pigs Challenged With Enterotoxigenic F18+Escherichia coli

“…The predisposition of newly weaned pigs to PWD caused by ETEC have been related to the psychological, environmental, and physiological stress after weaning, as well as sudden transition from sow's milk to plant-based diets that are solid and less digestible. These stressors disrupt the immune system and the intestinal microbiota leading to intestinal inflammation and PWD ( 41 , 42 ), consequently reducing growth performance ( 5 , 6 , 17 ). As previously reported ( 31 , 43 ), the challenge with E. coli F18 + in this study reduced growth and feed efficiency without affecting feed intake, which is in agreement with previous studies.…”

“…The ETEC slightly reduced the microbial diversity index but caused an imbalance in jejunal mucosa-associated microbiota by increasing the relative abundance of Proteobacteria by increasing the family Helicobacteraceae and the genus Helicobacter , consequently reducing the relative abundance of Bacteroidetes and Firmicutes, Prevotellaceae , and Mitsukella and Selenomonas , as previously reported by Bin et al ( 69 ) and Pollock et al ( 70 ). The adherence of the ETEC and the production of enterotoxins with the subsequent secretion of fluid to the intestinal lumen ( 41 , 51 ) create a propitious environment to the growth of proteobacteria ( 17 ). The high abundance of Helicobacteraceae which belong to the Proteobacteria has been reported to cause a reduction of the mucous layer protection ( 65 ), which explains the impact of the challenge on the villus height, immune response, and the oxidative stress status, whereas, Prevotellaceae , which belongs to the Bacteroidetes has been related to intestinal mucosa of healthy pigs fed plant-based diets ( 71 , 72 ).…”

Comprehensive mapping of the cell response to E. coli infection in porcine intestinal epithelial cells pretreated with exopolysaccharide derived from Lactobacillus reuteri

“…ETECs adhere to epithelial cells through the interaction of fimbrial and non-fimbrial adhesins with cell surface receptors. Upon attachment, they release LT and/or ST enterotoxins, which act upon intestinal enterocytes by disrupting electrolyte homeostasis, resulting in fluid loss and eventually secretory diarrhea [37,38]. LTs activate adenylate cyclase, which substantially increases the intracellular concentration of cAMP [39].…”

Multisite Controlled Blinded Field Studies to Evaluate the Effect of an Oral Live Escherichia Coli Bivalent F4/F18 Vaccine in Pig Nurseries with Mild Cases of Post-Weaning Diarrhea or Subclinical ETEC Infections.

“…coli enterotoxins harbor functions beyond uid and electrolyte hypersecretion that can impair the gut health. As examples, STb is able to alter the tight junction complexes that increases the permeability of the intestinal epithelium and might modulate innate immune responses, while STa enhances the secretion of pro-in ammatory cytokines and chemokines in the small intestinal lumen (Wang et al, 2019.). ETEC infection is also associated with an important microbiota change in the distal small intestines but not in the feces (Pollock et al, 2019).…”