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. 2019 Jan 8;11(1):24.
doi: 10.3390/toxins11010024.

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

Free PMC article

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

Haixiu Wang et al. Toxins (Basel). .
Free PMC article


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.

Keywords: ETEC; heat-stable enterotoxins; vaccination strategies.

Conflict of interest statement

The authors declare no competing interests.


Figure 1
Figure 1
Secretion of heat-stable enterotoxins by ETEC. (a) The sequences of mature STa and STb peptides and the dashed lines shown in the heat-stable enterotoxin (ST) peptides represent the disulfide bonds. (b) Synthesis and secretion of STa and STb. Sec: Secretory pathway; DsbA: Disulfide oxidoreductase.
Figure 2
Figure 2
Schematic mechanisms of heat-stable enterotoxins on enterocytes and the intestinal immune system. (a): The impact of STs on apical membranes; (b): The impact of STs on transepithelial dendrites; (c): The paracellular transport of STs. GC-C: Guanylate cyclase C; CFTR: Cystic fibrosis transmembrane conductance regulator; NHE3: Na+/H+ exchanger; PKA: cAMP-dependent protein kinase; PKGII: cGMP-dependent protein kinase II; PDE3: cGMP-inhibitable phosphodiesterase 3; Gαi3: pertussis Toxin-sensitive GTP-binding regulatory protein; A2: Phospholipases A2; C: Phospholipases C; PGE2: Prostaglandin E2; 5-HT: 5-hydroxytryptamine; CaMKII: Calmodulin-dependent protein kinase II; MMP1: Matrix metallopeptidase 1; TJs: Tight junctions.

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