Shiga Toxin-Producing Escherichia Coli (STEC)

Infections caused by specific strains of Shiga toxin-producing Escherichia coli (STEC), especially enterohemorrhagic variants, can lead to severe extraintestinal complications, such as acute renal failure, posing a significant public health concern worldwide. The main culprits behind the clinical manifestations of STEC infections are the highly cytotoxic Shiga toxins (Stxs). These toxins, classified as class II ribosome-inactivating proteins, are the primary virulence factors responsible for the development of key clinical symptoms associated with Stx-mediated pathogenesis, including bloody diarrhea, hemolytic uremic syndrome (HUS), and neurological complications.

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Introduction to STEC

Escherichia coli is a bacterium commonly found in the gastrointestinal tract of mammals and birds. While most strains of E. coli are harmless, certain types have been linked to gastrointestinal diseases in both humans and animals. There are six main groups of pathogenic E. coli based on their specific characteristics: Shiga toxin-producing E. coli (STEC or VTEC or EHEC), enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), enteroinvasive E. coli (EIEC), and diffusely adherent E. coli (DAEC). Among these, STEC is a distinct group known for its production of potent cytotoxins that disrupt protein synthesis in eukaryotic cells. These toxins are known as verocytotoxins (VT) or Shiga toxins (Stx) because they resemble the toxin produced by Shigella dysenteriae.

Within the category of STEC, there is a subset called enterohaemorrhagic E. coli (EHEC). This group of STEC serotypes has been strongly associated with bloody diarrhea and a serious condition called HUS in developed countries. While the majority of severe cases are caused by O157:H7 serotype strains, there has been an increasing number of reported infections caused by non-O157 serogroups such as O26, O111, O103, and O145. These non-O157 strains are now commonly referred to as non-O157 EHEC.

Figure 1. Number of STEC O157 and non-O157 outbreaks by year, United States, 2010–2017.
(Source: Tack, D. M. et al., 2021)

Mechanism of Action

• Attaching and Effacing Adhesion: Most STEC included in the EHEC group have a unique ability to colonize the intestinal mucosa by subverting the normal function of epithelial cells. This colonization leads to a characteristic histopathological lesion known as "attaching and effacing" (A/E). The A/E lesion is characterized by changes in the cell structure, including the loss of microvilli and close adherence between the bacteria and the epithelial cell membrane. This adherence is facilitated by the accumulation of polymerized actin beneath the adherent bacteria.
• Production of Virulence Factors: STEC strains produce virulence factors, which can directly damage the cells lining the intestine. They are internalized by intestinal cells and inhibit protein synthesis, leading to cell death.
• Local Tissue Damage: The damaged intestinal cells result in the disruption of the intestinal barrier, leading to increased permeability and leakage of fluids and blood into the gut lumen. This contributes to the characteristic bloody diarrhea observed in STEC infection.
• Systemic Effects: In some cases, the released virulence factors can enter the bloodstream and reach distant organs, particularly the kidneys. The toxins can damage the endothelial cells lining the blood vessels, leading to a cascade of events that can result in HUS.
• Inflammatory Response: The infection triggers an inflammatory response in the intestine, leading to the recruitment of immune cells and the release of inflammatory mediators. This immune response aims to clear the infection but can also contribute to tissue damage and inflammation-associated symptoms.