Shiga toxins are a family of related toxins with two major groups, Stx1 and Stx2.
Shiga toxins expressed by genes considered to be part of the genome of lambdoid prophages.
The most common sources for Shiga toxin are the bacteria S. dysenteriae and some serotypes of Escherichia coli (STEC), which includes serotypes O157:H7, and O104:H4.
Shiga toxin type 1 and type 2 (Stx-1 and 2) are the Shiga toxins produced by some E. coli strains.
Stx-1 is identical to Stx of Shigella spp. or differs by only one amino acid.
Stx-2 shares 56% sequence identity with Stx-1.
Gene coding for Shiga-like toxin is suspected comes from a toxin-converting lambdoid bacteriophage, such as H-19B or 933W, inserted into the bacteria’s chromosome via transduction.
Shigella is itself a subgenus of Escherichia; in fact, some strains, so that toxins similar to that of S. dysenteriae are produced by these strains.
The toxin requires highly specific receptors on the cells’ surface to attach and enter the cell.
Cattle, swine, and deer do not have these receptors may harbor toxigenic bacteria without any ill effect, shedding them in their feces, from where they may be spread to humans.
Symptoms of Shiga toxin ingestion: abdominal pain as well as watery diarrhea, and severe life-threatening cases are characterized by hemorrhagic colitis.
The toxin is associated with hemolytic-uremic syndrome.
The toxin act against small blood vessels, such as found in the digestive tract, the kidney, and lungs, but not against large vessels such as the arteries or major veins.
A specific target for the toxin appears to be the vascular endothelium of the glomerulus, destroying these structures leads to kidney failure and the development of the hemolytic uremic syndrome.
Food poisoning with Shiga toxin often also has effects on the lungs and the nervous system.
The B subunits of the toxin bind to a component of the cell membrane known: glycolipid globotriaosylceramide (Gb3).
Binding of the subunit B to Gb3 causes induction of narrow tubular membrane invaginations, which drives formation of inward membrane tubules for the bacterial uptake into the cell.
These tubules are essential for uptake into the host cell.
The Shiga toxin is transferred to the cytosol via Golgi network and endoplasmic reticulum (ER).
Shiga toxins inhibit protein synthesis.
Shiga toxins act on the lining of the blood vessels, the vascular endothelium, a breakdown of the lining and hemorrhage eventually occurs.
The first response is commonly a bloody diarrhea as the Shiga toxin is usually taken in with contaminated food or water.
The toxin has two subunits—designated A and B.
The B subunit is a pentamer that binds to specific glycolipids on the host cell, specifically globotriaosylceramide (Gb3).
Gb3 is, for unknown reasons, present in greater amounts in renal epithelial tissues, to which the renal toxicity of Shiga toxin may be attributed.
Gb3 is also found in central nervous system neurons and endothelium, which may lead to neurotoxicity.
Stx-2 is also known to increase the expression of its receptor GB3 and cause neuronal dysfunctions.
Shiga toxin 1 and Shiga toxin 2 have different implications.
Shiga toxin 2 produces serotypes that are much more virulent than Shiga toxin 1 producing serotypes, which rarely lead to HUS unless they also produce Shiga toxin 2.