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|Shiga-like toxin beta subunit|
Shiga-like toxin, also known as verotoxin and verocytotoxin, is a toxin generated by some strains of Escherichia coli (but see below). It is named for its similarity to the AB5-type Shiga toxin produced by the bacteria Shigella dysenteriae (see Vero cell).
There are two types, known as SLT1 and SLT2.
In 1977, researchers in Ottawa, Ontario discovered the Shiga toxin normally produced by Shigella dysenteriae in a line of E. coli. The E. coli version of the toxin was named "verotoxin" because of its ability to kill Vero cells (African green monkey kidney cells) in culture. Shortly after, the verotoxin was referred to as Shiga-like toxin because of its similarities to Shiga toxin.
It has been suggested by some researchers that the gene coding for Shiga-like toxin comes from a toxin-converting lambdoid bacteriophage, such as H-19B or 933W, inserted into the bacteria's chromosome via transduction. Phylogenetic studies of the diversity of E. coli suggest that it may have been relatively easy for Shiga toxin to transduce into certain strains of E. coli, because Shigella is itself a subgenus of Escherichia; in fact, some strains traditionally considered E. coli (including those that produce this toxin) in fact belong to this lineage. Being closer relatives of Shigella dysenteriae than of the typical E. coli, it is not at all unusual that toxins similar to that of S. dysenteriae are produced by these strains.
As with Shiga toxin, the toxin requires highly specific receptors on the cells' surface in order to attach and enter the cell; species such as cattle, swine, and deer which do not carry these receptors may harbor toxigenic bacteria without any ill effect, shedding them in their feces, from where they may be spread to humans.
The Shiga-like toxin is associated with hemolytic-uremic syndrome.
Structure and mechanism
The toxin is a multisubunit protein made up of one molecule of A subunit (32,000 molecular weight) responsible for the toxic action of the protein, and five molecules of the B subunit (7,700 molecular weight) responsible for binding to a specific cell type.
Mechanism of action
The toxin acts on the lining of the blood vessels, the vascular endothelium. The B subunits of the toxin bind to a component of the cell membrane known as 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. When the protein is inside the cell, the A subunit interacts with the ribosomes to inactivate them. The A subunit of Shiga toxin is an N-glycosidase that modifies the RNA component of the ribosome to inactivate it and so bring a halt to protein synthesis leading to the death of the cell. The vascular endothelium has to continually renew itself, so this killing of cells leads to a breakdown of the lining and to hemorrhage.[clarification needed] The first response is commonly a bloody diarrhea. This is because Shiga toxin is usually taken in with contaminated food or water.
The toxin is effective 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 the vascular endothelium of the glomerulus. This is the filtering structure that is a key to the function of the kidney. Destroying these structures leads to kidney failure and the development of the often deadly and frequently debilitating hemolytic uremic syndrome. Food poisoning with Shiga toxin often also has effects on the lungs and the nervous system.
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- Shiga-Like Toxin I at the US National Library of Medicine Medical Subject Headings (MeSH)
- Shiga-Like Toxin II at the US National Library of Medicine Medical Subject Headings (MeSH)