Shiga toxin

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Shiga toxin

Shiga toxins are a family of related toxin

Exotoxin

An exotoxin is a toxin excreted by a microrganism, including bacterium, fungi, algae, and protozoa. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism....
s with two major groups, Stx1 and Stx2, whose genes are considered to be part of the genome

Genome

In classical genetics, the genome of a diploid organism including eukarya refers to a full set of chromosomes or genes in a gamete; thereby, a regular somatic cell contains two full sets of genomes....
of lambdoid prophage

Prophage

A prophage is a phage genome inserted as part of the linear structure of the DNA chromosome of a bacterium. A temperate phage integrated into the host chromosome or existing as an extrachromosomal plasmid....
s. The toxins are named for Kiyoshi Shiga

Kiyoshi Shiga

was a Japan physician and bacteriology....
, who first described the bacterial origin of dysentery

Dysentery

Dysentery is a disorder of the digestive system that results in severe diarrhea containing mucus and/or blood in the feces. If untreated, Dysentery can be fatal....
caused by Shigella dysenteriae
Shigella dysenteriae

Shigella dysenteriae is a species of the rod-shaped bacterial genus Shigella. Shigella can cause shigellosis . Shigellae are Gram-negative, Endospore, Facultative anaerobic organism, Motility bacteria....
. The most common sources for Shiga toxin are the bacteria S. dysenteriae and the Shigatoxigenic group of Escherichia coli
Escherichia coli

'Escherichia coli' , is a Gram negative bacterium that is commonly found in the lower gastrointestinal tract of warm-blooded animals. Most E....
(STEC), which includes serotype

Serotype

For the term's use in bacteriology, see serovar.Transplants between genetically non-identical humans induce the creation of antibodies in the recipient....
O157:H7

Escherichia coli O157:H7

Escherichia coli O157:H7 is an enterohemorrhagic strain of the Bacteria Escherichia coli and a cause of foodborne illness. Infection often leads to bloody diarrhea, and occasionally to kidney failure, especially in young children and elderly people....
and other enterohemorrhagic E.

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Encyclopedia

Shiga toxins are a family of related toxin
Exotoxin

An exotoxin is a toxin excreted by a microrganism, including bacterium, fungi, algae, and protozoa. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism....
s with two major groups, Stx1 and Stx2, whose genes are considered to be part of the genome
Genome

In classical genetics, the genome of a diploid organism including eukarya refers to a full set of chromosomes or genes in a gamete; thereby, a regular somatic cell contains two full sets of genomes....
of lambdoid prophage
Prophage

A prophage is a phage genome inserted as part of the linear structure of the DNA chromosome of a bacterium. A temperate phage integrated into the host chromosome or existing as an extrachromosomal plasmid....
s. The toxins are named for Kiyoshi Shiga
Kiyoshi Shiga

was a Japan physician and bacteriology....
, who first described the bacterial origin of dysentery
Dysentery

Dysentery is a disorder of the digestive system that results in severe diarrhea containing mucus and/or blood in the feces. If untreated, Dysentery can be fatal....
caused by Shigella dysenteriae
Shigella dysenteriae

Shigella dysenteriae is a species of the rod-shaped bacterial genus Shigella. Shigella can cause shigellosis . Shigellae are Gram-negative, Endospore, Facultative anaerobic organism, Motility bacteria....
. The most common sources for Shiga toxin are the bacteria S. dysenteriae and the Shigatoxigenic group of Escherichia coli
Escherichia coli

'Escherichia coli' , is a Gram negative bacterium that is commonly found in the lower gastrointestinal tract of warm-blooded animals. Most E....
(STEC), which includes serotype
Serotype

For the term's use in bacteriology, see serovar.Transplants between genetically non-identical humans induce the creation of antibodies in the recipient....
O157:H7
Escherichia coli O157:H7

Escherichia coli O157:H7 is an enterohemorrhagic strain of the Bacteria Escherichia coli and a cause of foodborne illness. Infection often leads to bloody diarrhea, and occasionally to kidney failure, especially in young children and elderly people....
and other enterohemorrhagic E. coli.
Nomenclature
There are many terms that microbiologists use to describe Shiga toxin and differentiate between different forms of it. Many of these terms are used interchangeably.
1) Shiga toxin (Stx) - true Shiga toxin is produced by Shigella dysenteriae.
2) Shiga-like toxin 1 and 2 (SLT-1 and 2 or Stx-1 and 2) - the Shiga toxins produced by some E. coli strains. Stx-1 differs from Stx by only 1 amino acid. Stx-2 shares 56% sequence homology with Stx-1.
3) Cytotoxins - an archaic denotation for Stx, used in a broad sense.
4) Verocytotoxins - a seldom used denotation for Stx, from the hypersensitivity of Vero cells
Vero cells

Vero cells are lineages of cell_ used in cell cultures.The Vero lineage was isolated from kidney epithelial cells extracted from an African green monkey ....
to Stx.

Mechanism
Shiga toxins act to inhibit protein synthesis
Protein synthesis

Protein synthesis is the creation of proteins using DNA and RNA. Proteins can often be synthesized directly from genes by Translation mRNA. When a protein is harmful and needs to be available on short notice or in large quantities, a protein precursor is produced....
within target cells by a mechanism similar to that of ricin
Ricin

Ricin is a protein toxin that is solvent extraction from the Castor oil plant .The US Centers for Disease Control gives a possible minimum figure of 500 micrograms for the lethal dose of ricin in humans if exposure is from injection or inhalation....
toxin produced by Ricinus communis. After entering a cell, the protein functions as an N-glycosidase, cleaving several nucleobase
Nucleobase

Nucleobases are the parts of DNA and RNA that may be involved in pairing . The main ones are cytosine, guanine, adenine , thymine and uracil , abbreviated as C, G, A, T, and U, respectively....
s from the RNA
RNA

Ribonucleic acid is a type of molecule that consists of a long chain of nucleotide units. Each nucleotide consists of a nucleobase, a ribose sugar, and a phosphate....
that comprises the ribosome
Ribosome

Ribosomes are complexes of RNA and protein that are found in all cell s. Ribosomes from bacteria, archaea and eukaryotes, the three domains of life on Earth, have significantly different structure and RNA....
, thereby halting protein synthesis.

Structure
The toxin has two subunits—designated A and B—and is one of the AB₅ toxins
AB5 toxin

The AB5 toxins are six-component protein complexes secreted by a number of pathogenicity bacteria. All share a similar structure and mechanism for entering targeted host cells....
. The B subunit is a pentamer
Oligomer

In chemistry, an oligomer consists of a limited number of monomer units , in contrast to a polymer which, at least in principle, consists of an unbounded number of monomers....
that binds to specific glycolipid
Glycolipid

Glycolipids are carbohydrate-attached lipids. Their role is to provide energy and also serve as genetic marker for Cell recognition.They occur where a carbohydrate chain is associated with phospholipids on the exoplasmic surface of the cell biological membrane....
s on the host cell, specifically globotriaosylceramide (Gb3). Following this, the A subunit is internalised and cleaved into two parts. The A1 component then binds to the ribosome, disrupting protein synthesis. Stx-2 has been found to be approximately 400 times more toxic (as quantified by LD50 in mice) than Stx-1.

Gb3 is, for unknown reasons, present in greater amounts in renal epithelial tissues, to which the renal toxicity of Shiga toxin may be attributed.

The toxin requires highly specific receptor
Receptor (biochemistry)

In biochemistry, a receptor is a protein molecule, embedded in either the plasma membrane or cytoplasm of a cell, to which a mobile signaling molecule may attach....
s on the cells' surface in order to attach and enter the cell; species such as cattle
Cattle

Cattle, colloquially referred to as cows, are domestication ungulates, a member of the subfamily Bovinae of the family Bovidae. They are raised as livestock for meat , dairy products , leather and as draft animals ....
, swine, and deer
Deer

Deer are the ruminant mammals forming the family Cervidae . A number of broadly similar animals from related families within the order even-toed ungulate are often also called 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.

See also

Cholera toxin
Cholera toxin

Cholera toxin is a protein complex secreted by the bacterium Vibrio cholerae. CTX is responsible for the harmful effects of cholera infection....
Enterotoxin
Enterotoxin

An enterotoxin is a protein toxin released by a microorganism in the intestine.Enterotoxins are frequently cytotoxic and kill cells by altering the Semipermeable membrane of the epithelial cells of the intestinal wall....
Pertussis toxin
Pertussis toxin

Pertussis toxin is a protein-based AB5 toxin exotoxin produced by the bacterium Bordetella pertussis, which causes whooping cough. PT is involved in the colonization of the respiratory tract and the establishment of infection....

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