Shiga toxin
Encyclopedia
Shiga toxins are a family of related toxin
s with two major groups, Stx1 and Stx2, whose genes are considered to be part of the genome
of lambdoid prophage
s. The toxins are named for Kiyoshi Shiga
, who first described the bacterial origin of dysentery
caused by Shigella dysenteriae
. The most common sources for Shiga toxin are the bacteria S. dysenteriae and the Shigatoxigenic group of Escherichia coli
(STEC), which includes serotypes
O157:H7
, O104:H4
, and other enterohemorrhagic
E. coli (EHEC).
toxin produced by Ricinus communis. After entering a cell, the protein functions as an N-glycosidase, cleaving a specific adenine nucleobase
from the 28S RNA
of the 60S subunit of the ribosome, thereby halting protein synthesis.
. The B subunit is a pentamer
that binds to specific glycolipid
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. Gb3 is also found in CNS 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.
The toxin requires highly specific receptor
s 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.
Exotoxin
An exotoxin is a toxin excreted by a microorganism, like bacteria, fungi, algae, and protozoa. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host...
s with two major groups, Stx1 and Stx2, whose genes are considered to be part of the genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
of lambdoid prophage
Prophage
A prophage is a phage genome inserted and integrated into the circular bacterial DNA chromosome. A prophage, also known as a temperate phage, is any virus in the lysogenic cycle; it is integrated into the host chromosome or exists as an extrachromosomal plasmid. Technically, a virus may be called...
s. The toxins are named for Kiyoshi Shiga
Kiyoshi Shiga
was a Japanese physician and bacteriologist.-Biography:Shiga was born in Sendai, Miyagi Prefecture, though his original family name was Satō. He graduated from the Medical School of Tokyo Imperial University in 1896 and went to work at the Institute for the Study of Infectious Diseases under Dr....
, who first described the bacterial origin of dysentery
Dysentery
Dysentery is an inflammatory disorder of the intestine, especially of the colon, that results in severe diarrhea containing mucus and/or blood in the faeces with fever and abdominal pain. If left untreated, dysentery can be fatal.There are differences between dysentery and normal bloody diarrhoea...
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, non-spore-forming, facultatively anaerobic, non-motile bacteria.S...
. 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, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
(STEC), which includes serotypes
Serotype
Serotype or serovar refers to distinct variations within a subspecies of bacteria or viruses. These microorganisms, viruses, or cells are classified together based on their cell surface antigens...
O157:H7
Escherichia coli O157:H7
Escherichia coli O157:H7 is an enterohemorrhagic strain of the bacterium Escherichia coli and a cause of foodborne illness. Infection often leads to hemorrhagic diarrhea, and occasionally to kidney failure, especially in young children and elderly persons...
, O104:H4
Escherichia coli O104:H4
Escherichia coli O104:H4 is a rare enterohemorrhagic strain of the bacterium Escherichia coli, and the cause of the 2011 Escherichia coli O104:H4 outbreak...
, and other enterohemorrhagic
Enterohemorrhagic
Enterohemorrhagic microorganisms are those that, as part of their pathogenesis, cause bloody diarrhea and colitis. While many pathogens are enterohemorrhagic, most cases observed are derived of E. coli serotype O157:H7. The E. coli O104:H4 strain identified as the cause of the 2011 outbreak in...
E. coli (EHEC).
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.- Shiga toxin (Stx) - true Shiga toxin is produced by Shigella dysenteriaeShigella dysenteriaeShigella dysenteriae is a species of the rod-shaped bacterial genus Shigella. Shigella can cause shigellosis . Shigellae are Gram-negative, non-spore-forming, facultatively anaerobic, non-motile bacteria.S...
. - Shiga-like toxinShiga-like toxinShiga-like toxin, also known as verotoxin, is a toxin generated by some strains of Escherichia coli . It is named for its similarity to the AB5-type Shiga toxin produced by the bacteria Shigella dysenteriae....
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. - Cytotoxins - an archaic denotation for Stx, used in a broad sense.
- Verocytotoxins/verotoxins - a seldom used term for Stx, from the hypersensitivity of Vero cellsVero cellsVero cells are lineages of cells 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 within target cells by a mechanism similar to that of ricinRicin
Ricin , from the castor oil plant Ricinus communis, is a highly toxic, naturally occurring protein. A dose as small as a few grains of salt can kill an adult. The LD50 of ricin is around 22 micrograms per kilogram Ricin , from the castor oil plant Ricinus communis, is a highly toxic, naturally...
toxin produced by Ricinus communis. After entering a cell, the protein functions as an N-glycosidase, cleaving a specific adenine nucleobase
Nucleobase
Nucleobases are a group of nitrogen-based molecules that are required to form nucleotides, the basic building blocks of DNA and RNA. Nucleobases provide the molecular structure necessary for the hydrogen bonding of complementary DNA and RNA strands, and are key components in the formation of stable...
from the 28S RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
of the 60S subunit of the ribosome, thereby halting protein synthesis.
Structure
The toxin has two subunits—designated A and B—and is one of the AB5 toxinsAB5 toxin
The AB5 toxins are six-component protein complexes secreted by a number of pathogenic bacteria. All share a similar structure and mechanism for entering targeted host cells.- Structure and mechanism :...
. The B subunit is a pentamer
Oligomer
In chemistry, an oligomer is a molecule that consists of a few monomer units , in contrast to a polymer that, at least in principle, consists of an unlimited number of monomers. Dimers, trimers, and tetramers are oligomers. Many oils are oligomeric, such as liquid paraffin...
that binds to specific glycolipid
Glycolipid
Glycolipids are lipids with a carbohydrate attached. Their role is to provide energy and also serve as markers for cellular recognition.-Metabolism:...
s on the host cell, specifically globotriaosylceramide
Globotriaosylceramide
Globotriaosylceramide is a ganglioside.It is also known as "CD77". It is one of the few clusters of differentiation that is not a protein.It is also known as "ceramide trihexoside".It is formed by A4GALT.It is metabolized by Alpha-galactosidase....
(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. Gb3 is also found in CNS 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.
The toxin requires highly specific receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
s on the cells' surface in order to attach and enter the cell; species such as cattle
Cattle
Cattle are the most common type of large domesticated ungulates. They are a prominent modern member of the subfamily Bovinae, are the most widespread species of the genus Bos, and are most commonly classified collectively as Bos primigenius...
, swine, and deer
Deer
Deer are the ruminant mammals forming the family Cervidae. Species in the Cervidae family include white-tailed deer, elk, moose, red deer, reindeer, fallow deer, roe deer and chital. Male deer of all species and female reindeer grow and shed new antlers each year...
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 toxinCholera toxinCholera toxin is a protein complex secreted by the bacterium Vibrio cholerae. CTX is responsible for the massive, watery diarrhea characteristic of cholera infection.- Structure :...
- EnterotoxinEnterotoxinAn enterotoxin is a protein toxin released by a microorganism in the intestine. Enterotoxins are chromosomally encoded exotoxins that are produced and secreted from several bacterial organisms. They are often heat-stable, and are of low molecular weight and water-soluble...
- Pertussis toxinPertussis toxinPertussis toxin is a protein-based AB5-type 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...
- 2011 German E. coli outbreak