Shiga-like toxin
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2008-07-01T14:26:24Z
Dnestr
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/* Source of toxin gene */
'''Shiga-like toxin''' is a [[AB5 toxin|AB5-type]] [[Shiga toxin]] produced by the [[bacteria]] ''[[Escherichia coli]]'' and also known as '''verotoxin'''. In 1977, researchers in [[Ottawa]], [[Ontario]] rediscovered the Shiga toxin produced by ''[[Shigella dysenteriae]]'' in ''E. coli''.<ref>{{cite journal |author=Konowalchuk J, Speirs J, Stavric S |title=Vero response to a cytotoxin of Escherichia coli |journal=Infect. Immun. |volume=18 |issue=3 |pages=775–9 |year=1977 |pmid=338490}}</ref> The ''E. coli'' version was named "verotoxin" because of the ability of the toxic protein to kill [[Vero cell|''Vero'' cells]] ([[Chlorocebus|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.
As with Shiga toxin, the toxin requires highly specific [[Receptor (biochemistry)|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.
The syndromes associated with shiga toxin include [[dysentery]], hemorrhagic colitis, and [[hemolytic uremic syndrome]]. The name is dependent upon the causative organism and the symptoms, which may include severe diarrhea, abdominal pain, vomiting, and bloody urine (in the case of [[hemolytic uremic syndrome]]).
The onset of symptoms is generally within a few hours, with higher doses leading to more rapid onset. There is no antidote for the toxin. Supportive care requires maintenance of fluid and [[electrolyte]] levels, and monitoring and support of kidney function.
Immunoassays are available for rapid diagnosis of the toxin.
Inactivation of the toxin is achieved by steam treatment, oxidizing agents such as bleach, and chemical sterilizing agents such as [[glutaraldehyde]].
The [[toxicity]] of Shiga Toxin for the mouse (LD50) is <20 micrograms/kg by intravenous or intraperitoneal administration. There is no published data on the inhalation toxicity of Shiga toxin. However, there are often indirect effects on the lungs when the toxin is taken in as a food contaminant.
==Structure and Mechanism==
===Structure of the Toxin===
The toxin has a molecular weight of 68,000 [[da]]. It is a multi-subunit [[protein]] made up one molecule of an 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 Gb3 and the complex enters the cell. When the protein is inside the cell, the A subunit interacts with the [[ribosome|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. 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]].
==Source of toxin gene==
It has been suggested by some researchers that the gene coding for Shigella-like toxin comes from a toxin-converting
lambdoid [[prophage]], such as H-19B or 933W, inserted into the [[bacteria|bacteria's]] [[chromosome]] via [[transduction_(genetics)|transduction]].<ref>{{cite journal |author=Satoshi MIZUTANI, Naoki NAKAZONO, and Yoshinobu SUGINO |title=The So-called Chromosomal Verotoxin Genes are Actually Carried by Defective Prophages |journal=Dna Research |volume=6 |issue=2 |pages=141–143 |year=1999 |doi=10.1093/dnares/6.2.141}}</ref>
== See also ==
* [[Escherichia coli O157:H7]]
* [[Hemolytic-uremic syndrome]]
== References ==
<references/>
* http://www.textbookofbacteriology.net/Shigella.html
* http://dnaresearch.oxfordjournals.org/cgi/reprint/6/2/141?ck=nck
==External links==
* {{MeshName|Shiga-Like+Toxin+I}}
* {{MeshName|Shiga-Like+Toxin+II}}
* http://www.textbookofbacteriology.net/Shigella.html
[[Category:AB5 toxins]]
[[ja:ベロ毒素]]
[[de:Vero-toxin]]