- Shiga-like toxin
Shiga-like toxin is a AB5-type
Shiga toxinproduced by the bacteria" Escherichia coli" and also known as verotoxin. In 1977, researchers in Ottawa, Ontariorediscovered the Shiga toxin produced by " Shigella dysenteriae" in "E. coli". [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] The "E. coli" version was named "verotoxin" because of the ability of the toxic protein to kill "Vero" cells (African green monkey kidneycells) 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 receptors on the cells' surface in order to attach and enter the cell;
speciessuch as cattle, swine, and deerwhich 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
electrolytelevels, 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
toxicityof 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.
tructure and Mechanism
tructure of the Toxin
The toxin has a molecular weight of 68,000
da. It is a multi-subunit proteinmade 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 membraneknown as Gb3 and the complex enters the 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 RNAcomponent of the ribosome to inactivate it and so bring a halt to protein synthesisleading 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 foodor 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 arteriesor 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 poisoningwith Shiga toxin often also has effects on the lungs and the nervous system.
ource of toxin gene
It has been suggested by some researchers that the gene coding for Shigella-like toxin comes from a toxin-convertinglambdoid
prophage, such as H-19B or 933W, inserted into the bacteria's chromosomevia transduction. [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]
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