Shigella toxin

Shiga toxins are a family of related toxins with two major groups, Stx1 and Stx2, expressed by genes considered to be part of the genome of lambdoid prophages. The toxins are named after Kiyoshi Shiga, who first described the bacterial origin of dysentery caused by Shigella dysenteriae. Shiga-like toxin (SLT) is a historical term for similar or identical toxins produced by Escherichia coli. The most common sources for Shiga toxin are the bacteria S. dysenteriae and some serotypes of Escherichia coli (STEC), which includes serotypes O157:H7, and O104:H4. Shiga toxins are a family of related toxins with two major groups, Stx1 and Stx2, expressed by genes considered to be part of the genome of lambdoid prophages. The toxins are named after Kiyoshi Shiga, who first described the bacterial origin of dysentery caused by Shigella dysenteriae. Shiga-like toxin (SLT) is a historical term for similar or identical toxins produced by Escherichia coli. The most common sources for Shiga toxin are the bacteria S. dysenteriae and some serotypes of Escherichia coli (STEC), which includes serotypes O157:H7, and O104:H4. Microbiologists use many terms to describe Shiga toxin and differentiate more than one unique form. Many of these terms are used interchangeably. The toxin is named after Kiyoshi Shiga, who discovered S. dysenteriae in 1897. 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 microbiology advances, the historical variation in nomenclature (which arose because of gradually advancing science in multiple places) is increasingly giving way to recognizing all of these molecules as 'versions of the same toxin' rather than 'different toxins.':2–3 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. Symptoms of Shiga toxin ingestion include abdominal pain as well as watery diarrhea. Severe life-threatening cases are characterized by hemorrhagic colitis (HC). The toxin is associated with hemolytic-uremic syndrome. 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. 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.The shiga toxin (a non-pore forming toxin) is transferred to the cytosol via Golgi network and ER. From the Golgi toxin is trafficked to the ER.Shiga toxins act to inhibit protein synthesis within target cells by a mechanism similar to that of ricin. After entering a cell via a macropinosome, the protein (A subunit) cleaves a specific adenine nucleobase from the 28S RNA of the 60S subunit of the ribosome, thereby halting protein synthesis. As they mainly act on the lining of the blood vessels, the vascular endothelium, a breakdown of the lining and hemorrhage eventually occurs. The first response is commonly a bloody diarrhea. This is because Shiga toxin is usually taken in with contaminated food or water.