Shiga toxin
Shiga-like toxin beta subunit | |||||||||
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Identifiers | |||||||||
Symbol | SLT_beta | ||||||||
TCDB | 1.C.54 | ||||||||
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Shiga-like toxin subunit A | |
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Identifiers | |
Symbol | Shiga-like_toxin_subunit_A |
SCOP2 | 1r4q / SCOPe / SUPFAM |
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.[1] The toxins are named after Kiyoshi Shiga, who first described the bacterial origin of dysentery caused by Shigella dysenteriae.[2] Shiga-like toxin (SLT) is a historical term for similar or identical toxins produced by Escherichia coli.[3] 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.[4][5]
Nomenclature
- Shiga toxin type 1 and type 2 (Stx-1 and 2) are the Shiga toxins produced by some E. coli strains. Stx-1 is identical to Stx of Shigella spp. or differs by only one amino acid.sequence identity with Stx-1.[citation needed]
- Cytotoxins – an archaic denotation for Stx – is used in a broad sense.
- Verocytotoxins/verotoxins – a seldom-used term for Stx – is from the hypersensitivity of
- The term Shiga-like toxins is another antiquated term which arose prior to the understanding that Shiga and Shiga-like toxins were identical.[10]
History
The toxin is named after Kiyoshi Shiga, who discovered S. dysenteriae in 1897.[2] In 1977, researchers in Ottawa, Ontario discovered the Shiga toxin normally produced by Shigella dysenteriae in a line of E. coli.[11] 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
Transmission
The toxin requires highly specific
Clinical significance
Symptoms of Shiga toxin ingestion include abdominal pain as well as watery diarrhea. Severe life-threatening cases are characterized by hemorrhagic colitis (HC).[15]
The toxin is associated with
The toxin is effective against small blood vessels, such as found in the
Structure and mechanism
Mechanism
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.[16] The Shiga toxin (a non-pore forming toxin) is transferred to the cytosol via Golgi network and endoplasmic reticulum (ER). From the Golgi toxin is trafficked to the ER. Shiga toxins act to inhibit
The bacterial Shiga toxin can be used for targeted therapy of gastric cancer, because this tumor entity expresses the receptor of the Shiga toxin. For this purpose an unspecific chemotherapeutical is conjugated to the B-subunit to make it specific. In this way only the tumor cells, but not healthy cells, are destroyed during therapy.[21]
Structure
The toxin has two subunits—designated A (
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 central nervous system neurons and endothelium, which may lead to neurotoxicity.[24] Stx-2 is also known to increase the expression of its receptor GB3 and cause neuronal dysfunctions.[25]
See also
- 2011 German E. coli outbreak
- Cholera toxin
- Enterotoxin
- Pertussis toxin
References
- PMID 11282477.
- ^ PMID 10524979.
- PMID 12123543.
- PMID 16930272.
- PMID 16448495.
- PMID 25590020.
- PMID 8408571.
- PMID 8039905.
- PMID 2199511.
- PMID 22760050.
- PMID 338490.
- PMID 10382973.
- ISBN 978-3319505800.
- PMID 11561972.
- PMID 17557838.
- S2CID 4410673.
- PMID 11080141.
- S2CID 220255474.
- PMID 21832249.
- PMID 2047652.
- ^ Gastric adenocarcinomas express the glycosphingolipid Gb3/CD77: Targeting of gastric cancer cells with Shiga toxin B-subunit
- S2CID 4274763.
- S2CID 3343088.
- PMID 18754742.
- S2CID 11910897.
External links
- UniprotKB entries: stxA1 Q9FBI2, stxB1 Q7BQ98, stxA2 P09385, stxB2 P09386
- Shiga+toxin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Shiga-Like+Toxin+I at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Shiga-Like+Toxin+II at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- "Shigella" in Todar's Online Textbook of Bacteriology
- "The So-called Chromosomal Verotoxin Genes are Actually Carried by Defective Prophages" ()