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a poisonous substance produced during the metabolism and growth of certain microorganisms and some higher plant and animal species

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(特にバクテリアの)毒素

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/05/14 01:50:39」(JST)

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Ribbon diagram of Shiga toxin (Stx) from S. dysenteriae. From PDB: 1R4Q.

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 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).^[2]^[3]

Nomenclature

Microbiologists use many terms to describe Shiga toxin and differentiate more than one unique form. Many of these terms are used interchangeably.

Shiga toxin (Stx) - true Shiga toxin - is produced by Shigella dysenteriae.
Shiga-like toxins 1 and 2 (SLT-1 and 2 or Stx-1 and 2) are the Shiga toxins produced by some E. coli strains. Stx-1 differs from Stx by only one amino acid. Stx-2 shares 56% sequence identity with Stx-1.
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 Vero cells to Stx.

Mechanism

Shiga toxins act to inhibit protein synthesis within target cells by a mechanism similar to that of ricin.^[4] After entering a cell via a macropinosome,^[5] the protein cleaves a specific adenine nucleobase from the 28S RNA of the 60S subunit of the ribosome, thereby halting protein synthesis.^[6]

Structure

The toxin has two subunits—designated A (mol. wt. 32000 D) and B (mol. wt. 7700 D)—and is one of the AB₅ toxins. The B subunit is a pentamer that binds to specific glycolipids 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 about 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 central nervous system neurons and endothelium, which may lead to neurotoxicity.^[7] Stx-2 is also known to increase the expression of its receptor GB3 and cause neuronal dysfunctions.^[8]

The toxin requires highly specific receptors on the cells' surface 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.^[9]

References

^ Friedman D, Court D (2001). "Bacteriophage lambda: alive and well and still doing its thing". Current Opinion in Microbiology 4 (2): 201–7. doi:10.1016/S1369-5274(00)00189-2. PMID 11282477.
^ Beutin L (2006). "Emerging enterohaemorrhagic Escherichia coli, causes and effects of the rise of a human pathogen". J Vet Med B Infect Dis Vet Public Health 53 (7): 299–305. doi:10.1111/j.1439-0450.2006.00968.x. PMID 16930272.
^ Spears; et al. (2006). "A comparison of Enteropathogenic and enterohaemorragic E.coli pathogenesis". FEMS Microbiology Letters 255: 187–202. doi:10.1111/j.1574-6968.2006.00119.x.
^ Sandvig K, van Deurs B (2000). "Entry of ricin and Shiga toxin into cells: molecular mechanisms and medical perspectives". The EMBO Journal 19 (22): 5943–50. doi:10.1093/emboj/19.22.5943. PMC 305844. PMID 11080141.
^ Lukyanenko, V.; Malyukova, I.; Hubbard, A.; Delannoy, M.; Boedeker, E.; Zhu, C.; Cebotaru, L.; Kovbasnjuk, O. (2011). "Enterohemorrhagic Escherichia coli infection stimulates Shiga toxin 1 macropinocytosis and transcytosis across intestinal epithelial cells". AJP: Cell Physiology 301 (5): C1140–C1149. doi:10.1152/ajpcell.00036.2011. PMC 3213915. PMID 21832249.
^ Sandvig K, Bergan J, Dyve A, Skotland T, Torgersen M.L. (2010). "Endocytosis and retrograde transport of Shiga toxin". Toxicon. 56 Suppl 7: 1181–1185. doi:10.1016/j.toxicon.2009.11.021. PMID 2047652.
^ Obata F, Tohyama K, Bonev AD, Kolling GL, Keepers TR, Gross LK, Nelson MT, Sato S, Obrig TG (2008). "Shiga Toxin 2 Affects the Central Nervous System through Receptor Globotriaosylceramide Localized to Neurons". J Infect Dis 198 (9): 1398–1406. doi:10.1086/591911. PMC 2684825. PMID 18754742.
^ Tironi-Farinati C, Loidl CF, Boccoli J, Parma Y, Fernandez-Miyakawa ME, Goldstein J. (2010). "Intracerebroventricular Shiga toxin 2 increases the expression of its receptor globotriaosylceramide and causes dendritic abnormalities". J Neuroimmunol 222 (1–2): 48–61. doi:10.1016/j.jneuroim.2010.03.001. PMID 20347160.
^ Asakura H, Makino S, Kobori H, Watarai M, Shirahata T, Ikeda T, Takeshi K (2001). "Phylogenetic diversity and similarity of active sites of Shiga toxin (stx) in Shiga toxin-producing Escherichia coli (STEC) isolates from humans and animals". Epidemiol Infect 127 (1): 27–36. doi:10.1017/S0950268801005635. PMC 2869726. PMID 11561972.

External links

Shiga toxin at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 小児における志賀毒素産生性大腸菌（STEC）溶血性尿毒症症候群（HUS）の臨床症状および診断 clinical manifestations and diagnosis of shiga toxin producing escherichia coli stec hemolytic uremic syndrome hus in children
2. 小児における志賀毒素産生性大腸菌（STEC）溶血性尿毒症症候群（HUS）の治療および予後 treatment and prognosis of shiga toxin producing escherichia coli stec hemolytic uremic syndrome hus in children
3. 腸管出血性大腸菌（EHEC）感染症の臨床症状、診断および治療 clinical manifestations diagnosis and treatment of enterohemorrhagic escherichia coli ehec infection
4. 腸管出血性大腸菌（EHEC）の微生物学、病因、疫学、および予防 microbiology pathogenesis epidemiology and prevention of enterohemorrhagic escherichia coli ehec
5. 赤痢菌感染：臨床症状および診断 shigella infection clinical manifestations and diagnosis

English Journal

Persistence of Escherichia coli O157 and non-O157 strains in agricultural soils.

Ma J1, Mark Ibekwe A2, Crowley DE3, Yang CH4.
The Science of the total environment.Sci Total Environ.2014 Aug 15;490:822-9. doi: 10.1016/j.scitotenv.2014.05.069. Epub 2014 Jun 5.
Shiga toxin producing Escherichia coli O157 and non-O157 serogroups are known to cause serious diseases in human. However, research on the persistence of E. coli non-O157 serogroups in preharvest environment is limited. In the current study, we compared the survival behavior of E. coli O157 to that
PMID 24907617

Detection and source tracking of Escherichia coli, harboring intimin and Shiga toxin genes, isolated from the Little Bighorn River, Montana.

Hamner S1, Broadaway SC, Berg E, Stettner S, Pyle BH, Big Man N, Old Elk J, Eggers MJ, Doyle J, Kindness L, Good Luck B, Ford TE, Camper AC.
International journal of environmental health research.Int J Environ Health Res.2014 Aug;24(4):341-62. doi: 10.1080/09603123.2013.835030. Epub 2013 Sep 17.
The Little Bighorn River flows through the Crow Indian Reservation in Montana. In 2008, Escherichia coli concentrations as high as 7179 MPN/100 ml were detected in the river at the Crow Agency Water Treatment Plant intake site. During 2008, 2009, and 2012, 10 different serotypes of E. coli, includ
PMID 24044742

Detection of Shiga toxin (Stx)-producing Escherichia coli (STEC) in bovine dairy herds in Northern Italy.

Trevisani M1, Mancusi R2, Delle Donne G2, Bacci C3, Bassi L3, Bonardi S3.
International journal of food microbiology.Int J Food Microbiol.2014 Aug 1;184C:45-49. doi: 10.1016/j.ijfoodmicro.2013.12.033. Epub 2014 Jan 10.
The aim of this study was to monitor the presence of Shiga toxin (Stx)-producing Escherichia coli in dairy farms authorized to sell raw milk and other farms, located in the same area, which sell milk to industry or use it to produce Parmesan or Grana cheese. Our research was focused on the serogroup
PMID 24495690

Japanese Journal

Highlighted Paper selected by Editor-in-Chief : Stable Expression and Characterization of Monomeric and Dimeric Recombinant Hybrid-IgG/IgA Immunoglobulins Specific for Shiga Toxin