関: shiga toxin、verocytotoxin

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/23 00:04:33」(JST)

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Shiga-like toxin, also known as verotoxin,^[1]^[2] is a toxin generated by some strains of Escherichia coli (but see below).^[3] It is named for its similarity to the AB5-type Shiga toxin produced by the bacteria Shigella dysenteriae, [ see Vero cell ].

There are two types, known as SLT1 and SLT2.^[4]

History

Transmission

As with Shiga toxin, 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.

Clinical significance

The Shiga-like toxin is associated with Hemolytic-uremic syndrome.

Structure and mechanism

SLT2 from Escherichia coli O157:H7. The A subunit is shown in red (top), and the B subunits, forming a pentamer, in different shades of blue (bottom). From PDB: 1R4P .

Structure

The toxin is a multisubunit protein made up one molecule of 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 glycolipid globotriaosylceramide (Gb3).^[5] 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.^[6] 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 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 Shiga-like toxin comes from a toxin-converting lambdoid prophage, such as H-19B or 933W, inserted into the bacteria's chromosome via transduction.^[7]

References

^[8]

^ Beutin L, Geier D, Steinrück H, Zimmermann S, Scheutz F (September 1993). "Prevalence and some properties of verotoxin (Shiga-like toxin)-producing Escherichia coli in seven different species of healthy domestic animals". Journal of clinical microbiology 31 (9): 2483–8. PMC 265781. PMID 8408571.
^ Bitzan M, Richardson S, Huang C, Boyd B, Petric M, Karmali MA (August 1994). "Evidence that verotoxins (Shiga-like toxins) from Escherichia coli bind to P blood group antigens of human erythrocytes in vitro". Infection and immunity 62 (8): 3337–47. PMC 302964. PMID 8039905.
^ Giraldi R, Guth BE, Trabulsi LR (June 1990). "Production of Shiga-like toxin among Escherichia coli strains and other bacteria isolated from diarrhea in São Paulo, Brazil". Journal of clinical microbiology 28 (6): 1460–2. PMC 267957. PMID 2199511.
^ Zhu Q, Li L, Guo Z, Yang R (June 2002). "Identification of Shiga-like toxin Escherichia coli isolated from children with diarrhea by polymerase chain reaction". Chin. Med. J. 115 (6): 815–8. PMID 12123543.
^ Kaper, JB; Nataro, JP; Mobley, HL (Feb 2004). "Pathogenic Escherichia coli.". Nature reviews. Microbiology 2 (2): 123–40 [129]. doi:10.1038/nrmicro818. PMID 15040260. |accessdate= requires |url= (help)
^ Römer W, Berland L, Chambon V et al. (November 2007). "Shiga toxin induces tubular membrane invaginations for its uptake into cells". Nature 450 (7170): 670–5. doi:10.1038/nature05996. PMID 18046403.
^ Satoshi MIZUTANI, Naoki NAKAZONO, and Yoshinobu SUGINO (1999). "The So-called Chromosomal Verotoxin Genes are Actually Carried by Defective Prophages". Dna Research 6 (2): 141–143. doi:10.1093/dnares/6.2.141. PMID 10382973.
^ Stein PE, Boodhoo A, Tyrrell GJ, Brunton JL, Read RJ (February 1992). "Crystal structure of the cell-binding B oligomer of verotoxin-1 from E. coli". Nature 355 (6362): 748–50. doi:10.1038/355748a0. PMID 1741063.

External links

Shiga-Like Toxin I at the US National Library of Medicine Medical Subject Headings (MeSH)
Shiga-Like Toxin II at the US National Library of Medicine Medical Subject Headings (MeSH)
http://www.textbookofbacteriology.net/Shigella.html
http://www.textbookofbacteriology.net/Shigella.html
http://dnaresearch.oxfordjournals.org/cgi/reprint/6/2/141?ck=nck

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. 赤痢菌感染：臨床症状および診断 shigella infection clinical manifestations and diagnosis
5. 小児における溶血性尿毒症症候群の概要 overview of hemolytic uremic syndrome in children

English Journal

Subtilase contributes to the cytotoxicity of a Shiga toxin-producing Escherichia coli strain encoding three different toxins.

Hauser E1, Bruederle M1, Reich C1, Bruckbauer A1, Funk J1, Schmidt H2.
International journal of food microbiology.Int J Food Microbiol.2016 Jan 18;217:156-61. doi: 10.1016/j.ijfoodmicro.2015.10.023. Epub 2015 Oct 25.
Food-borne Shiga toxin-producing Escherichia coli (STEC) O113:H21 strain TS18/08, that has previously been isolated from mixed minced meat, harbors the Shiga toxin (Stx) encoding allele stx2a, the plasmid-located subtilase cytotoxin encoding allele subAB1 and the cytolethal distending toxin type V e
PMID 26523884

Localizing Carbohydrate Binding Sites in Proteins Using Hydrogen/Deuterium Exchange Mass Spectrometry.

Zhang J1,2, Kitova EN1,2, Li J1,2, Eugenio L3,2, Ng K3,2, Klassen JS4,5.
Journal of the American Society for Mass Spectrometry.J Am Soc Mass Spectrom.2016 Jan;27(1):83-90. doi: 10.1007/s13361-015-1263-2. Epub 2015 Sep 30.
The application of hydrogen/deuterium exchange mass spectrometry (HDX-MS) to localize ligand binding sites in carbohydrate-binding proteins is described. Proteins from three bacterial toxins, the B subunit homopentamers of Cholera toxin and Shiga toxin type 1 and a fragment of Clostridium difficile
PMID 26423923

The Antibiotic Polymyxin B Impairs the Interactions between Shiga Toxins and Human Neutrophils.

Carnicelli D1, Arfilli V1, Ricci F2, Velati C2, Tazzari PL2, Brigotti M3.
Journal of immunology (Baltimore, Md. : 1950).J Immunol.2015 Dec 22. pii: 1500671. [Epub ahead of print]
Hemolytic uremic syndrome (HUS) is the life-threatenig sequela of intestinal infections by Shiga toxin (Stx)-producing Escherichia coli (STEC) in children. Human neutrophils specifically bind Stx through TLR4, the receptor of LPS. The binding could be considered protective (Stx sequestration) or har
PMID 26695372

Japanese Journal

Virulence characteristics of Shiga toxin-producing Escherichia coli from raw meats and clinical samples

Microbiology and immunology 59(3), 114-122, 2015-03
NAID 40020416268

東京都内に流通する牛内臓肉からの糞便系大腸菌群，ベロ毒素産生性大腸菌，Campylobacter jejuni/coli, SalmonellaおよびListeria monocytogenes検出状況

日本食品微生物学会雑誌 32(4), 209-214, 2015
NAID 130005118640

百日咳罹患後発症した非定型溶血性尿毒症症候群の一例

日本集中治療医学会雑誌 22(5), 430-434, 2015
NAID 130005098015

Related Pictures

★リンクテーブル★

リンク元	「ベロ毒素」「shiga toxin」「verocytotoxin」
拡張検索	「verotoxin-producing E. coli」

「ベロ毒素」

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Shiga-like toxin beta subunit
Identifiers
Symbol	SLT_beta
Pfam	PF02258
InterPro	IPR003189
SCOP	2bos
SUPERFAMILY	2bos
TCDB	1.C.54
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary