Shiga toxin

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PDB 1r4q.png|thumb|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 O104:H4, and other enterohemorrhagic E. coli (EHEC).[2][3]

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]


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]

See also


  1. Friedman D, Court D (2001). "Bacteriophage lambda: alive and well and still doing its thing". Current Opinion in Microbiology. 4 (2): 201–7. PMID 11282477. doi:10.1016/S1369-5274(00)00189-2. 
  2. 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. PMID 16930272. doi:10.1111/j.1439-0450.2006.00968.x. 
  3. Spears; et al. (2006). "A comparison of Enteropathogenic and enterohaemorragic E.coli pathogenesis". FEMS Microbiology Letters: 187–202. 
  4. 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. PMC 305844Freely accessible. PMID 11080141. doi:10.1093/emboj/19.22.5943. 
  5. 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. PMC 3213915Freely accessible. PMID 21832249. doi:10.1152/ajpcell.00036.2011. 
  6. 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. PMID 2047652. doi:10.1016/j.toxicon.2009.11.021. 
  7. 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. PMC 2684825Freely accessible. PMID 18754742. doi:10.1086/591911. 
  8. 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. PMID 20347160. doi:10.1016/j.jneuroim.2010.03.001. 
  9. 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. PMC 2869726Freely accessible. PMID 11561972. doi:10.1017/S0950268801005635. 

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