Shiga toxin: Difference between revisions
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==Introduction== | ==Introduction== | ||
'''Shiga Toxins''' are a family of [http://en.wikipedia.org/wiki/AB5_toxin AB5] toxins (Stx1 and Stx2) which cause dysentery | '''Shiga Toxins''' are a family of [http://en.wikipedia.org/wiki/AB5_toxin AB5] toxins (Stx1 and Stx2) which cause dysentery, hemolytic-uremic syndrome, and potentially renal failure in humans. They are primarily secreted by Shiga toxin-encoding Escherichia coli (STEC), notably by the 0157:H7 strain<ref name=Wagner>PMID: 12010491</ref> and shigella dysentarie. STECs are one of the major foodborne pathogens, affecting both developed and third-world countries. The stx gene is not endogenous to these strains, but is introduced through horizontal gene transfer from environmental prophages of the lambdoid bacteriophage family and incorporated into the E. Coli genome.<ref name=Wagner>PMID: 12010491</ref> Shiga Toxins are closely related to [[ricin]], which is structurally and mechanistically similar. Shiga toxin acts to inhibit protein synthesis in eukaryotic cells and is the main virulence factor of STEC. | ||
==Structure== | ==Structure== | ||
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==Function== | ==Function== | ||
Shiga Toxin acts as an N-glycosidase, removing an adenine from the 60S ribosomal rRNA of a target cell leading to reduced protein synthesis.<ref name=Di>PMID: 21184769</ref> The B subunit is necessary for binding to globo series glycolipid globotriaosylceramide (Gb3), a eukaryotic membrane receptor, where it is then endocytosed and proteolytically cleaved into two active A subunits and a B subunit.<ref name=Lenz>PMID: 2170899</ref> Once the A subunit is transported to the cytosol it acts by depurinating the 32S ribosomal RNA which leads to inhibition of protein elongation and ultimately cellular apoptosis. On the A subunit <scene name='Shiga_toxin/Active_site/1'>Tyr77, Tyr114, Glu167, Arg170, and Trp203</scene> are all essential in glycosidic activity.<ref name=Di>PMID: 21184769</ref> | |||
==Human Interaction== | |||
0157:H7 STECs are spread to humans through a fecal-oral mechanism, primarily from ingestion of food contaminated with fecal material. Cattle, goats, and sheep are the primary reservoir of STECs and their close proximity to food sources as well as the use of animal feces for fertilizer makes them the main route of contamination.<ref name=Herold>PMID: 15493821</ref> Inadequate sanitation and contamination of meat during slaughter can both lead to STEC contaminated food at the market. Once ingested the STEC can survive the high acid environment of the stomach and progress to the gut where they attach firmly to gut mucosa via the [http://en.wikipedia.org/wiki/Intimin intimin adhesin protein]. | |||
Treatment with antibiotics is contraindicated as antibiotic treatment has been demonstrated to increase Stx production up to one hundred fold.<ref name=Herold>PMID: 15493821</ref> This results from the link between Stx production (and phage induction) to the [http://en.wikipedia.org/wiki/SOS_response SOS response pathway].<ref name=Herold>PMID: 15493821</ref> | |||
==3D structures== | ==3D structures== | ||