Shiga toxin is a group of related toxins produced by Shigella dysenteriae and enterohemorrhagic Escherichia coli (EHEC). In the past, shiga toxins have been differentiated as Shiga, Shiga-like or vero toxins but since the toxins produced by the two types of bacteria are very similar, distinctions are no longer made.
- How is Shiga Toxin produced? Shiga toxin is produced by specific strains of Escherichia coli in two isoforms, Shiga 1(Stx1) and Shiga 2(Stx2) which share ~60% sequence homology. These Shiga toxins have the same molecular structures, enzymatic activities, receptor specificity and intracellular trafficking process.
- What are Shiga Toxins composed of? Shiga toxins are composed of two subunits, an enzymatically active A subunit which is non-covalently attached to the pentameric B subunit, responsible for binding to the target cells. The sugar domain of the glycosphingolipid, globotriaosylceramide, Gb3, located on cell surfaces, is specifically bound by the B-subunit. The shiga toxin is internalized by endocytosis and is transported via a retrograde pathway in the Golgi apparatus to the endoplasmic reticulum. The enzymatic A subunit is then translocated to the cytosol where its N-glycosidase activity irreversibly modifies ribosomal 28S RNA leading to inhibition of protein synthesis and causing cell death.
- What is a use for Shiga Toxin? Since the Gb3 receptor is highly expressed in many types of cancers as compared to normal human tissues, the potential use of Shiga toxin to induce apoptosis in cancer cells is currently an active area of research.
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