Shiga toxin

Shiga toxins are a family of related toxins with two major groups, Stx1 and Stx2, whose genes are considered to be part of the genome of lambdoid prophages. 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 serotype O157:H7 and other enterohemorrhagic E. coli.

Nomenclature
There are many terms that microbiologists use to describe Shiga toxin and differentiate between different forms of it. Many of these terms are used interchangeably. 1) Shiga toxin (Stx) - true Shiga toxin is produced by Shigella dysenteriae. 2) Shiga-like toxin 1 and 2 (SLT-1 and 2 or Stx-1 and 2) - the Shiga toxins produced by some E. coli strains. Stx-1 differs from Stx by only 1 amino acid. Stx-2 shares 56% sequence homology with Stx-1. 3) Cytotoxins - an archaic denotation for Stx, used in a broad sense. 4) Verocytotoxins - a seldom used denotation for Stx, 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 toxin produced by Ricinus communis. After entering a cell, the protein functions as an N-glycosidase, cleaving several nucleobases from the RNA that comprises the ribosome, thereby halting protein synthesis.

Structure
The toxin has two subunits&mdash;designated A and B&mdash;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 approximately 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.

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.