Shigella toxin and the pathogenesis of shigellosis.
Shigella dysenteriae 1 produces a periplasmic protein with multiple toxic effects in vivo and in vitro. These include neurotoxicity, cytotoxicity and enterotoxicity, as well as the ability to inhibit cell-free protein synthesis. The purified toxin is a protein of relative molecular mass (Mr) 64 000. It is composed of one catalytically active A subunit (Mr = 32 000) that inhibits protein synthesis, and a complex of five B monomers (Mr approximately 6500 each). Studies using subunit-specific antibodies demonstrate that the B subunit mediates the binding of toxin to toxin receptors in the cell membrane. In a model system in HeLa cell culture, the surface membrane receptor has been shown to be a glycoprotein, most probably asparagine-linked, and to contain oligomeric beta 1----4 linked N-acetyl-D-glucosamine. Studies with metabolic inhibitors and agents that disrupt the cytoskeleton, and/or alter the pH and function of acidic cytoplasmic vesicles, provide indirect evidence that toxin is transported from the cell surface to the cell interior. This process is probably receptor-mediated endocytosis, since it is also inhibited by amines that prevent receptor-mediated uptake of other ligands in well-characterized systems. The toxic action in the HeLa cell is due to the subsequent inhibition of protein synthesis which results from catalytic inactivation of the 60S ribosomal subunit and the cessation of polypeptide chain elongation. Inhibition of protein synthesis by toxin produced subsequent to bacterial invasion of colonic epithelial cells could explain the destructive lesions found in shigellosis. Although toxin can induce jejunal secretion in animal models, there is at present no clear explanation for the secretory response of the gut mucosa in shigella infection.
D000818:Animals; D001427:Bacterial Toxins / Q000302:isolation & purification / Q000378:metabolism / Q000633:toxicity*; D002462:Cell Membrane / Q000378:metabolism; D004405:Dysentery, Bacillary / Q000382:microbiology*; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D008954:Models, Biological; D008970:Molecular Weight; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000378:metabolism; D022603:Shiga Toxins; D012760:Shigella / Q000472:pathogenicity*
D001427:Bacterial Toxins; D046911:Macromolecular Substances; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D022603:Shiga Toxins; C045390:shigella toxin receptor