Escherichia coli Shiga toxin.
The Stx family contains two types called Stx1 (verotoxin 1: VT1 or Shiga-like toxin: SLT1) and Stx2 (VT2, SLT2); both toxins are encoded by bacteriophages. Stx1 is identical to Shiga toxin produced by Shigella dysenteriae type I. Stx2 is heterogeneous and immunologically different from Stx1. Although many variations are found in Stx family, all Stx has an A-B structure: the A subunit has N-glycosidase activity and the B subunit binds to a membrane glycolipid, globotriaosylceramide (Gb3). The A subunit cleaves a single adenine residue from the 28S rRNA component of eukaryotic ribosomes, resulting in inhibition of protein synthesis. Stx-producing Escherichia coli (STEC) is known to cause hemorrhagic enterocolitis and hemolytic-uremic syndrome (HUS). Stx plays a role in the occurrence of blood in the feces and in the HUS by their action on the endothelial cells of blood vessels in the intestinal submucosa and in the renal glomeruli. Epidemiologically, Stx2 seems to be more important than Stx1 in development of HUS. The action of Stx is not limited to inhibition of protein synthesis. Stx induces macrophages to express tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) in vitro. These cytokines and lipopolysaccharide (LPS) are reported to increase the susceptibility of cells to Stx. A variety of cells such as tubular epithelial cells, may be targets for Stx-mediated apoptosis. Apoptosis is considered to contribute to the pathogenesis of HUS caused by STEC. In this review, recent progress in Stx-related research is summarized.
Nakao
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H
Department of Infectious Diseases Research, National Children's Medical Research Center, National Children's Hospital, Tokyo, Japan. hnakao@nch.go.jp
Takeda
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T
D017209:Apoptosis / Q000187:drug effects*; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects; D004705:Endocytosis; D004760:Enterocolitis / Q000503:physiopathology; D004926:Escherichia coli / Q000737:chemistry / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000503:physiopathology*; D006463:Hemolytic-Uremic Syndrome / Q000503:physiopathology*; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D014176:Protein Biosynthesis; D022621:Shiga Toxin / Q000494:pharmacology* / Q000633:toxicity
D016207:Cytokines; D022621:Shiga Toxin