Shiga Toxin Subtypes Display Dramatic Differences in Potency
- 1 March 2011
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 79 (3), 1329-1337
- https://doi.org/10.1128/iai.01182-10
Abstract
Purified Shiga toxin (Stx) alone is capable of producing systemic complications, including hemolytic-uremic syndrome (HUS), in animal models of disease. Stx includes two major antigenic forms (Stx1 and Stx2), with minor variants of Stx2 (Stx2a to -h). Stx2a is more potent than Stx1. Epidemiologic studies suggest that Stx2 subtypes also differ in potency, but these differences have not been well documented for purified toxin. The relative potencies of five purified Stx2 subtypes, Stx2a, Stx2b, Stx2c, Stx2d, and activated (elastase-cleaved) Stx2d, were studied in vitro by examining protein synthesis inhibition using Vero monkey kidney cells and inhibition of metabolic activity (reduction of resazurin to fluorescent resorufin) using primary human renal proximal tubule epithelial cells (RPTECs). In both RPTECs and Vero cells, Stx2a, Stx2d, and elastase-cleaved Stx2d were at least 25 times more potent than Stx2b and Stx2c. In vivo potency in mice was also assessed. Stx2b and Stx2c had potencies similar to that of Stx1, while Stx2a, Stx2d, and elastase-cleaved Stx2d were 40 to 400 times more potent than Stx1.Keywords
This publication has 54 references indexed in Scilit:
- Role of Tumor Necrosis Factor Alpha in Disease Using a Mouse Model of Shiga Toxin-Mediated Renal DamageInfection and Immunity, 2010
- Different Classes of Antibiotics Differentially Influence Shiga Toxin ProductionAntimicrobial Agents and Chemotherapy, 2010
- Glycan Encapsulated Gold Nanoparticles Selectively Inhibit Shiga Toxins 1 and 2Bioconjugate Chemistry, 2010
- Distinct Physiologic and Inflammatory Responses Elicited in Baboons after Challenge with Shiga Toxin Type 1 or 2 from Enterohemorrhagic Escherichia coliInfection and Immunity, 2010
- Comparison of Binding Platforms Yields Insights into Receptor Binding Differences between Shiga Toxins 1 and 2Biochemistry, 2010
- Shiga Toxin 2 Targets the Murine Renal Collecting Duct EpitheliumInfection and Immunity, 2009
- Shiga toxin-2 results in renal tubular injury but not thrombotic microangiopathy in heterozygous factor H-deficient miceClinical and Experimental Immunology, 2008
- Identification and Characterization of Shiga Toxin Type 2 Variants in Escherichia coli Isolates from Animals, Food, and HumansApplied and Environmental Microbiology, 2008
- Variation in virulence among clades of Escherichia coli O157:H7 associated with disease outbreaksProceedings of the National Academy of Sciences, 2008
- Subtyping Method for Escherichia coli Shiga Toxin (Verocytotoxin) 2 Variants and Correlations to Clinical ManifestationsJournal of Clinical Microbiology, 2007