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Toxins 2013, 5(11), 2074-2092; doi:10.3390/toxins5112074

Shiga Toxin Type 2dact Displays Increased Binding to Globotriaosylceramide in vitro and Increased Lethality in Mice after Activation by Elastase

Department of Microbiology and Immunology, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD 20814, USA
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Received: 29 August 2013 / Revised: 31 October 2013 / Accepted: 4 November 2013 / Published: 8 November 2013
(This article belongs to the Special Issue Novel Properties of Well-Characterized Toxins)
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Abstract

Shiga toxin type 2dact (Stx2dact), an Stx2 variant originally identified from Escherichia coli O91:H21 strain B2F1, displays increased cytotoxicity after activation by elastase present in intestinal mucus. Activation is a result of cleavage of two amino acids from the C-terminal tail of the A2 subunit. In this study, we hypothesized that activation leads to increased binding of toxin to its receptor on host cells both in vitro and in vivo. To test this theory, Stx2dact was treated with elastase or buffer alone and then each toxin was assessed for binding to purified globotriaosylceramide (Gb3) in an enzyme-linked immunosorbent assay, or cells in culture by immunofluorescence, or flow cytometry. Elastase- and buffer-treated Stx2dact were also evaluated for binding to mouse kidney tissue and for relative lethality in mice. We found that activated Stx2dact had a greater capacity to bind purified Gb3, cells in culture, and mouse kidney tissue and was more toxic for mice than was non-activated Stx2dact. Thus, one possible mechanism for the augmented cytotoxicity of Stx2dact after activation is its increased capacity to bind target cells, which, in turn, may cause greater lethality of elastase-treated toxin for mice and enhanced virulence for humans of E. coli strains that express Stx2dact. View Full-Text
Keywords: Shiga toxin 2d; Stx2dact; globotriaosylceramide/Gb3; Stx2dact binding; Stx2dact A2 subunit Shiga toxin 2d; Stx2dact; globotriaosylceramide/Gb3; Stx2dact binding; Stx2dact A2 subunit
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Bunger, J.C.; Melton-Celsa, A.R.; O'Brien, A.D. Shiga Toxin Type 2dact Displays Increased Binding to Globotriaosylceramide in vitro and Increased Lethality in Mice after Activation by Elastase. Toxins 2013, 5, 2074-2092.

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