Assessment in mice of the therapeutic potential of tailored, multivalent Shiga toxin carbohydrate ligands

George L. Mulvey; Paola Marcato; Pavel I. Kitov; Joanna Sadowska; David R. Bundle; Glen D. Armstrong

doi:10.1086/373996

Assessment in mice of the therapeutic potential of tailored, multivalent Shiga toxin carbohydrate ligands

George L. Mulvey, Paola Marcato, Pavel I. Kitov, Joanna Sadowska, David R. Bundle, Glen D. Armstrong

Research output: Contribution to journal › Article › peer-review

143 Citations (Scopus)

Abstract

The therapeutic potential of 2 soluble multivalent receptor-based inhibitors of Shiga toxin (Stx) 1 and Stx2 was determined in mice. One of these, Starfish, protected mice when it was injected subcutaneously in admixture with a lethal dose of Stx1 but not Stx2. Starfish also reduced the distribution of ¹²⁵I-Stx1 but not ¹²⁵I-Stx2 to the murine kidney and brain. A modified version of Starfish, called "Daisy," in which the Stx αGal(1,4)βGal(1,4)βGlc receptors were installed on the core glucose structure via a modified tethering strategy, protected mice against both Stx1 and Stx2. Daisy also protected streptomycin-treated mice from Escherichia coli O91:H21 and did not interfere with the ability of the murine immune system to produce Stx-specific protective antibodies. These results extend the possibility of using soluble carbohydrate-based receptor inhibitors to prevent Stx-mediated complications arising from infections with enterohemorrhagic E. coli serotypes.

Original language	English
Pages (from-to)	640-649
Number of pages	10
Journal	Journal of Infectious Diseases
Volume	187
Issue number	4
DOIs	https://doi.org/10.1086/373996
Publication status	Published - Feb 15 2003
Externally published	Yes

Bibliographical note

Funding Information:
Financial support: Canadian Institutes for Health Research (MWS 56081 to G.D.A.); Canadian Bacterial Diseases Network (VP 17 to G.D.A. and D1 to D.R.B.). P.M. was the recipient of graduate studentships from the Canadian Institutes for Health Research and the Alberta Heritage Foundation for Medical Research, a Meredith Graduate Fellowship administered by the Worker’s Compensation Board of Alberta, and a bursary from the British Columbia Cattleman’s Association.

ASJC Scopus Subject Areas

Immunology and Allergy
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1086/373996

Cite this

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abstract = "The therapeutic potential of 2 soluble multivalent receptor-based inhibitors of Shiga toxin (Stx) 1 and Stx2 was determined in mice. One of these, Starfish, protected mice when it was injected subcutaneously in admixture with a lethal dose of Stx1 but not Stx2. Starfish also reduced the distribution of 125I-Stx1 but not 125I-Stx2 to the murine kidney and brain. A modified version of Starfish, called {"}Daisy,{"} in which the Stx αGal(1,4)βGal(1,4)βGlc receptors were installed on the core glucose structure via a modified tethering strategy, protected mice against both Stx1 and Stx2. Daisy also protected streptomycin-treated mice from Escherichia coli O91:H21 and did not interfere with the ability of the murine immune system to produce Stx-specific protective antibodies. These results extend the possibility of using soluble carbohydrate-based receptor inhibitors to prevent Stx-mediated complications arising from infections with enterohemorrhagic E. coli serotypes.",

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Assessment in mice of the therapeutic potential of tailored, multivalent Shiga toxin carbohydrate ligands

Abstract

Bibliographical note

ASJC Scopus Subject Areas

UN SDGs

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