Journal Article

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 and Glen D Armstrong

in The Journal of Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 187, issue 4, pages 640-649
Published in print February 2003 | ISSN: 0022-1899
Published online February 2003 | e-ISSN: 1537-6613 | DOI: http://dx.doi.org/10.1086/373996
Assessment in Mice of the Therapeutic Potential of Tailored, Multivalent Shiga Toxin Carbohydrate Ligands

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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

Journal Article.  7358 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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