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 (125)I-Stx1 but not (125)I-Stx2 to the murine kidney and brain. A modified version of Starfish, called "Daisy," in which the Stx alpha Gal(1,4)beta Gal(1,4)beta Glc 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.
MeSH terms
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Animals
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Anti-Bacterial Agents / administration & dosage
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Anti-Bacterial Agents / therapeutic use*
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Antibodies, Bacterial / blood
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Antitoxins / therapeutic use*
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Carbohydrate Sequence
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Disease Models, Animal
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Double-Blind Method
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Escherichia coli Infections / blood
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Escherichia coli Infections / drug therapy*
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Escherichia coli Infections / etiology
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Escherichia coli* / immunology
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Female
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Hemolytic-Uremic Syndrome / blood
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Hemolytic-Uremic Syndrome / drug therapy*
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Hemolytic-Uremic Syndrome / etiology
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Immunoblotting
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Injections, Subcutaneous
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Mice
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Mice, Inbred BALB C
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Molecular Sequence Data
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Oligosaccharides / administration & dosage
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Oligosaccharides / chemistry
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Oligosaccharides / therapeutic use*
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Shiga Toxin 1 / antagonists & inhibitors
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Shiga Toxin 2 / antagonists & inhibitors
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Streptomycin / therapeutic use
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Treatment Outcome
Substances
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Anti-Bacterial Agents
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Antibodies, Bacterial
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Antitoxins
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Daisy carbohydrate
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Oligosaccharides
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STARFISH carbohydrate
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Shiga Toxin 1
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Shiga Toxin 2
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Streptomycin