Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 189, Issue 3, Pages 360-368Publisher
OXFORD UNIV PRESS INC
DOI: 10.1086/381124
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Shiga toxin (Stx) is a major virulence factor in infection with Stx-producing Escherichia coli (STEC). We developed a series of linear polymers of acrylamide, each with a different density of trisaccharide of globotriaosylceramide (Gb(3)), which is a receptor for Stx, and identified Gb(3) polymers with highly clustered trisaccharides as Stx adsorbents functioning in the gut. The Gb(3) polymers specifically bound to both Stx1 and Stx2 with high affinity and markedly inhibited the cytotoxic activities of these toxins. Oral administration of the Gb(3) polymers protected mice after administration of a fatal dose of E. coli O157: H7, even when the polymers were administered after the infection had been established. In these mice, the serum level of Stx was markedly reduced and fatal brain damage was substantially suppressed, which suggests that the Gb(3) polymers entrap Stx in the gut and prevent its entrance into the circulation. These results indicate that the Gb(3) polymers can be used as oral therapeutic agents that function in the gut against STEC infections.
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