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Fucose-Galactose Po...
Fucose-Galactose Polymers Inhibit Cholera Toxin Binding to Fucosylated Structures and Galactose-Dependent Intoxication of Human Enteroids.
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- Cervin, Jakob (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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- Boucher, Andrew, 1991 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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Youn, Gyusaang (author)
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- Björklund, Per (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för gastrokirurgisk forskning och utbildning,Institute of Clinical Sciences, Department of Gastrosurgical Research and Education
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- Wallenius, Ville, 1970 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för gastrokirurgisk forskning och utbildning,Institute of Clinical Sciences, Department of Gastrosurgical Research and Education
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- Mottram, Lynda (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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Sampson, Nicole S (author)
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- Yrlid, Ulf, 1971 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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(creator_code:org_t)
- 2020-03-05
- 2020
- English.
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In: ACS infectious diseases. - : American Chemical Society (ACS). - 2373-8227. ; 6:5, s. 1192-1203
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https://doi.org/10.1...
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Abstract
Subject headings
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- A promising strategy to limit cholera severity involves blockers mimicking the canonical cholera toxin ligand (CT) ganglioside GM1. However, to date the efficacies of most of these blockers have been evaluated in noncellular systems that lack ligands other than GM1. Importantly, the CT B subunit (CTB) has a noncanonical site that binds fucosylated structures, which in contrast to GM1 are highly expressed in the human intestine. Here we evaluate the capacity of norbornene polymers displaying galactose and/or fucose to block CTB binding to immobilized protein-linked glycan structures and also to primary human and murine small intestine epithelial cells (SI ECs). We show that the binding of CTB to human SI ECs is largely dependent on the noncanonical binding site, and interference with the canonical site has a limited effect while the opposite is observed with murine SI ECs. The galactose-fucose polymer blocks binding to fucosylated glycans but not to GM1. However, the preincubation of CT with the galactose-fucose polymer only partially blocks toxic effects on cultured human enteroid cells, while preincubation with GM1 completely blocks CT-mediated secretion. Our results support a model whereby the binding of fucose to the noncanonical site places CT in close proximity to scarcely expressed galactose receptors such as GM1 to enable binding via the canonical site leading to CT internalization and intoxication. Our finding also highlights the importance of complementing CTB binding studies with functional intoxication studies when assessing the efficacy inhibitors of CT.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Keyword
- cholera toxin
- fucose
- galactose; inhibition
- multivalent glycopolymer
- norbornene
Publication and Content Type
- ref (subject category)
- art (subject category)
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Cervin, Jakob
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Boucher, Andrew, ...
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Youn, Gyusaang
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Björklund, Per
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Wallenius, Ville ...
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Mottram, Lynda
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show more...
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Sampson, Nicole ...
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Yrlid, Ulf, 1971
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show less...
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and Basic Medicine
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MEDICAL AND HEAL ...
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and Basic Medicine
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MEDICAL AND HEAL ...
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ACS infectious d ...
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University of Gothenburg