{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:21:15Z","timestamp":1787008875663,"version":"build-2736575974"},"reference-count":71,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T00:00:00Z","timestamp":1692921600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2017\u20132646"],"award-info":[{"award-number":["2017\u20132646"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM090271"],"award-info":[{"award-number":["R01GM090271"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35GM145599"],"award-info":[{"award-number":["R35GM145599"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Prior research on cholera toxin (CT) binding and intoxication has relied on human colonic cancer derived epithelial cells. While these transformed cell lines have been beneficial, they neither derive from small intestine where intoxication occurs, nor represent the diversity of small intestinal epithelial cells (SI-ECs) and variation in glycoconjugate expression among individuals. Here, we used human enteroids, derived from jejunal biopsies of multipledonors to study CT binding and intoxication of human non-transformed SI-ECs. We modulated surface expression of glycosphingolipids, glycoproteins and specific glycans to distinguish the role of each glycan\/glycoconjugate. Cholera-toxin-subunit-B (CTB) mutants were generated to decipher the preference of each glycoconjugate to different binding sites and the correlation between CT binding and intoxication. Human enteroids contain trace amounts of GM1, but other glycosphingolipids may be contributing to CT intoxication. We discovered that inhibition of either fucosylation or O-glycosylation sensitize enteroids to CT-intoxication. This can either be a consequence of the removal of fucosylated \u201cdecoy-like-ligands\u201d binding to CTB\u2019s non-canonical site and\/or increase in the availability of Gal\/GalNAc-terminating glycoconjugates binding to the canonical site. Furthermore, simultaneous inhibition of fucosylation and O-glycosylation increased the availability of additional Gal\/GalNAc-terminating glycoconjugates but counteracted the sensitization in CT intoxication caused by inhibiting O-glycosylation because of reduction in fucose. This implies a dual role of fucose as a functional glycan and a decoy, the interplay of which influences CT binding and intoxication. Finally, while the results were similar for enteroids from different donors, they were not identical, pointing to a role for human genetic variation in determining sensitivity to CT.<\/jats:p>","DOI":"10.1093\/glycob\/cwad069","type":"journal-article","created":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T08:55:12Z","timestamp":1692867312000},"page":"801-816","source":"Crossref","is-referenced-by-count":11,"title":["Cholera intoxication of human enteroids reveals interplay between decoy and functional glycoconjugate ligands"],"prefix":"10.1093","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2139-7954","authenticated-orcid":false,"given":"Akshi","family":"Singla","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology , Institute of Biomedicine, , Medicinaregatan 1G, 41390 Gothenburg , Sweden"},{"name":"University of Gothenburg , Institute of Biomedicine, , Medicinaregatan 1G, 41390 Gothenburg , Sweden"},{"name":"Department of Medical Chemistry and Cell Biology , Institute of Biomedicine, , Medicinaregatan 1G, 41390 Gothenburg , Sweden"},{"name":"University of Gothenburg , Institute of Biomedicine, , Medicinaregatan 1G, 41390 Gothenburg , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4237-4612","authenticated-orcid":false,"given":"Andrew","family":"Boucher","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology , Institute of Biomedicine, , Medicinaregatan 1G, 41390 Gothenburg , Sweden"},{"name":"University of Gothenburg , Institute of Biomedicine, , Medicinaregatan 1G, 41390 Gothenburg , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2842-1275","authenticated-orcid":false,"given":"Kerri-Lee","family":"Wallom","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Oxford , Mansfield Road, Oxford OX1 3QT , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9458-9474","authenticated-orcid":false,"given":"Michael","family":"Lebens","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology , Institute of Biomedicine, , Medicinaregatan 1G, 41390 Gothenburg , Sweden"},{"name":"University of Gothenburg , Institute of Biomedicine, , Medicinaregatan 1G, 41390 Gothenburg , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5373-3329","authenticated-orcid":false,"given":"Jennifer J","family":"Kohler","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Texas Southwestern Medical Center , 5323 Harry Hines Blvd., Dallas, TX 75390-9185 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7614-0403","authenticated-orcid":false,"given":"Frances M","family":"Platt","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Oxford , Mansfield Road, Oxford OX1 3QT , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3431-6770","authenticated-orcid":false,"given":"Ulf","family":"Yrlid","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology , Institute of Biomedicine, , Medicinaregatan 1G, 41390 Gothenburg , Sweden"},{"name":"University of Gothenburg , Institute of Biomedicine, , Medicinaregatan 1G, 41390 Gothenburg , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,8,25]]},"reference":[{"issue":"2","key":"2023110719280926200_ref1","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1093\/oxfordjournals.jbchem.a123736","article-title":"Improved inhibitors of glucosylceramide 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