{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T15:00:32Z","timestamp":1790434832247,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,23]]},"group-title":"Biochemistry","reference-count":30,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"funder":[{"award":["S10OD028523 and S10OD032168"],"award-info":[{"award-number":["S10OD028523 and S10OD032168"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Recognition of host glycosaminoglycans (GAGs) is critical for the adhesion and colonization of\n                  <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                  , but the structural requirements for these interactions remain incompletely understood. Using surface plasmon resonance (SPR), we characterized the heparin-binding properties of three\n                  <jats:italic>Borrelia<\/jats:italic>\n                  adhesins, i.e. Bgp, DbpA-A9, and DbpB-B31 and evaluated inhibitors comprising heparin oligosaccharides, selectively desulfated heparins, mammalian GAGs, marine sulfated glycans, pentosan polysulfate (PPS), and mucopolysaccharide polysulfate (MPS). All three adhesins bound directly to heparin, with equilibrium dissociation constants (\n                  <jats:italic>\n                    K\n                    <jats:sub>D<\/jats:sub>\n                  <\/jats:italic>\n                  ) of 2.18 nM for Bgp and 36.4 nM for DbpB-B31. Competition assays identified\n                  <jats:italic>N-<\/jats:italic>\n                  sulfation and 6-\n                  <jats:italic>O<\/jats:italic>\n                  -sulfation as major determinants of binding, whereas 2-\n                  <jats:italic>O<\/jats:italic>\n                  -sulfation had a lower effect. Bgp showed chain-length dependence over dp4-dp20, whereas DbpB-B31 preferentially recognized longer oligosaccharides, particularly those of dp12 or greater. Chondroitin sulfate E also exhibited strong inhibitory activity, indicating that recognition was not restricted to heparin\/heparan sulfate backbones. Among the tested sulfated glycans, fucosylated chondroitin sulfate (HfFucCS) from\n                  <jats:italic>Holothuria floridana<\/jats:italic>\n                  was the most potent inhibitor of Bgp, with an IC\n                  <jats:sub>50<\/jats:sub>\n                  of approximately 4 ng\/mL, whereas PPS was the strongest inhibitor of DbpB-B31, followed by MPS. These findings reveal protein-specific sulfated-glycan recognition and identify promising candidates for disrupting\n                  <jats:italic>B. burgdorferi<\/jats:italic>\n                  -host GAG interactions.\n                <\/jats:p>","DOI":"10.64898\/2026.09.22.753655","type":"posted-content","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:45:12Z","timestamp":1790185512000},"source":"Crossref","is-referenced-by-count":0,"title":["Marine sulfated glycans inhibit the binding of\n                  <i>Borrelia burgdorferi<\/i>\n                  adhesins to heparin\/GAGs"],"prefix":"10.64898","author":[{"given":"Changkai","family":"Bu","sequence":"first","affiliation":[{"name":"National Glycoengineering Research Center, Shandong University, Qingdao, Shandong Province, 266237, China"},{"name":"Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carly","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, 01536, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5240-2031","authenticated-orcid":false,"given":"Yi-Pin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, 01536, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikhat","family":"Parveen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ 07103, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitor H.","family":"Pomin","sequence":"additional","affiliation":[{"name":"Department of BioMolecular Sciences, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, Oxford, MS 38677, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan S.","family":"Dordick","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianli","family":"Chi","sequence":"additional","affiliation":[{"name":"National Glycoengineering Research Center, Shandong University, Qingdao, Shandong Province, 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092607350650000_2026.09.22.753655v1.1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.11.6279-6286.2004"},{"issue":"4","key":"2026092607350650000_2026.09.22.753655v1.2","doi-asserted-by":"crossref","first-page":"101207","DOI":"10.1016\/j.jbc.2021.101207","article-title":"Structural and kinetic analyses of holothurian sulfated 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