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bioRxiv · 10.64898/2026.09.22.753655

Marine sulfated glycans inhibit the binding of Borrelia burgdorferi adhesins to heparin/GAGs

Bu, C.·Xia, K.·Fernandes, C.·Lin, Y.-P.·Parveen, N.·Pomin, V. H.·Dordick, J. S.·Chi, L.·Zhang, F.
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Abstract

Recognition of host glycosaminoglycans (GAGs) is critical for the adhesion and colonization of Borrelia burgdorferi, but the structural requirements for these interactions remain incompletely understood. Using surface plasmon resonance (SPR), we characterized the heparin-binding properties of three Borrelia 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 (KD) of 2.18 nM for Bgp and 36.4 nM for DbpB-B31. Competition assays identified N-sulfation and 6-O-sulfation as major determinants of binding, whereas 2-O-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 Holothuria floridana was the most potent inhibitor of Bgp, with an IC50 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 B. burgdorferi-host GAG interactions.

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Bu, C., Xia, K., Fernandes, C., Lin, Y.-P., Parveen, N., Pomin, V. H., Dordick, J. S., Chi, L., Zhang, F.. 2026-09-23. Marine sulfated glycans inhibit the binding of Borrelia burgdorferi adhesins to heparin/GAGs. https://doi.org/10.64898/2026.09.22.753655

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