title: Glycan:glycan interactions: High affinity biomolecular interactions that can mediate binding of pathogenic bacteria to host cells.
abstract: Cells from all domains of life express glycan structures attached to lipids and proteins on their surface, called glycoconjugates. Cell-to-cell contact mediated by glycan:glycan interactions have been considered to be low-affinity interactions that precede high-affinity protein-glycan or protein-protein interactions. In several pathogenic bacteria, truncation of surface glycans, lipooligosaccharide (LOS), or lipopolysaccharide (LPS) have been reported to significantly reduce bacterial adherence to host cells. Here, we show that the saccharide component of LOS/LPS have direct, high-affinity interactions with host glycans. Glycan microarrays reveal that LOS/LPS of four distinct bacterial pathogens bind to numerous host glycan structures. Surface plasmon resonance was used to determine the affinity of these interactions and revealed 66 high-affinity host-glycan:bacterial-glycan pairs with equilibrium dissociation constants (K(D)) ranging between 100 nM and 50 µM. These glycan:glycan affinity values are similar to those reported for lectins or antibodies with glycans. Cell assays demonstrated that glycan:glycan interaction-mediated bacterial adherence could be competitively inhibited by either host cell or bacterial glycans. This is the first report to our knowledge of high affinity glycan:glycan interactions between bacterial pathogens and the host. The discovery of large numbers of glycan:glycan interactions between a diverse range of structures suggests that these interactions may be important in all biological systems.
authors.affiliation: Institute for Glycomics, Griffith University Gold Coast Campus, Gold Coast, QLD 4222, Australia; c.day@griffith.edu.au m.jennings@griffith.edu.au.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Day
authors.affiliation: School of Biological Sciences, Department of Molecular and Cellular Biology, University of Adelaide, Adelaide, SA 5005, Australia;
authors.forename: Elizabeth N
authors.initials: EN
authors.lastname: Tran
authors.affiliation: Institute for Glycomics, Griffith University Gold Coast Campus, Gold Coast, QLD 4222, Australia;
authors.forename: Evgeny A
authors.initials: EA
authors.lastname: Semchenko
authors.affiliation: Institute for Glycomics, Griffith University Gold Coast Campus, Gold Coast, QLD 4222, Australia;
authors.forename: Greg
authors.initials: G
authors.lastname: Tram
authors.affiliation: Institute for Glycomics, Griffith University Gold Coast Campus, Gold Coast, QLD 4222, Australia;
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Hartley-Tassell
authors.affiliation: Institute for Glycomics, Griffith University Gold Coast Campus, Gold Coast, QLD 4222, Australia;
authors.forename: Preston S K
authors.initials: PS
authors.lastname: Ng
authors.affiliation: Institute for Glycomics, Griffith University Gold Coast Campus, Gold Coast, QLD 4222, Australia;
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: King
authors.affiliation: Institute for Glycomics, Griffith University Gold Coast Campus, Gold Coast, QLD 4222, Australia;
authors.forename: Rachel
authors.initials: R
authors.lastname: Ulanovsky
authors.affiliation: Institute for Glycomics, Griffith University Gold Coast Campus, Gold Coast, QLD 4222, Australia;
authors.forename: Sarah
authors.initials: S
authors.lastname: McAtamney
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, IA 52242.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Apicella
authors.affiliation: Institute for Glycomics, Griffith University Gold Coast Campus, Gold Coast, QLD 4222, Australia;
authors.forename: Joe
authors.initials: J
authors.lastname: Tiralongo
authors.affiliation: School of Biological Sciences, Department of Molecular and Cellular Biology, University of Adelaide, Adelaide, SA 5005, Australia;
authors.forename: Renato
authors.initials: R
authors.lastname: Morona
authors.affiliation: Institute for Glycomics, Griffith University Gold Coast Campus, Gold Coast, QLD 4222, Australia;
authors.forename: Victoria
authors.initials: V
authors.lastname: Korolik
authors.affiliation: Institute for Glycomics, Griffith University Gold Coast Campus, Gold Coast, QLD 4222, Australia; c.day@griffith.edu.au m.jennings@griffith.edu.au.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Jennings
mesh_terms: D001422:Bacterial Adhesion; D018938:Caco-2 Cells; D002151:Calorimetry / Q000379:methods; D016123:Campylobacter jejuni / Q000378:metabolism / Q000502:physiology; D006001:Glycoconjugates / Q000378:metabolism*; D006193:Haemophilus influenzae / Q000378:metabolism / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D007082:Ileum / Q000378:metabolism / Q000382:microbiology; D008070:Lipopolysaccharides / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000378:metabolism / Q000502:physiology; D012763:Shigella flexneri / Q000378:metabolism / Q000502:physiology; D020349:Surface Plasmon Resonance; D013816:Thermodynamics
chemical_list: D006001:Glycoconjugates; D008070:Lipopolysaccharides; D011134:Polysaccharides; C023023:lipid-linked oligosaccharides
keywords: adherence; glycoconjugates; lipooligosaccharide; lipopolysccharide