Cells from all domains of life express surface carbohydrates, which are typically linked to protein or lipid and are known as glycans. Cell-to-cell contact, mediated by glycan-glycan interactions is considered insignificant with research focused primarily on protein-glycan or protein-protein interactions1-3.
It has recently been shown in four Gram-negative bacteria that the lipooligo/polysaccharide (LOS/LPS) on the bacterial surface can directly bind host glycans with high affinity and are important in the adherence to host cells. By screening the LOS/LPS of Campylobacter jejuni, Shigella flexneri, Salmonella typhimurium, and Haemophilus influenzae we identified >300 different glycan-glycan interactions (by glycan array) and verified 66 pairs using surface plasmon resonance (SPR) and isothermal calorimetry (ITC). The highest affinity interaction identified in this study was between human blood group B antigen and the molecular mimic of asialo GM1 produced by C. jejuni with a dissociation constant (KD) of ~100nM (140nM by SPR; 98nM by ITC)4.
We have now screened a range of polysaccharides of several other pathogens including Neisseria spp. and Pseudomonas aeruginosa using glycan array, identifying a further ~200 novel glycan-glycan interactions. This screen has identified the highest affinity glycan-glycan interaction observed so far, with the KD between the LPS of N. meningitidis and Thomsen–Friedenreich antigen of 13nM5.
To date only very limited structural information about glycan-glycan interactions is available. Using a wide range of multidisciplinary techniques including molecular modelling and nuclear magnetic resonance, we attempt to elucidate glycan-glycan structures at an atomic level.
We have shown that high affinity glycan-glycan interactions between bacterial pathogens and the host are wide-spread. The highest affinity interactions are between bacterial host mimicking structures and host glycans. Here we also propose a role for glycan-glycan interactions in viral pathogens. Glycan-glycan interactions are a new paradigm in interactions between these ubiquitous biomolecules in biological systems.