Cells from all domains of life express surface carbohydrates, these protein and lipid linked sugars are known as glycans. Cell-to-cell contact mediated by glycan-glycan interactions have for decades been considered insignificant with research focused primarily on protein-glycan or protein-protein interactions.
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 that have affinities on par with protein-glycan interactions using surface plasmon resonance (SPR) and isothermal calorimetry (ITC). The highest affinity interaction identified in this study was between the blood group B antigen of humans and the molecular mimic of asialoGM1 produced by C. jejuni with a dissociation constant of ~100nM (140nM by SPR; 98nM by ITC).
We have now screened a range of bacterial polysaccharides of several other pathogenic bacteria 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 affinity between the LPS of N. meningitidis and Thomsen–Friedenreich antigen of 13nM.
To date only very limited structural information about glycan-glycan interactions is available. Using the wide range of glycan-glycan interactions we have identified, we are utilizing multidisciplinary techniques including molecular modeling and nuclear magnetic resonance in an 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 with these data providing further evidence that glycan-glycan interactions are a new paradigm in interactions between these ubiquitous biomolecules in biological systems.