Poster Presentation BACPATH 2017

Glycan-glycan interactions between host and bacterial surface glycosylation: Role in first contact between host and pathogens (#115)

Christopher J Day 1 , Tsitsi Mubaiwa 1 , Evgeny Semchenko 1 , Elizabeth N. H. Tran 2 , Thomas Haselhorst 1 , Kate Seib 1 , Renato Morona 2 , Michael Jennings 1
  1. Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia
  2. Department of Molecular and Cellular Biology, University of Adelaide, Adelaide, South Australia, Australia

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.