Oral Presentation BacPath 13: Molecular Analysis of Bacterial Pathogens Conference 2015

Glycan:glycan interactions: A new paradigm in biomolecular interactions that can mediate binding of pathogenic bacteria to host cells (#4)

Christopher Day 1 , Elizabeth N. H. Tran 2 , Evgeny Semchenko 1 , Greg Tram 1 , Lauren Hartley-Tassell 1 , Preston Ng 1 , Rebecca King 1 , Rachel Ulanovsky 1 , Sarah McAtamney 1 , Michael Apicella 3 , Joe Tiralongo 1 , Renato Morona 2 , Victoria Korolik 1 , Michael Jennings 1
  1. Institute for Glycomics, Griffith University, Gold Coast, QLD, Australia
  2. Department of Molecular and Cellular Biology, University of Adelaide, Adelaide, SA, Australia
  3. Department of Microbiology, University of Iowa, Iowa City, IA, United States

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; Campylobacter jejuni, Shigella flexneri, Salmonella typhimurium, and Haemophilus influenzae; bind to a range of host glycan structures. Interactions with host pathogens included blood group antigens, Lewis antigens and glycosaminoglycans for all for pathogens tested. Surface plasmon resonance data confirmed binding between 41 different host-glycan:bacterial-glycan pairs with affinities of 100 nM-100 ┬ÁM, demonstrating that glycan:glycan interactions have an affinity range similar to those of 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 of high affinity glycan:glycan interactions between bacterial pathogens and the host, and defines a new paradigm in interactions between these ubiquitous biomolecules in biological systems.