Virtual Poster 21st Lancefield International Symposium for Streptococci and Streptococcal Diseases 2022

Salivary glycan dynamics during experimental human Streptococcus pyogenes pharyngitis (#203)

Anuk Indraratna 1 2 , Arun Everest-Dass 3 , Joshua Osowicki 4 5 6 , Andrew Steer 4 5 6 , Danielle Skropeta 1 2 , Martina Sanderson-Smith 1 2
  1. Illawarra Health and Medical Research Institute, Wollongong, New South Wales, Australia
  2. Molecular Horizons, School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, New South Wales, Australia
  3. Institute for Glycomics, Griffith University, Southport, Queensland, Australia
  4. Tropical Diseases, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
  5. Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
  6. Infectious Diseases Unit, Department of General Medicine, The Royal Children's Hospital Melbourne, Melbourne, Victoria, Australia

Background:

Glycomics is the study of carbohydrates, or glycans, within a cell, tissue, or organism. New technologies have brought the human glycome into view and are beginning to reveal the role of glycans in host-pathogen interactions. The oropharyngeal niche of Streptococcus pyogenes is rich in glycans, some implicated in innate immune responses. Using a time-course approach, we characterised the dynamic oropharyngeal glycoprofile in saliva during experimental human pharyngitis with emm75 S. pyogenes (CHIVAS-M75 study).  

Methods:

Baseline, acute, and convalescent saliva samples were collected from healthy adult participants challenged with emm75 S. pyogenes. Qualitative and quantitative analysis of N- and O-glycans extracted from saliva was performed by porous graphitised carbon liquid chromatography coupled with electrospray ionisation tandem mass spectrometry (PGC-LC-ESI-MS/MS; LC-MS).

Results:

Of 145 N-glycans detected in saliva, 108 have been structurally solved or predicted from elution profiles and MS2 analyses. The majority (60%) are complex N-glycans. Preliminary time-course analyses from 3 patients reveal changes in the glycoprofile 48-hours post infection. The major change is an increase in N-glycans bearing neuraminic (sialic) acid, which has a well-recognised role in the innate immune response. This effect is mediated primarily by complex, doubly-sialylated structures.

Conclusion:

The host glycome is an important research target for efforts to understand host-pathogen interactions in streptococcal pharyngitis, and these findings will be validated in a larger cohort of human challenge trial participants. The observed sialic acid response suggests it may have an important role in triggering innate immune responses to S. pyogenes mucosal infections.