Poster Presentation Lancefield International Symposium for Streptococci and Streptococcal Diseases 2025

Molecular dissection of Streptococcus suis surface glycans reveals conserved glycan motifs with implications in vaccine development (#312)

Yao Shi 1 2 , Göran Widmalm 3 , Charlotte Sorieul 4 , Thomas J Roodsant 1 , Jeff S Rush 5 , Natalia Korotkova 5 , Ton AC Jacobs 6 , Jeroen DC Codée 4 , Arjan Stegeman 2 , Constance Schultsz 1 , Lindert Benedictus 2 , Nina M. van Sorge 1
  1. Amsterdam University Medical Centers, Amsterdam, NA, Netherlands
  2. Population Health Sciences, Utrecht University, Utrecht, Netherlands
  3. Organic Chemistry, Stockholm University, Stockholm, Sweden
  4. Leiden Institute of Chemistry, Leiden University, Leiden , Netherlands
  5. Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, United States
  6. MSD Animal Health, Boxmeer, Netherlands

Streptococcus suis (S. suis) is a genetically diverse pathogen and a global cause of severe infections, e.g. sepsis and meningitis, in pigs and humans after zoonotic transmission. The development of a broadly protective vaccine would reduce the substantial economic burden, disease, and antibiotic use in livestock. Rhamnose-rich polysaccharides (RPS), such as the Group A Carbohydrate of Streptococcus pyogenes, are important surface structures and attractive vaccine targets. Here we identified the 14-gene S. suis RPS biosynthesis gene cluster (srpBCDEGIJKLMNPQR; SSU11241111) and characterized two structural RPS variants that are expressed by pathogenic S. suis. The RPS structures of S. suis S10 and 861160 were elucidated by a combination of lectin staining, glycan composition analysis and NMR. Both structures consisted of a heptasaccharide repeating unit but displayed structural variation (i.e. a galactose or glucose moiety) in the sidechain through genetic variation in srpL. Similar to S. pyogenes, the sidechain was partially substituted with glycerol phosphate, which required the gene SSU1125 flanking the 14-gene cluster. In both strains, the glycosyltransferase encoded by srpP was essential for sidechain biosynthesis. Isogenic S. suis mutants of srpP and srpL displayed morphological alterations and increased lysozyme resistance. Importantly, a glycoconjugate of the ΔsrpL RPS, consisting of the conserved hexasaccharide, elicited IgG antibodies in pigs that exhibited cross-reactivity with both RPS structural variants and S. suis strains from various genetic backgrounds. Thus, S. suis RPS is important for physiology and host interaction, and contains a conserved glycan motif that should be further explored as broadly protective vaccine antigen.