Human glycan expression patterns influence Group A streptococcal colonization of epithelial cells

FASEB J. 2019 Oct;33(10):10808-10818. doi: 10.1096/fj.201900559R. Epub 2019 Jun 29.

Abstract

Colonization of the oropharynx is the initial step in Group A Streptococcus (GAS) pharyngeal infection. We have previously reported that the highly virulent M1T1 GAS clone attaches to oral epithelial cells via M1 protein interaction with blood group antigen carbohydrate structures. Here, we have identified that colonization of human oral epithelial cells by GAS serotypes M3 and M12 is mediated by human blood group antigens [ABO(H)] and Lewis (Le) antigen expression. Removal of linkage-specific fucose, galactose, N-acetylgalactosamine, and sialic acid modulated GAS colonization, dependent on host ABO(H) blood group and Le expression profile. Furthermore, N-linked glycans from human salivary glycoproteins, when released and purified, were potent inhibitors of M1, M3, and M12 GAS colonization ex vivo. These data highlight the important role played by human protein glycosylation patterns in GAS attachment to oral epithelial cell surfaces.-De Oliveira, D. M. P., Everest-Dass, A., Hartley-Tassell, L., Day, C. J., Indraratna, A., Brouwer, S., Cleary, A., Kautto, L., Gorman, J., Packer, N. H., Jennings, M. P., Walker, M. J., Sanderson-Smith, M. L. Human glycan expression patterns influence Group A streptococcal colonization of epithelial cells.

Keywords: M protein; blood group antigens; glycosylation; pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Bacterial / physiology
  • Bacterial Adhesion / immunology
  • Bacterial Adhesion / physiology
  • Bacterial Outer Membrane Proteins / physiology
  • Blood Group Antigens / chemistry
  • Carrier Proteins / physiology
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Epithelial Cells / microbiology
  • Glycosylation
  • Host Microbial Interactions / immunology
  • Host Microbial Interactions / physiology*
  • Humans
  • In Vitro Techniques
  • Polysaccharides / chemistry
  • Polysaccharides / immunology
  • Polysaccharides / metabolism*
  • Protein Binding
  • Salivary Proteins and Peptides / chemistry
  • Salivary Proteins and Peptides / immunology
  • Salivary Proteins and Peptides / metabolism
  • Streptococcal Infections / etiology
  • Streptococcal Infections / microbiology
  • Streptococcus pyogenes / growth & development
  • Streptococcus pyogenes / pathogenicity*
  • Streptococcus pyogenes / physiology
  • Virulence / physiology

Substances

  • Antigens, Bacterial
  • Bacterial Outer Membrane Proteins
  • Blood Group Antigens
  • Carrier Proteins
  • Polysaccharides
  • Salivary Proteins and Peptides
  • streptococcal M protein