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

David M. P. De Oliveira, Arun Everest-Dass, Lauren Hartley-Tassell, Christopher J. Day, Anuk Indraratna, Stephan Brouwer, Ailish Cleary, Liisa Kautto, Jody Gorman, Nicolle H. Packer, Michael P. Jennings, Mark J. Walker, Martina L. Sanderson-Smith

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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.

Original languageEnglish
Pages (from-to)10808-10818
Number of pages11
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume33
Issue number10
DOIs
Publication statusPublished - Oct 2019

Keywords

  • glycosylation
  • M protein
  • pathogenesis
  • blood group antigens

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    De Oliveira, D. M. P., Everest-Dass, A., Hartley-Tassell, L., Day, C. J., Indraratna, A., Brouwer, S., ... Sanderson-Smith, M. L. (2019). Human glycan expression patterns influence Group A streptococcal colonization of epithelial cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 33(10), 10808-10818. https://doi.org/10.1096/fj.201900559R