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MBio. 2017 Jan 24;8(1). pii: e02237-16. doi: 10.1128/mBio.02237-16.

Blood Group Antigen Recognition via the Group A Streptococcal M Protein Mediates Host Colonization.

Author information

  • 1School of Biological Sciences and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, Australia.
  • 2Institute for Glycomics, Griffith University, Gold Coast, Australia.
  • 3Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, Australia.
  • 4Australian Infectious Diseases Research Centre and School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Australia.
  • 5Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
  • 6Centre for Immunity, Infection and Inflammation, University of California, San Diego, California, USA.
  • 7School of Biological Sciences and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, Australia martina@uow.edu.au.

Abstract

Streptococcus pyogenes (group A streptococcus [GAS]) is responsible for over 500,000 deaths worldwide each year. The highly virulent M1T1 GAS clone is one of the most frequently isolated serotypes from streptococcal pharyngitis and invasive disease. The oral epithelial tract is a niche highly abundant in glycosylated structures, particularly those of the ABO(H) blood group antigen family. Using a high-throughput approach, we determined that a strain representative of the globally disseminated M1T1 GAS clone 5448 interacts with numerous, structurally diverse glycans. Preeminent among GAS virulence factors is the surface-expressed M protein. M1 protein showed high affinity for several terminal galactose blood group antigen structures. Deletion mutagenesis shows that M1 protein mediates glycan binding via its B repeat domains. Association of M1T1 GAS with oral epithelial cells varied significantly as a result of phenotypic differences in blood group antigen expression, with significantly higher adherence to those cells expressing H antigen structures compared to cells expressing A, B, or AB antigen structures. These data suggest a novel mechanism for GAS attachment to host cells and propose a link between host blood group antigen expression and M1T1 GAS colonization.

IMPORTANCE:

There has been a resurgence in group A streptococcal (GAS) invasive disease, which has been paralleled by the emergence of the highly virulent M1T1 GAS clone. Intensive research has focused on mechanisms that contribute to the invasive nature of this serotype, while the mechanisms that contribute to host susceptibility to disease and bacterial colonization and persistence are still poorly understood. The M1T1 GAS clone is frequently isolated from the throat, an environment highly abundant in blood group antigen structures. This work examined the interaction of the M1 protein, the preeminent GAS surface protein, against a wide range of host-expressed glycan structures. Our data suggest that susceptibility to infection by GAS in the oral tract may correlate with phenotypic differences in host blood group antigen expression. Thus, variations in host blood group antigen expression may serve as a selective pressure contributing to the dissemination and overrepresentation of M1T1 GAS.

PMID:
28119471
PMCID:
PMC5263248
DOI:
10.1128/mBio.02237-16
[PubMed - in process]
Free PMC Article
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