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

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 high...

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Autores principales: David M. P. De Oliveira, Lauren Hartley-Tassell, Arun Everest-Dass, Christopher J. Day, Rebecca A. Dabbs, Thomas Ve, Bostjan Kobe, Victor Nizet, Nicolle H. Packer, Mark J. Walker, Michael P. Jennings, Martina L. Sanderson-Smith
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Publicado: American Society for Microbiology 2017
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spelling oai:doaj.org-article:a691605b870247b8b88dbc858307280f2021-11-15T15:51:07ZBlood Group Antigen Recognition via the Group A Streptococcal M Protein Mediates Host Colonization10.1128/mBio.02237-162150-7511https://doaj.org/article/a691605b870247b8b88dbc858307280f2017-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02237-16https://doaj.org/toc/2150-7511ABSTRACT 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.David M. P. De OliveiraLauren Hartley-TassellArun Everest-DassChristopher J. DayRebecca A. DabbsThomas VeBostjan KobeVictor NizetNicolle H. PackerMark J. WalkerMichael P. JenningsMartina L. Sanderson-SmithAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 8, Iss 1 (2017)
institution DOAJ
collection DOAJ
language EN
topic Microbiology
QR1-502
spellingShingle Microbiology
QR1-502
David M. P. De Oliveira
Lauren Hartley-Tassell
Arun Everest-Dass
Christopher J. Day
Rebecca A. Dabbs
Thomas Ve
Bostjan Kobe
Victor Nizet
Nicolle H. Packer
Mark J. Walker
Michael P. Jennings
Martina L. Sanderson-Smith
Blood Group Antigen Recognition via the Group A Streptococcal M Protein Mediates Host Colonization
description 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.
format article
author David M. P. De Oliveira
Lauren Hartley-Tassell
Arun Everest-Dass
Christopher J. Day
Rebecca A. Dabbs
Thomas Ve
Bostjan Kobe
Victor Nizet
Nicolle H. Packer
Mark J. Walker
Michael P. Jennings
Martina L. Sanderson-Smith
author_facet David M. P. De Oliveira
Lauren Hartley-Tassell
Arun Everest-Dass
Christopher J. Day
Rebecca A. Dabbs
Thomas Ve
Bostjan Kobe
Victor Nizet
Nicolle H. Packer
Mark J. Walker
Michael P. Jennings
Martina L. Sanderson-Smith
author_sort David M. P. De Oliveira
title Blood Group Antigen Recognition via the Group A Streptococcal M Protein Mediates Host Colonization
title_short Blood Group Antigen Recognition via the Group A Streptococcal M Protein Mediates Host Colonization
title_full Blood Group Antigen Recognition via the Group A Streptococcal M Protein Mediates Host Colonization
title_fullStr Blood Group Antigen Recognition via the Group A Streptococcal M Protein Mediates Host Colonization
title_full_unstemmed Blood Group Antigen Recognition via the Group A Streptococcal M Protein Mediates Host Colonization
title_sort blood group antigen recognition via the group a streptococcal m protein mediates host colonization
publisher American Society for Microbiology
publishDate 2017
url https://doaj.org/article/a691605b870247b8b88dbc858307280f
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