Virulence Role of the GlcNAc Side Chain of the Lancefield Cell Wall Carbohydrate Antigen in Non-M1-Serotype Group A <italic toggle="yes">Streptococcus</italic>

ABSTRACT Classification of streptococci is based upon expression of unique cell wall carbohydrate antigens. All serotypes of group A Streptococcus (GAS; Streptococcus pyogenes), a leading cause of infection-related mortality worldwide, express the group A carbohydrate (GAC). GAC, the classical Lance...

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Autores principales:	Anna Henningham, Mark R. Davies, Satoshi Uchiyama, Nina M. van Sorge, Sean Lund, Kelsey T. Chen, Mark J. Walker, Jason N. Cole, Victor Nizet
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	group A carbohydrate group A Streptococcus Lancefield antigen Streptococcus pyogenes virulence factor innate immunity Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2a9124934a954b3e8c349449b28ec1db
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spelling	oai:doaj.org-article:2a9124934a954b3e8c349449b28ec1db2021-11-15T15:53:26ZVirulence Role of the GlcNAc Side Chain of the Lancefield Cell Wall Carbohydrate Antigen in Non-M1-Serotype Group A <italic toggle="yes">Streptococcus</italic>10.1128/mBio.02294-172150-7511https://doaj.org/article/2a9124934a954b3e8c349449b28ec1db2018-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02294-17https://doaj.org/toc/2150-7511ABSTRACT Classification of streptococci is based upon expression of unique cell wall carbohydrate antigens. All serotypes of group A Streptococcus (GAS; Streptococcus pyogenes), a leading cause of infection-related mortality worldwide, express the group A carbohydrate (GAC). GAC, the classical Lancefield antigen, is comprised of a polyrhamnose backbone with N-acetylglucosamine (GlcNAc) side chains. The immunodominant GlcNAc epitope of GAC is the basis of all rapid diagnostic testing for GAS infection. We previously identified the 12-gene GAC biosynthesis gene cluster and determined that the glycosyltransferase GacI was required for addition of the GlcNAc side chain to the polyrhamnose core. Loss of the GAC GlcNAc epitope in serotype M1 GAS resulted in attenuated virulence in two animal infection models and increased GAS sensitivity to killing by whole human blood, serum, neutrophils, and antimicrobial peptides. Here, we report that the GAC biosynthesis gene cluster is ubiquitous among 520 GAS isolates from global sources, representing 105 GAS emm serotypes. Isogenic ΔgacI mutants were constructed in M2, M3, M4, M28, and M89 backgrounds and displayed an array of phenotypes in susceptibility to killing by whole human blood, baby rabbit serum, human platelet releasate, human neutrophils, and antimicrobial peptide LL-37. The contribution of the GlcNAc side chain to GAS survival in vivo also varied by strain, demonstrating that it is not a prerequisite for virulence in the murine infection model. Thus, the relative contribution of GAC to virulence in non-M1 serotypes appears to depend on the quorum of other virulence factors that each strain possesses. IMPORTANCE The Lancefield group A carbohydrate (GAC) is the species-defining antigen for group A Streptococcus (GAS), comprising ~50% of the cell wall of this major human pathogen. We previously showed that the GlcNAc side chain of GAC contributes to the innate immune resistance and animal virulence phenotypes of the globally disseminated strain of serotype M1 GAS. Here, we use isogenic mutagenesis to examine the role of GAC GlcNAc in five additional medically relevant GAS serotypes. Overall, the GlcNAc side chain of GAC contributes to the innate immune resistance of GAS, but the relative contribution varies among individual strains. Moreover, the GAC GlcNAc side chain is not a universal prerequisite for GAS virulence in the animal model.Anna HenninghamMark R. DaviesSatoshi UchiyamaNina M. van SorgeSean LundKelsey T. ChenMark J. WalkerJason N. ColeVictor NizetAmerican Society for Microbiologyarticlegroup A carbohydrategroup A StreptococcusLancefield antigenStreptococcus pyogenesvirulence factorinnate immunityMicrobiologyQR1-502ENmBio, Vol 9, Iss 1 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	group A carbohydrate group A Streptococcus Lancefield antigen Streptococcus pyogenes virulence factor innate immunity Microbiology QR1-502
spellingShingle	group A carbohydrate group A Streptococcus Lancefield antigen Streptococcus pyogenes virulence factor innate immunity Microbiology QR1-502 Anna Henningham Mark R. Davies Satoshi Uchiyama Nina M. van Sorge Sean Lund Kelsey T. Chen Mark J. Walker Jason N. Cole Victor Nizet Virulence Role of the GlcNAc Side Chain of the Lancefield Cell Wall Carbohydrate Antigen in Non-M1-Serotype Group A <italic toggle="yes">Streptococcus</italic>
description	ABSTRACT Classification of streptococci is based upon expression of unique cell wall carbohydrate antigens. All serotypes of group A Streptococcus (GAS; Streptococcus pyogenes), a leading cause of infection-related mortality worldwide, express the group A carbohydrate (GAC). GAC, the classical Lancefield antigen, is comprised of a polyrhamnose backbone with N-acetylglucosamine (GlcNAc) side chains. The immunodominant GlcNAc epitope of GAC is the basis of all rapid diagnostic testing for GAS infection. We previously identified the 12-gene GAC biosynthesis gene cluster and determined that the glycosyltransferase GacI was required for addition of the GlcNAc side chain to the polyrhamnose core. Loss of the GAC GlcNAc epitope in serotype M1 GAS resulted in attenuated virulence in two animal infection models and increased GAS sensitivity to killing by whole human blood, serum, neutrophils, and antimicrobial peptides. Here, we report that the GAC biosynthesis gene cluster is ubiquitous among 520 GAS isolates from global sources, representing 105 GAS emm serotypes. Isogenic ΔgacI mutants were constructed in M2, M3, M4, M28, and M89 backgrounds and displayed an array of phenotypes in susceptibility to killing by whole human blood, baby rabbit serum, human platelet releasate, human neutrophils, and antimicrobial peptide LL-37. The contribution of the GlcNAc side chain to GAS survival in vivo also varied by strain, demonstrating that it is not a prerequisite for virulence in the murine infection model. Thus, the relative contribution of GAC to virulence in non-M1 serotypes appears to depend on the quorum of other virulence factors that each strain possesses. IMPORTANCE The Lancefield group A carbohydrate (GAC) is the species-defining antigen for group A Streptococcus (GAS), comprising ~50% of the cell wall of this major human pathogen. We previously showed that the GlcNAc side chain of GAC contributes to the innate immune resistance and animal virulence phenotypes of the globally disseminated strain of serotype M1 GAS. Here, we use isogenic mutagenesis to examine the role of GAC GlcNAc in five additional medically relevant GAS serotypes. Overall, the GlcNAc side chain of GAC contributes to the innate immune resistance of GAS, but the relative contribution varies among individual strains. Moreover, the GAC GlcNAc side chain is not a universal prerequisite for GAS virulence in the animal model.
format	article
author	Anna Henningham Mark R. Davies Satoshi Uchiyama Nina M. van Sorge Sean Lund Kelsey T. Chen Mark J. Walker Jason N. Cole Victor Nizet
author_facet	Anna Henningham Mark R. Davies Satoshi Uchiyama Nina M. van Sorge Sean Lund Kelsey T. Chen Mark J. Walker Jason N. Cole Victor Nizet
author_sort	Anna Henningham
title	Virulence Role of the GlcNAc Side Chain of the Lancefield Cell Wall Carbohydrate Antigen in Non-M1-Serotype Group A <italic toggle="yes">Streptococcus</italic>
title_short	Virulence Role of the GlcNAc Side Chain of the Lancefield Cell Wall Carbohydrate Antigen in Non-M1-Serotype Group A <italic toggle="yes">Streptococcus</italic>
title_full	Virulence Role of the GlcNAc Side Chain of the Lancefield Cell Wall Carbohydrate Antigen in Non-M1-Serotype Group A <italic toggle="yes">Streptococcus</italic>
title_fullStr	Virulence Role of the GlcNAc Side Chain of the Lancefield Cell Wall Carbohydrate Antigen in Non-M1-Serotype Group A <italic toggle="yes">Streptococcus</italic>
title_full_unstemmed	Virulence Role of the GlcNAc Side Chain of the Lancefield Cell Wall Carbohydrate Antigen in Non-M1-Serotype Group A <italic toggle="yes">Streptococcus</italic>
title_sort	virulence role of the glcnac side chain of the lancefield cell wall carbohydrate antigen in non-m1-serotype group a <italic toggle="yes">streptococcus</italic>
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/2a9124934a954b3e8c349449b28ec1db
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Virulence Role of the GlcNAc Side Chain of the Lancefield Cell Wall Carbohydrate Antigen in Non-M1-Serotype Group A <italic toggle="yes">Streptococcus</italic>

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