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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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2018-03-01
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| Series: | mBio |
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| Online Access: | https://journals.asm.org/doi/10.1128/mBio.02294-17 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T16:38:33Z |
| format | Article |
| id | doaj.art-2a9124934a954b3e8c349449b28ec1db |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-14T16:38:33Z |
| publishDate | 2018-03-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-2a9124934a954b3e8c349449b28ec1db2022-12-21T22:54:22ZengAmerican Society for MicrobiologymBio2150-75112018-03-019110.1128/mBio.02294-17Virulence Role of the GlcNAc Side Chain of the Lancefield Cell Wall Carbohydrate Antigen in Non-M1-Serotype Group A <italic toggle="yes">Streptococcus</italic>Anna Henningham0Mark R. Davies1Satoshi Uchiyama2Nina M. van Sorge3Sean Lund4Kelsey T. Chen5Mark J. Walker6Jason N. Cole7Victor Nizet8Department of Pediatrics, University of California, San Diego, California, USASchool of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, Queensland, AustraliaDepartment of Pediatrics, University of California, San Diego, California, USAMedical Microbiology, University Medical Center Utrecht, Utrecht, The NetherlandsDepartment of Pediatrics, University of California, San Diego, California, USADepartment of Pediatrics, University of California, San Diego, California, USASchool of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, Queensland, AustraliaDepartment of Pediatrics, University of California, San Diego, California, USADepartment of Pediatrics, University of California, San Diego, California, USAABSTRACT 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.https://journals.asm.org/doi/10.1128/mBio.02294-17group A carbohydrategroup A StreptococcusLancefield antigenStreptococcus pyogenesvirulence factorinnate immunity |
| spellingShingle | 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> mBio group A carbohydrate group A Streptococcus Lancefield antigen Streptococcus pyogenes virulence factor innate immunity |
| 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_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_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_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 |
| topic | group A carbohydrate group A Streptococcus Lancefield antigen Streptococcus pyogenes virulence factor innate immunity |
| url | https://journals.asm.org/doi/10.1128/mBio.02294-17 |
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