Cargando…
Peptidoglycan Contribution to the B Cell Superantigen Activity of Staphylococcal Protein A
Staphylococcus aureus causes reiterative and chronic persistent infections. This can be explained by the formidable ability of this pathogen to escape immune surveillance mechanisms. Cells of S. aureus display the abundant staphylococcal protein A (SpA). SpA binds to immunoglobulin (Ig) molecules an...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092194/ https://www.ncbi.nlm.nih.gov/pubmed/33879590 http://dx.doi.org/10.1128/mBio.00039-21 |
_version_ | 1783687608241487872 |
---|---|
author | Shi, Miaomiao Willing, Stephanie E. Kim, Hwan Keun Schneewind, Olaf Missiakas, Dominique |
author_facet | Shi, Miaomiao Willing, Stephanie E. Kim, Hwan Keun Schneewind, Olaf Missiakas, Dominique |
author_sort | Shi, Miaomiao |
collection | PubMed |
description | Staphylococcus aureus causes reiterative and chronic persistent infections. This can be explained by the formidable ability of this pathogen to escape immune surveillance mechanisms. Cells of S. aureus display the abundant staphylococcal protein A (SpA). SpA binds to immunoglobulin (Ig) molecules and coats the bacterial surface to prevent phagocytic uptake. SpA also binds and cross-links variable heavy 3 (V(H)3) idiotype (IgM) B cell receptors, promoting B cell expansion and the secretion of nonspecific V(H)3-IgM via a mechanism requiring CD4(+) T cell help. SpA binding to antibodies is mediated by the N-terminal Ig-binding domains (IgBDs). The so-called region X, uncharacterized LysM domain, and C-terminal LPXTG sorting signal for peptidoglycan attachment complete the linear structure of the protein. Here, we report that both the LysM domain and the LPXTG motif sorting signal are required for the B cell superantigen activity of SpA in a mouse model of infection. SpA molecules purified from staphylococcal cultures are sufficient to exert B cell superantigen activity and promote immunoglobulin secretion as long as they carry intact LysM and LPXTG motif domains with bound peptidoglycan fragments. The LysM domain binds the glycan chains of peptidoglycan fragments, whereas the LPXTG motif is covalently linked to wall peptides lacking glycan. These findings emphasize the complexity of SpA interactions with B cell receptors. |
format | Online Article Text |
id | pubmed-8092194 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-80921942021-05-04 Peptidoglycan Contribution to the B Cell Superantigen Activity of Staphylococcal Protein A Shi, Miaomiao Willing, Stephanie E. Kim, Hwan Keun Schneewind, Olaf Missiakas, Dominique mBio Research Article Staphylococcus aureus causes reiterative and chronic persistent infections. This can be explained by the formidable ability of this pathogen to escape immune surveillance mechanisms. Cells of S. aureus display the abundant staphylococcal protein A (SpA). SpA binds to immunoglobulin (Ig) molecules and coats the bacterial surface to prevent phagocytic uptake. SpA also binds and cross-links variable heavy 3 (V(H)3) idiotype (IgM) B cell receptors, promoting B cell expansion and the secretion of nonspecific V(H)3-IgM via a mechanism requiring CD4(+) T cell help. SpA binding to antibodies is mediated by the N-terminal Ig-binding domains (IgBDs). The so-called region X, uncharacterized LysM domain, and C-terminal LPXTG sorting signal for peptidoglycan attachment complete the linear structure of the protein. Here, we report that both the LysM domain and the LPXTG motif sorting signal are required for the B cell superantigen activity of SpA in a mouse model of infection. SpA molecules purified from staphylococcal cultures are sufficient to exert B cell superantigen activity and promote immunoglobulin secretion as long as they carry intact LysM and LPXTG motif domains with bound peptidoglycan fragments. The LysM domain binds the glycan chains of peptidoglycan fragments, whereas the LPXTG motif is covalently linked to wall peptides lacking glycan. These findings emphasize the complexity of SpA interactions with B cell receptors. American Society for Microbiology 2021-04-20 /pmc/articles/PMC8092194/ /pubmed/33879590 http://dx.doi.org/10.1128/mBio.00039-21 Text en Copyright © 2021 Shi et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Shi, Miaomiao Willing, Stephanie E. Kim, Hwan Keun Schneewind, Olaf Missiakas, Dominique Peptidoglycan Contribution to the B Cell Superantigen Activity of Staphylococcal Protein A |
title | Peptidoglycan Contribution to the B Cell Superantigen Activity of Staphylococcal Protein A |
title_full | Peptidoglycan Contribution to the B Cell Superantigen Activity of Staphylococcal Protein A |
title_fullStr | Peptidoglycan Contribution to the B Cell Superantigen Activity of Staphylococcal Protein A |
title_full_unstemmed | Peptidoglycan Contribution to the B Cell Superantigen Activity of Staphylococcal Protein A |
title_short | Peptidoglycan Contribution to the B Cell Superantigen Activity of Staphylococcal Protein A |
title_sort | peptidoglycan contribution to the b cell superantigen activity of staphylococcal protein a |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092194/ https://www.ncbi.nlm.nih.gov/pubmed/33879590 http://dx.doi.org/10.1128/mBio.00039-21 |
work_keys_str_mv | AT shimiaomiao peptidoglycancontributiontothebcellsuperantigenactivityofstaphylococcalproteina AT willingstephaniee peptidoglycancontributiontothebcellsuperantigenactivityofstaphylococcalproteina AT kimhwankeun peptidoglycancontributiontothebcellsuperantigenactivityofstaphylococcalproteina AT schneewindolaf peptidoglycancontributiontothebcellsuperantigenactivityofstaphylococcalproteina AT missiakasdominique peptidoglycancontributiontothebcellsuperantigenactivityofstaphylococcalproteina |