Peptidoglycan Contribution to the B Cell Superantigen Activity of Staphylococcal Protein A

ABSTRACT 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) mol...

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Autores principales:	Miaomiao Shi, Stephanie E. Willing, Hwan Keun Kim, Olaf Schneewind, Dominique Missiakas
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	B cell receptor LysM protein A Staphylococcus aureus peptidoglycan superantigens Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9f372872ce4e488c95860d2f26c772c0
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spelling	oai:doaj.org-article:9f372872ce4e488c95860d2f26c772c02021-11-10T18:37:48ZPeptidoglycan Contribution to the B Cell Superantigen Activity of Staphylococcal Protein A10.1128/mBio.00039-212150-7511https://doaj.org/article/9f372872ce4e488c95860d2f26c772c02021-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00039-21https://doaj.org/toc/2150-7511ABSTRACT 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 (VH3) idiotype (IgM) B cell receptors, promoting B cell expansion and the secretion of nonspecific VH3-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. IMPORTANCE The LysM domain is found in all kingdoms of life. While their function in mammals is not known, LysM domains of bacteria and their phage parasites are associated with enzymes that cleave or remodel peptidoglycan. Plants recognize microbe-associated molecular patterns such as chitin via receptors endowed with LysM-containing ectodomains. In plants, such receptors play equally important roles in defense and symbiosis signaling. SpA of S. aureus carries a LysM domain that binds glycan strands of peptidoglycan to influence defined B cell responses that divert pathogen-specific adaptive immune responses.Miaomiao ShiStephanie E. WillingHwan Keun KimOlaf SchneewindDominique MissiakasAmerican Society for MicrobiologyarticleB cell receptorLysMprotein AStaphylococcus aureuspeptidoglycansuperantigensMicrobiologyQR1-502ENmBio, Vol 12, Iss 2 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	B cell receptor LysM protein A Staphylococcus aureus peptidoglycan superantigens Microbiology QR1-502
spellingShingle	B cell receptor LysM protein A Staphylococcus aureus peptidoglycan superantigens Microbiology QR1-502 Miaomiao Shi Stephanie E. Willing Hwan Keun Kim Olaf Schneewind Dominique Missiakas Peptidoglycan Contribution to the B Cell Superantigen Activity of Staphylococcal Protein A
description	ABSTRACT 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 (VH3) idiotype (IgM) B cell receptors, promoting B cell expansion and the secretion of nonspecific VH3-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. IMPORTANCE The LysM domain is found in all kingdoms of life. While their function in mammals is not known, LysM domains of bacteria and their phage parasites are associated with enzymes that cleave or remodel peptidoglycan. Plants recognize microbe-associated molecular patterns such as chitin via receptors endowed with LysM-containing ectodomains. In plants, such receptors play equally important roles in defense and symbiosis signaling. SpA of S. aureus carries a LysM domain that binds glycan strands of peptidoglycan to influence defined B cell responses that divert pathogen-specific adaptive immune responses.
format	article
author	Miaomiao Shi Stephanie E. Willing Hwan Keun Kim Olaf Schneewind Dominique Missiakas
author_facet	Miaomiao Shi Stephanie E. Willing Hwan Keun Kim Olaf Schneewind Dominique Missiakas
author_sort	Miaomiao Shi
title	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_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_sort	peptidoglycan contribution to the b cell superantigen activity of staphylococcal protein a
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/9f372872ce4e488c95860d2f26c772c0
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Peptidoglycan Contribution to the B Cell Superantigen Activity of Staphylococcal Protein A

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