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

Shi, Miaomiao; Willing, Stephanie E.; Kim, Hwan Keun; Schneewind, Olaf; Missiakas, Dominique

doi:10.1128/mBio.00039-21

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

Journal Article · Tue Apr 27 00:00:00 EDT 2021 · mBio (Online)

DOI:https://doi.org/10.1128/mBio.00039-21· OSTI ID:1815827

Shi, Miaomiao ^[1]; Willing, Stephanie E. ^[2]; Kim, Hwan Keun ^[2]; Schneewind, Olaf ^[2];

^[3]

Argonne National Lab. (ANL), Argonne, IL (United States). Howard Taylor Ricketts Lab.
Univ. of Chicago, IL (United States). Dept. of Microbiology
Argonne National Lab. (ANL), Argonne, IL (United States). Howard Taylor Ricketts Lab.; Univ. of Chicago, IL (United States). Dept. of Microbiology

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_H3) idiotype (IgM) B cell receptors, promoting B cell expansion and the secretion of nonspecific V_H3-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.

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Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1815827

Journal Information:: mBio (Online), Vol. 12, Issue 2; ISSN 2150-7511

Publisher:: American Society for Microbiology (ASM)Copyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
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Title: Peptidoglycan Contribution to the B Cell Superantigen Activity of Staphylococcal Protein A

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