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The S Protein of Group B Streptococcus Is a Critical Virulence Determinant That Impacts the Cell Surface Virulome

Group B Streptococcus (GBS, S. agalactiae) is a human commensal and occasional pathogen that remains a leading cause of neonatal sepsis and meningitis with increasing disease burden in adult populations. Although programs for universal screening in pregnancy to guide intrapartum prophylaxis have red...

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Autores principales: Campeau, Anaamika, Uchiyama, Satoshi, Sanchez, Concepcion, Sauceda, Consuelo, Nizet, Victor, Gonzalez, David J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551713/
https://www.ncbi.nlm.nih.gov/pubmed/34721327
http://dx.doi.org/10.3389/fmicb.2021.729308
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author Campeau, Anaamika
Uchiyama, Satoshi
Sanchez, Concepcion
Sauceda, Consuelo
Nizet, Victor
Gonzalez, David J.
author_facet Campeau, Anaamika
Uchiyama, Satoshi
Sanchez, Concepcion
Sauceda, Consuelo
Nizet, Victor
Gonzalez, David J.
author_sort Campeau, Anaamika
collection PubMed
description Group B Streptococcus (GBS, S. agalactiae) is a human commensal and occasional pathogen that remains a leading cause of neonatal sepsis and meningitis with increasing disease burden in adult populations. Although programs for universal screening in pregnancy to guide intrapartum prophylaxis have reduced GBS invasive disease burden resulting from mother-to-newborn transfer during birth, better knowledge of disease mechanisms may elucidate new strategies to reduce antibiotic exposure. In our efforts to expand the knowledge base required for targeted anti-virulence therapies, we identified a GBS homolog for a recently identified virulence determinant of group A Streptococcus, S protein, and evaluated its role in GBS pathogenesis. A GBS S protein deletion mutant, Δess, showed altered cell-surface properties compared to the WT parent strain, including defective retention of its surface polysaccharide. Quantitative proteome analysis of enzymatically shaved surface epitopes of the GBS Δess mutant revealed a dysregulated cell surface virulome, with reduced abundance of several protein and glycoprotein components. The Δess mutant showed markedly attenuated virulence in a murine model of GBS systemic infection, with increased proteasome activity detected in the spleens of animals infected with the Δess mutant. These results expand the key roles S protein plays in streptococcal pathogenesis and introduces a new GBS virulence determinant and potential target for therapy development.
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spelling pubmed-85517132021-10-29 The S Protein of Group B Streptococcus Is a Critical Virulence Determinant That Impacts the Cell Surface Virulome Campeau, Anaamika Uchiyama, Satoshi Sanchez, Concepcion Sauceda, Consuelo Nizet, Victor Gonzalez, David J. Front Microbiol Microbiology Group B Streptococcus (GBS, S. agalactiae) is a human commensal and occasional pathogen that remains a leading cause of neonatal sepsis and meningitis with increasing disease burden in adult populations. Although programs for universal screening in pregnancy to guide intrapartum prophylaxis have reduced GBS invasive disease burden resulting from mother-to-newborn transfer during birth, better knowledge of disease mechanisms may elucidate new strategies to reduce antibiotic exposure. In our efforts to expand the knowledge base required for targeted anti-virulence therapies, we identified a GBS homolog for a recently identified virulence determinant of group A Streptococcus, S protein, and evaluated its role in GBS pathogenesis. A GBS S protein deletion mutant, Δess, showed altered cell-surface properties compared to the WT parent strain, including defective retention of its surface polysaccharide. Quantitative proteome analysis of enzymatically shaved surface epitopes of the GBS Δess mutant revealed a dysregulated cell surface virulome, with reduced abundance of several protein and glycoprotein components. The Δess mutant showed markedly attenuated virulence in a murine model of GBS systemic infection, with increased proteasome activity detected in the spleens of animals infected with the Δess mutant. These results expand the key roles S protein plays in streptococcal pathogenesis and introduces a new GBS virulence determinant and potential target for therapy development. Frontiers Media S.A. 2021-10-14 /pmc/articles/PMC8551713/ /pubmed/34721327 http://dx.doi.org/10.3389/fmicb.2021.729308 Text en Copyright © 2021 Campeau, Uchiyama, Sanchez, Sauceda, Nizet and Gonzalez. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Campeau, Anaamika
Uchiyama, Satoshi
Sanchez, Concepcion
Sauceda, Consuelo
Nizet, Victor
Gonzalez, David J.
The S Protein of Group B Streptococcus Is a Critical Virulence Determinant That Impacts the Cell Surface Virulome
title The S Protein of Group B Streptococcus Is a Critical Virulence Determinant That Impacts the Cell Surface Virulome
title_full The S Protein of Group B Streptococcus Is a Critical Virulence Determinant That Impacts the Cell Surface Virulome
title_fullStr The S Protein of Group B Streptococcus Is a Critical Virulence Determinant That Impacts the Cell Surface Virulome
title_full_unstemmed The S Protein of Group B Streptococcus Is a Critical Virulence Determinant That Impacts the Cell Surface Virulome
title_short The S Protein of Group B Streptococcus Is a Critical Virulence Determinant That Impacts the Cell Surface Virulome
title_sort s protein of group b streptococcus is a critical virulence determinant that impacts the cell surface virulome
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551713/
https://www.ncbi.nlm.nih.gov/pubmed/34721327
http://dx.doi.org/10.3389/fmicb.2021.729308
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