Production and Composition of Group B Streptococcal Membrane Vesicles Vary Across Diverse Lineages

Although the neonatal and fetal pathogen Group B Streptococcus (GBS) asymptomatically colonizes the vaginal tract of ∼30% of pregnant women, only a fraction of their offspring develops invasive disease. We and others have postulated that these dimorphic clinical phenotypes are driven by strain varia...

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Main Authors: Cole R. McCutcheon, Macy E. Pell, Jennifer A. Gaddy, David M. Aronoff, Margaret G. Petroff, Shannon D. Manning
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-11-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2021.770499/full
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author Cole R. McCutcheon
Macy E. Pell
Jennifer A. Gaddy
Jennifer A. Gaddy
Jennifer A. Gaddy
David M. Aronoff
David M. Aronoff
David M. Aronoff
Margaret G. Petroff
Margaret G. Petroff
Shannon D. Manning
author_facet Cole R. McCutcheon
Macy E. Pell
Jennifer A. Gaddy
Jennifer A. Gaddy
Jennifer A. Gaddy
David M. Aronoff
David M. Aronoff
David M. Aronoff
Margaret G. Petroff
Margaret G. Petroff
Shannon D. Manning
author_sort Cole R. McCutcheon
collection DOAJ
description Although the neonatal and fetal pathogen Group B Streptococcus (GBS) asymptomatically colonizes the vaginal tract of ∼30% of pregnant women, only a fraction of their offspring develops invasive disease. We and others have postulated that these dimorphic clinical phenotypes are driven by strain variability; however, the bacterial factors that promote these divergent clinical phenotypes remain unclear. It was previously shown that GBS produces membrane vesicles (MVs) that contain active virulence factors capable of inducing adverse pregnancy outcomes. Because the relationship between strain variation and vesicle composition or production is unknown, we sought to quantify MV production and examine the protein composition, using label-free proteomics on MVs produced by diverse clinical GBS strains representing three phylogenetically distinct lineages. We found that MV production varied across strains, with certain strains displaying nearly twofold increases in production relative to others. Hierarchical clustering and principal component analysis of the proteomes revealed that MV composition is lineage-dependent but independent of clinical phenotype. Multiple proteins that contribute to virulence or immunomodulation, including hyaluronidase, C5a peptidase, and sialidases, were differentially abundant in MVs, and were partially responsible for this divergence. Together, these data indicate that production and composition of GBS MVs vary in a strain-dependent manner, suggesting that MVs have lineage-specific functions relating to virulence. Such differences may contribute to variation in clinical phenotypes observed among individuals infected with GBS strains representing distinct lineages.
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spelling doaj.art-526121ad7f7e4963ba344e04654c81812022-12-21T19:23:09ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-11-011210.3389/fmicb.2021.770499770499Production and Composition of Group B Streptococcal Membrane Vesicles Vary Across Diverse LineagesCole R. McCutcheon0Macy E. Pell1Jennifer A. Gaddy2Jennifer A. Gaddy3Jennifer A. Gaddy4David M. Aronoff5David M. Aronoff6David M. Aronoff7Margaret G. Petroff8Margaret G. Petroff9Shannon D. Manning10Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, United StatesDepartment of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, United StatesDivision of Infectious Disease, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United StatesDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, United StatesTennessee Valley Healthcare System, Department of Veterans Affairs, Nashville, TN, United StatesDivision of Infectious Disease, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United StatesDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, United StatesDepartment of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, TN, United StatesDepartment of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, United StatesDepartment of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI, United StatesDepartment of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, United StatesAlthough the neonatal and fetal pathogen Group B Streptococcus (GBS) asymptomatically colonizes the vaginal tract of ∼30% of pregnant women, only a fraction of their offspring develops invasive disease. We and others have postulated that these dimorphic clinical phenotypes are driven by strain variability; however, the bacterial factors that promote these divergent clinical phenotypes remain unclear. It was previously shown that GBS produces membrane vesicles (MVs) that contain active virulence factors capable of inducing adverse pregnancy outcomes. Because the relationship between strain variation and vesicle composition or production is unknown, we sought to quantify MV production and examine the protein composition, using label-free proteomics on MVs produced by diverse clinical GBS strains representing three phylogenetically distinct lineages. We found that MV production varied across strains, with certain strains displaying nearly twofold increases in production relative to others. Hierarchical clustering and principal component analysis of the proteomes revealed that MV composition is lineage-dependent but independent of clinical phenotype. Multiple proteins that contribute to virulence or immunomodulation, including hyaluronidase, C5a peptidase, and sialidases, were differentially abundant in MVs, and were partially responsible for this divergence. Together, these data indicate that production and composition of GBS MVs vary in a strain-dependent manner, suggesting that MVs have lineage-specific functions relating to virulence. Such differences may contribute to variation in clinical phenotypes observed among individuals infected with GBS strains representing distinct lineages.https://www.frontiersin.org/articles/10.3389/fmicb.2021.770499/fullStreptococcus agalactiaemembrane vesiclesvirulencepathogenesisproteomicsgroup B Streptococcus
spellingShingle Cole R. McCutcheon
Macy E. Pell
Jennifer A. Gaddy
Jennifer A. Gaddy
Jennifer A. Gaddy
David M. Aronoff
David M. Aronoff
David M. Aronoff
Margaret G. Petroff
Margaret G. Petroff
Shannon D. Manning
Production and Composition of Group B Streptococcal Membrane Vesicles Vary Across Diverse Lineages
Frontiers in Microbiology
Streptococcus agalactiae
membrane vesicles
virulence
pathogenesis
proteomics
group B Streptococcus
title Production and Composition of Group B Streptococcal Membrane Vesicles Vary Across Diverse Lineages
title_full Production and Composition of Group B Streptococcal Membrane Vesicles Vary Across Diverse Lineages
title_fullStr Production and Composition of Group B Streptococcal Membrane Vesicles Vary Across Diverse Lineages
title_full_unstemmed Production and Composition of Group B Streptococcal Membrane Vesicles Vary Across Diverse Lineages
title_short Production and Composition of Group B Streptococcal Membrane Vesicles Vary Across Diverse Lineages
title_sort production and composition of group b streptococcal membrane vesicles vary across diverse lineages
topic Streptococcus agalactiae
membrane vesicles
virulence
pathogenesis
proteomics
group B Streptococcus
url https://www.frontiersin.org/articles/10.3389/fmicb.2021.770499/full
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