A Novel Conserved Protein in Streptococcus agalactiae, BvaP, Is Important for Vaginal Colonization and Biofilm Formation

ABSTRACT Streptococcus agalactiae (group B streptococcus [GBS]) infections in neonates are often fatal and strongly associated with maternal GBS vaginal colonization. Here, we investigated the role of an uncharacterized protein, BvaP, in GBS vaginal colonization. bvaP was previously identified as th...

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Main Authors: Lamar S. Thomas, Laura C. Cook
Format: Article
Language:English
Published: American Society for Microbiology 2022-12-01
Series:mSphere
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/msphere.00421-22
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author Lamar S. Thomas
Laura C. Cook
author_facet Lamar S. Thomas
Laura C. Cook
author_sort Lamar S. Thomas
collection DOAJ
description ABSTRACT Streptococcus agalactiae (group B streptococcus [GBS]) infections in neonates are often fatal and strongly associated with maternal GBS vaginal colonization. Here, we investigated the role of an uncharacterized protein, BvaP, in GBS vaginal colonization. bvaP was previously identified as the most highly upregulated gene in the GBS A909 transcriptome when comparing vaginal colonization to growth in liquid culture. We found that the absence of BvaP affects the ability of GBS to adhere to extracellular matrix components and human vaginal epithelial cells, and the ability of a ΔbvaP mutant to colonize the murine vaginal tract was significantly decreased. Cellular morphological alterations such as changes in cell shape, chain length, and clumping were also observed in a knockout mutant strain. Given its high expression level in vivo, high degree of conservation among GBS strains, and role in vaginal colonization, BvaP may be an eligible target for GBS vaccination and/or drug therapy. IMPORTANCE Neonatal GBS disease is a major cause of morbidity and mortality, and maternal vaginal colonization is the leading risk factor for the disease. Colonization prevention would greatly impact the rates of disease transmission, but vaccine development has stalled as capsular polysaccharide vaccines have low immunogenicity in vivo. While these vaccines are still in development, the addition of a protein conjugate may prove fruitful in increasing immunogenicity and strain coverage across GBS serotypes. Previous research identified sak_1753 as a highly upregulated gene during murine vaginal colonization. This study reveals that Sak_1753 is required to maintain proper GBS cellular morphology and colonization phenotypes and is required for full in vivo vaginal colonization in a murine model. We have renamed Sak_1753 group B streptococcus vaginal adherence protein (BvaP). The findings of this study indicate that BvaP is important for GBS colonization of the vaginal tract and, given its high expression level in vivo and strain conservation, may be a candidate for vaccine development.
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spelling doaj.art-5913b7606fd7410db1b918a4fafe1d852022-12-22T03:55:21ZengAmerican Society for MicrobiologymSphere2379-50422022-12-017610.1128/msphere.00421-22A Novel Conserved Protein in Streptococcus agalactiae, BvaP, Is Important for Vaginal Colonization and Biofilm FormationLamar S. Thomas0Laura C. Cook1Binghamton Biofilm Research Center, Department of Biology, Binghamton University, Binghamton, New York, USABinghamton Biofilm Research Center, Department of Biology, Binghamton University, Binghamton, New York, USAABSTRACT Streptococcus agalactiae (group B streptococcus [GBS]) infections in neonates are often fatal and strongly associated with maternal GBS vaginal colonization. Here, we investigated the role of an uncharacterized protein, BvaP, in GBS vaginal colonization. bvaP was previously identified as the most highly upregulated gene in the GBS A909 transcriptome when comparing vaginal colonization to growth in liquid culture. We found that the absence of BvaP affects the ability of GBS to adhere to extracellular matrix components and human vaginal epithelial cells, and the ability of a ΔbvaP mutant to colonize the murine vaginal tract was significantly decreased. Cellular morphological alterations such as changes in cell shape, chain length, and clumping were also observed in a knockout mutant strain. Given its high expression level in vivo, high degree of conservation among GBS strains, and role in vaginal colonization, BvaP may be an eligible target for GBS vaccination and/or drug therapy. IMPORTANCE Neonatal GBS disease is a major cause of morbidity and mortality, and maternal vaginal colonization is the leading risk factor for the disease. Colonization prevention would greatly impact the rates of disease transmission, but vaccine development has stalled as capsular polysaccharide vaccines have low immunogenicity in vivo. While these vaccines are still in development, the addition of a protein conjugate may prove fruitful in increasing immunogenicity and strain coverage across GBS serotypes. Previous research identified sak_1753 as a highly upregulated gene during murine vaginal colonization. This study reveals that Sak_1753 is required to maintain proper GBS cellular morphology and colonization phenotypes and is required for full in vivo vaginal colonization in a murine model. We have renamed Sak_1753 group B streptococcus vaginal adherence protein (BvaP). The findings of this study indicate that BvaP is important for GBS colonization of the vaginal tract and, given its high expression level in vivo and strain conservation, may be a candidate for vaccine development.https://journals.asm.org/doi/10.1128/msphere.00421-22adherencecolonizationstreptococcusvaginal
spellingShingle Lamar S. Thomas
Laura C. Cook
A Novel Conserved Protein in Streptococcus agalactiae, BvaP, Is Important for Vaginal Colonization and Biofilm Formation
mSphere
adherence
colonization
streptococcus
vaginal
title A Novel Conserved Protein in Streptococcus agalactiae, BvaP, Is Important for Vaginal Colonization and Biofilm Formation
title_full A Novel Conserved Protein in Streptococcus agalactiae, BvaP, Is Important for Vaginal Colonization and Biofilm Formation
title_fullStr A Novel Conserved Protein in Streptococcus agalactiae, BvaP, Is Important for Vaginal Colonization and Biofilm Formation
title_full_unstemmed A Novel Conserved Protein in Streptococcus agalactiae, BvaP, Is Important for Vaginal Colonization and Biofilm Formation
title_short A Novel Conserved Protein in Streptococcus agalactiae, BvaP, Is Important for Vaginal Colonization and Biofilm Formation
title_sort novel conserved protein in streptococcus agalactiae bvap is important for vaginal colonization and biofilm formation
topic adherence
colonization
streptococcus
vaginal
url https://journals.asm.org/doi/10.1128/msphere.00421-22
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