Production and composition of group B streptococcal membrane vesicles varies across diverse lineages

Abstract

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 two-fold 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.

Mechanisms of group B Streptococcus-mediated preterm birth: lessons learnt from animal models

“…An interesting phenomenon uncovered while exploration of the mechanism of GBS infection was the finding of MV of GBS ( Surve et al 2016 , Kurian & Modi 2019 , Mehanny et al 2020 , Armistead et al 2021 , McCutcheon et al 2021 ). There exists experimental evidence to show that the MVs can induce preterm birth and fetal injury when administered prenatally ( Surve et al 2016 ) and aggravate morbidity and mortality of mice infected with GBS when administrated neonatally ( Armistead et al 2021 ).…”

“…There exists experimental evidence to show that the MVs can induce preterm birth and fetal injury when administered prenatally ( Surve et al 2016 ) and aggravate morbidity and mortality of mice infected with GBS when administrated neonatally ( Armistead et al 2021 ). GBS MVs are nearly 50–300 nm in diameter and filled with virulence factors ( Surve et al 2016 , McCutcheon et al 2021 ). The GBS MVs can internalize in a range of cell lines including HeLa ( Surve et al 2016 ), human lung epithelial cell line (A549), human keratinocyte cell line (HaCaT), differentiated macrophage-like cells (dTHP-1), and murine dendritic DC2.4 ( Mehanny et al 2020 ).…”

“…The GBS MVs are enriched with nucleic acids, certain lipids, and virulent factors including hyaluronate lyases, C5a peptidase, and sialidases ( Surve et al 2016 , McCutcheon et al 2021 ). There appears to be some strain-specific differences in the components of GBS MVs ( Bohnsack et al .…”

“…1993 , Chang et al . 2014 ) where only 62/643 MV proteins are common to six strains of GBS ( McCutcheon et al 2021 ) and these proteins can be the signature of the GBS MV proteome.…”