A Vaginal Tract Signal Detected by the Group B Streptococcus SaeRS System Elicits Transcriptomic Changes and Enhances Murine Colonization

Abstract

(group B streptococcus [GBS]) can colonize the human vaginal tract, leading to both superficial and serious infections in adults and neonates. To study bacterial colonization of the reproductive tract in a mammalian system, we employed a murine vaginal carriage model. Using transcriptome sequencing (RNA-Seq), the transcriptome of GBS growing during vaginal carriage was determined. Over one-quarter of the genes in GBS were found to be differentially regulated during colonization compared to laboratory cultures. A two-component system (TCS) homologous to the staphylococcal virulence regulator SaeRS was identified as being upregulated One of the SaeRS targets,, a proposed GBS vaccine candidate, is shown to be important for colonization of the vaginal tract. A component of vaginal lavage fluid acts as a signal to turn on expression via SaeRS. These data demonstrate the ability to quantify RNA expression directly from the murine vaginal tract and identify novel genes involved in vaginal colonization by GBS. They also provide more information about the regulation of an important virulence and colonization factor of GBS,, by the TCS SaeRS.

Identification of Zinc-Dependent Mechanisms Used by Group B Streptococcus To Overcome Calprotectin-Mediated Stress

“…Additionally, mntH encodes the manganese/iron NRAMP and is known to be important for survival under acidic conditions similar to what GBS would encounter during inflammation or within the phagolysosome (57). Similar to what has been shown for zinc import, the mtsABC transporter was shown to be upregulated in human blood and during vaginal colonization (76,77). In the context of metal ion efflux, we identified mutations in sczA, czcD, and cadD, which all resulted in fitness defects when grown in media containing calprotectin.…”

Identification of zinc-dependent mechanisms used by Group B Streptococcus to overcome calprotectin-mediated stress

“…Additionally, mntH, encodes the manganese/iron NRAMP and is known to be important for survival in acidic conditions similar to what GBS would encounter during inflammation or within the phagolysosome (55). Similar to what has been shown for zinc import, the mtsABC transporter was shown to be upregulated in human blood and during vaginal colonization (71,72). In the context of metal ion efflux, we identified mutations in sczA, czcD, and cadD, which all resulted in fitness defects when grown in media containing calprotectin.…”

“…AdcR is involved in maintaining intracellular zinc homeostasis, and has been shown to be important for growth in zinc-limiting conditions (38,39). This system is also significantly upregulated during GBS murine vaginal colonization and following incubation with human blood (71,72). In addition to the ABC transporters, bacteria have evolved other mechanisms to maintain zinc homeostasis, examples include the metallophore staphylopine produced by Staphylococcus aureus that binds zinc ions and is imported by the CntABCDF machinery (65), and the TdfH transporter of Neisseria gonorrhoeae that binds calprotectin directly to hijack and secure zinc ions (73).…”

The Streptococcus agalactiae cell wall‐anchored protein PbsP mediates adhesion to and invasion of epithelial cells by exploiting the host vitronectin/αv integrin axis

“…The PbsP adhesinis conserved in GBS strains belong to different clonal complexes. Its expression was recently demonstrated to be regulated at the transcriptional level by the SaeRS two‐component system in a murine model in which PbsP is necessary for vaginal colonization (Cook et al, ). In conclusion, PbsP is a multi‐ligand adhesion playing important roles in different steps of the pathogenesis of GBS disease.…”

“…For example, in a study which analyzed changes in the bacterial transcriptome induced by contact with human blood, none of the known or suspected virulence factors of GBS were strongly upregulated, with the exception of pbsP and a few other genes involved in plasminogen binding (Mereghetti et al, 2008). Similarly, transcriptomic analysis in a murine model of vaginal colonization indicated that pbsP was among the 10 most highly upregulated GBS genes in vivo (Cook et al, 2018). Gene deletion experiments also evidenced that pbsP was required for colonization of the murine vaginal tract, although the mechanisms involved were not investigated.…”