Characterization of a two component regulatory system in Group B Streptococcus

Project Summary Streptococcus agalactiae (Group B Strep, GBS) infections in neonates are often fatal and are strongly associated with maternal GBS vaginal colonization. Current treatment strategies involve preventing vertical transmission and infection of neonates via intrapartum antibiotics. As this treatment presents an array of negative effects including altering the neonatal gut microbiota and increased use of antibiotics clinically, a strategy to prevent maternal vaginal colonization would be highly preferable. Our data show that the GBS genes pbsP, encoding a streptococcal adhesin important for colonization and systemic infection, and sak_1753 (bvaP), encoding a hypothetical protein, are regulated by a two-component signal transduction system, SaeRS. In GBS, SaeRS is activated by signals present in the murine vaginal tract to directly up-regulate expression of both of these genes. bvaP is the most highly upregulated gene in vivo compared to liquid culture and recently published data shows that BvaP plays an important role in host colonization and GBS cellular morphology. The goals of this proposal are to (1) characterize environmental sensing and signal transduction by the two-component system SaeRS including the activating host signals and the downstream regulatory networks controlled by this system, (2) characterize the BvaP protein and the role of its conserved repeat domains and protein localization in phenotypes associated with host colonization.