A novel conserved protein in Streptococcus agalactiae, BvaP, is important for vaginal colonization and biofilm formation

Abstract

Streptococcus agalactiae (Group B Strep, GBS) infections in neonates are often fatal and strongly associated with maternal GBS vaginal colonization. Here, we investigated the role of a previously 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 expression of BvaP affects GBS adherence to extracellular matrix components and human vaginal epithelial cells and a{Delta} bvaP mutant was significantly decreased in its ability to colonize the murine vaginal tract. 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 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. IMPORTANCENeonatal GBS disease is a major cause of morbidity and mortality and maternal vaginal colonization is the leading risk factor for disease. Colonization prevention would greatly impact 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, addition of a protein conjugate may prove fruitful in increasing immunogenicity and strain coverage across GBS serotypes. Previous research identified sak_1753 as a gene very 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 in vivo vaginal colonization in a murine model. We have renamed Sak_1753 Group B Strep vaginal adherence protein (BvaP). The findings of this study indicate that BvaP is important in GBS colonization of the vaginal tract and may be a candidate for vaccine development.