The BspC surface adhesin and gastrointestinal fungal colonization enhance group B streptococcal neonatal infection

ABSTRACT Group B Streptococcus (GBS) colonizes the gastrointestinal (GI) and female reproductive tracts of up to 30% of healthy adults, but during pregnancy can be transmitted to the newborn, causing neonatal sepsis, pneumonia, and meningitis. Neonatal GI colonization is an important precursor to invasive disease, yet the mechanisms governing GBS intestinal persistence and dissemination are still being elucidated. Given the predominance of hypervirulent sequence type 17 (ST-17) strains in neonatal invasive disease, we hypothesized that the ST-17-associated surface adhesin BspC contributes to gastrointestinal colonization and infection. Using a neonatal mouse model, we found that pups infected with wild-type GBS exhibited increased mortality and significantly higher bacterial burdens in the intestine, blood, spleen, and brain compared with pups infected with a Δ bspC mutant. We also observed that BspC promoted adherence to a 2D organoid model of the human infant colon and Caco-2 intestinal epithelial cells through its variable domain. Building on previous findings that Candida albicans interacts with BspC, we found that C. albicans enhanced GBS intestinal epithelial adherence in a BspC-dependent manner, and coinfection increased intestinal GBS burden and brain dissemination in neonatal mice. Finally, analysis of published human neonatal fecal microbiome data sets revealed higher GBS abundance in infants colonized with C. albicans or other Candida species. Together, these findings identify BspC as a key mediator of GBS intestinal colonization and invasive disease and suggest that fungal colonization of the neonatal GI promotes GBS pathogenesis. IMPORTANCE Group B Streptococcus (GBS) is a leading cause of neonatal infection, which can result in fatality or long-term neurological morbidity in survivors. Intestinal colonization is an important precursor to invasive disease, yet the factors that promote GBS persistence in the neonatal gastrointestinal tract remain incompletely understood. Here, we identify the GBS surface adhesin BspC as a mediator of intestinal epithelial adherence, gastrointestinal colonization, and systemic dissemination. We further demonstrate that the common fungal pathobiont Candida albicans enhances GBS intestinal adherence and infection. Consistent with our experimental findings, analysis of human infant microbiome data sets revealed greater GBS abundance in infants colonized with Candida species. These findings identify BspC as a key mediator of this process and suggest that fungal colonization can enhance GBS disease.