Akkermansia muciniphila Impacts Group B Streptococcus Vaginal Colonization

Abstract

Streptococcus agalactiae or Group B Streptococcus (GBS) is an opportunistic pathogen that asymptomatically colonizes the vaginal tract of up to 30% of healthy individuals. However, during pregnancy it is associated with adverse pregnancy outcomes, and GBS can be transmitted to the fetus in utero, or the newborn during vaginal birth, resulting in invasive neonatal disease. Previously we identified that Akkermansia muciniphila alters the dynamics of GBS vaginal colonization. However, the global effect of A. muciniphila in the female genital tract remains largely unknown, as it has predominantly been studied in the context of gastrointestinal health. Here we determine that A. muciniphila promotes GBS aggregation and attachment to human vaginal epithelial cells (hVECs). RNA-sequencing analysis revealed that A. muciniphila changed expression of 258 unique GBS genes during hVEC colonization, with many involved in cell wall/membrane/envelope biogenesis. We demonstrate that A. muciniphila-mediated increases in GBS aggregation and attachment to hVECs are dependent on GBS capsule and pili, respectively. Lastly, we found that A. muciniphila promoted GBS aggregation in the murine vaginal lumen and continual treatment with A. muciniphila reduced GBS vaginal persistence. Our results highlight the dynamic impact of A. muciniphila on GBS gene expression and vaginal colonization, as well as demonstrate the probiotic potential of A. muciniphila in the vaginal environment. IMPORTANCEGroup B Streptococcus (GBS) is a frequent colonizer of the vaginal tract of healthy people, however during pregnancy, maternal colonization is associated with adverse pregnancy outcomes. GBS is a leading cause of neonatal sepsis and meningitis and can be transmitted to a newborn during vaginal delivery or by ascension into the uterus during pregnancy. Influence of the vaginal microbiota on GBS pathogenesis remains greatly underappreciated. We have found that GBS is associated with the mucin-degrading intestinal commensal Akkermansia muciniphila, a newly identified colonizer of the vaginal tract. Significance of our research is in identifying the mechanistic impact of this commensal organism on GBS aggregation, cell adherence, and gene expression, as well as its therapeutic potential during GBS vaginal colonization. Unraveling relationships between GBS and the vaginal microbiota will improve maternal and fetal health and may enterprise the development of alternative methods to reduce GBS in utero complications and neonatal disease.