Group B streptococcal (GBS) infections are a leading cause of neonatal morbidity and mortality worldwide: a recent metanalysis reveals that the annual global GBS burden contributes up to 3.5 million preterm births, 320,000 cases of neonatal infection, and 50,000 stillbirths. Third trimester rectovaginal colonization is the primary risk factor for developing invasive GBS infection, however, our understanding of host factors for that modulate colonization during pregnancy is limited. In this dissertation, I developed a novel mouse model to characterize vaginal GBS colonization dynamics in pregnancy and use it to identify host factors unique to pregnancy that regulate vaginal GBS colonization. Chapter 2 discusses a mouse model of GBS vaginal colonization in pregnancy, where nonpregnant females maintain persistent vaginal GBS carriage. However, persistently colonized females clear GBS from the vaginal tract soon after mating. Chapter 3 seeks to identify factors in early pregnancy that restrict GBS colonization and persistence. We hypothesized that exposure to seminal fluid components and increases in ovarian hormones contribute to GBS clearance. Removal of seminal vesicle fluid from male ejaculate led partially restored GBS carriage post-copulation, suggesting that seminal fluid components contribute to GBS clearance in pregnancy. Further, exogenous progesterone treatment led to substantial GBS clearance from the vaginal tract and this correlated with neutrophil influx, suggesting that progesterone is a key driver of GBS clearance in early pregnancy which may be driven by increases in vaginal neutrophils. The findings discussed in this dissertation reveal prospective novel risk factors and therapeutic interventions to treat GBS disease.
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