Development of a Probiotic Therapy for Limiting Group B Streptococcal Vaginal Carriage

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 DESCRIPTION (provided by applicant): Group B Streptococcus (GBS) remains a leading cause of invasive disease in neonates and certain adult populations including pregnant women. The development of GBS disease is initiated by the asymptomatic colonization of the female genital tract and during pregnancy can be associated with chorioamnionitis, puerperal endometritis and preterm labor. Approximately 20-30% of healthy women are colonized rectovaginally with GBS; the majority of infants born to these women will themselves become colonized with the bacterium. Newborn infection also results from ascending infection of the bacterium through the placental membranes to initiate infection in utero. In the United States national guidelines were published in 2002 that focused on a single strategy of universal screening for GBS carriage of pregnant women at 35-37 weeks of gestation plus intrapartum antibiotic prophylaxis for all women who are carriers. However, current routine screening and antibiotic prophylaxis have fallen short of complete prevention of GBS transmission and GBS remains a leading cause of neonatal infection. This proposal seeks to investigate the ability of Streptococcus salivarius, a predominant member of the native human oral microbiota, to control GBS colonization. Preliminary studies suggest that the bacteriocin producing S. salivarius probiotic strain K12 limits GBS growth in vitro and in vivo. Using our established mouse model of GBS vaginal colonization, mice will be colonized with GBS and then treated vaginally with K12 to determine the impact on GBS vaginal persistence. Different treatment and timing regimens will be compared as will the role of bacitracin production and the impact on the host immune response. These studies will provide fundamental insights into the potential of using a probiotic bacterium as a preventative therapy to control GBS vaginal colonization and thereby prevent its transmission to the neonate during pregnancy.