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

 描述（由申请方提供）：B族链球菌（GBS）仍然是新生儿和某些成人人群（包括孕妇）侵袭性疾病的主要原因。GBS疾病的发展是由女性生殖道的无症状定植开始的，并且在妊娠期间可能与绒毛膜炎、产褥期子宫内膜炎和早产有关。大约20-30%的健康女性的直肠阴道定植有GBS;这些女性所生的大多数婴儿本身也会被细菌定植。新生儿感染也是由细菌通过胎盘膜上行感染引起的，从而在子宫内引发感染。在美国，2002年公布了国家指南，其重点是在妊娠35-37周时对孕妇进行GBS携带的普遍筛查以及对所有携带者的妇女进行产时抗生素预防的单一策略。然而，目前的常规筛查和抗生素预防未能完全预防GBS传播，GBS仍然是新生儿感染的主要原因。该提案旨在研究唾液链球菌（Streptococcus salivarius）（天然人类口腔微生物群的主要成员）控制GBS定殖的能力。初步研究表明，产细菌素的S。唾液益生菌菌株K12在体外和体内限制GBS生长。使用我们建立的GBS阴道定殖的小鼠模型，将用GBS定殖小鼠，然后用K12阴道处理以确定对GBS阴道持久性的影响。将比较不同的治疗和时机方案，以及杆菌肽产生的作用和对宿主免疫应答的影响。这些研究将为使用益生菌作为预防性治疗以控制GBS阴道定植并从而防止其在妊娠期间传播给新生儿的潜力提供基本见解。

 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.