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

 描述(由申请人提供)：B组链球菌(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，在怀孕期间可能与绒毛膜羊膜炎、产后子宫内膜炎和早产有关。大约20%-30%的健康妇女被GBS直肠阴道定植；这些妇女所生的大多数婴儿本身也会被细菌定植。新生儿感染也是由于细菌通过胎盘膜向上感染，从而在子宫内开始感染。在美国，2002年公布了国家准则，重点是对怀孕35-37周的孕妇进行普遍筛查的单一战略，并对所有携带GBS的妇女进行产中抗生素预防。然而，目前的常规筛查和抗生素预防措施并不能完全预防GBS的传播，GBS仍然是新生儿感染的主要原因。这项建议旨在调查唾液链球菌，一种天然人类口腔微生物区系的主要成员，控制GBS定植的能力。初步研究表明，产生细菌素的唾液链球菌益生菌K12在体外和体内都限制了GBS的生长。利用我们建立的小鼠GBS阴道定植模型，用GBS定植小鼠，然后用K12阴道给药，以确定对GBS阴道定植的影响。将比较不同的治疗和时机方案，以及杆菌肽生产的作用和对宿主免疫反应的影响。这些研究将提供对使用益生菌作为预防性治疗以控制GBS阴道定植的可能性的基本见解，从而防止其在怀孕期间传播给新生儿。

 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.