Function of the type 7 secretion system in Group B Streptococcus

无乳链球菌，俗称B群链球菌(GBS)，是 高达30%的健康人的阴道和肠道微生物群。GBS会导致肺炎， 从母亲传染给孩子的新生儿脑膜炎和败血症。此外，GBS还可以 在免疫功能低下的成年人和老年人中引起一系列疾病，包括尿路 感染、肺炎和脑膜炎。GBS必须与其他微生物组成员在 人类宿主的不同生态位。其他药剂、金黄色葡萄球菌、链球菌 中间菌和粪肠球菌使用VII型分泌系统(T7SS)进行 细菌内或细菌间的拮抗作用。对GBS基因组的分析揭示了 推测为T7SS基因座。这些基因簇将T7SS机制的核心组件编码为 以及推测的分泌效应物/毒素。此应用程序的目标是定义函数 GBS T7SS在阴道定植中的作用及其在细菌间的作用 对抗性。我们建议评估GBS T7SS对GBS遵守的贡献， 用体外培养的人阴道细胞系研究阴道上皮侵袭和宿主反应 GBS阴道定植的小鼠模型。我们还将研究GBS的贡献 T7SS与其他微生物在体外和人源化微生物区系小鼠中对GBS的竞争 模特们。我们的研究结果将极大地促进对这一贡献的理解 GBS T7SS的作用与细菌间的相互作用有关，从而影响宿主感染的结果。

Streptococcus agalactiae, commonly known as Group B Streptococcus (GBS), is a member of the vaginal and gut microbiome of up to 30% of healthy individuals. GBS can cause pneumonia, meningitis, and sepsis in neonates when transmitted from mother to child. In addition, GBS can cause a range of diseases in immunocompromised adults and the elderly, including urinary tract infections, pneumonia, and meningitis. GBS has to compete with other microbiome members in different niches of the human host. Other Firmicutes, Staphylococcus aureus, Streptococcus intermedius, and Enterococcus faecalis, employ the Type VII Secretion Systems (T7SS) for intrabacterial or interbacterial antagonism. Analyses of GBS genomes revealed the presence of putative T7SS loci. These gene clusters encode the core components of T7SS machinery as well as putative secreted effectors/toxins. The goals of this application are to define the function of GBS T7SS in vaginal colonization and to characterize the role of GBS T7SS in interbacterial antagonism. We propose to assess the contribution of the GBS T7SS to GBS adherence, invasion, and host responses of the vaginal epithelium using in vitro human vaginal cell lines and mouse models of GBS vaginal colonization. We will also study the contribution of the GBS T7SS to GBS competition with other microbes in vitro and in humanized microbiota mouse models. The results of our study will significantly advance the understanding of the contribution of GBS T7SS to interbacterial interactions that shape the outcome of the host infection.