Function of the type 7 secretion system in Group B Streptococcus

B 族链球菌 7 型分泌系统的功能

基本信息

批准号：
10598223
负责人：
Konstantin V Korotkov
金额：
$ 24.79万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-11-07 至 2024-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10598223
关键词：
Abscess Adherence Adult Antibiotic Prophylaxis Antibiotic Resistance Bacteria Bacterial Infections Biochemical Bioreactors Blood - brain barrier anatomy Cell Line Cells Communities Complex Core Protein Cytolysis Development Disease Ecosystem Elderly Enterococcus faecalis Epithelium Family Female Firmicutes Foundations Future Gastrointestinal tract structure Gene Cluster Genome Goals Gram-Positive Bacteria Hand Human Immune response Immunocompromised Host In Vitro Individual Infection Invaded Life Measures Mediating Meningitis Microbe Molecular Mothers Mucous Membrane Mus Newborn Infant Nutrient Organism Outcome Pathway interactions Pelvis Play Pneumonia Pregnant Women Preventive measure Process Proteins Research Design Role Route Sepsis Shapes Solid Staphylococcus aureus Streptococcal Infections Streptococcus Streptococcus Group B Streptococcus intermedius Surface System Testing Time Toxic effect Toxin Urinary tract Urinary tract infection Vagina Vertical Disease Transmission Virulence antagonist antitoxin clinically relevant cytotoxicity experimental study genetic approach genomic locus gut microbiome human microbiota in vivo member microbiome components microbiota microorganism mouse model neonatal infection neonate pathobiont pathogen prevent reproductive tract translational model transmission process uptake vaginal microbiome vaginal microbiota

项目摘要

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.

无乳链球菌，俗称 B 族链球菌 (GBS)，是以下细菌的成员：多达 30% 的健康个体的阴道和肠道微生物组。 GBS可引起肺炎，脑膜炎和新生儿败血症（母婴传播）。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，包括泌尿道疾病感染、肺炎和脑膜炎。 GBS 必须与其他微生物组成员竞争人类宿主的不同生态位。其他厚壁菌门、金黄色葡萄球菌、链球菌 intermedius 和粪肠球菌采用 VII 型分泌系统 (T7SS) 细菌内或细菌间的拮抗作用。 GBS 基因组分析揭示了推定的 T7SS 位点。这些基因簇将 T7SS 机器的核心组件编码为以及假定的分泌效应物/毒素。该应用程序的目标是定义函数 GBS T7SS 在阴道定植中的作用并表征 GBS T7SS 在细菌间的作用对抗。我们建议评估 GBS T7SS 对 GBS 遵守的贡献，使用体外人阴道细胞系对阴道上皮的侵袭和宿主反应以及 GBS 阴道定植的小鼠模型。我们还将研究 GBS 的贡献 T7SS 到 GBS 与其他微生物在体外和人源化微生物群小鼠中的竞争模型。我们的研究结果将显着促进对贡献的理解 GBS T7SS 与细菌间相互作用的关系决定了宿主感染的结果。