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

• 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
• 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

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），是一种 高达30%的健康个体的阴道和肠道微生物组。格林-巴利综合征会导致肺炎 脑膜炎和新生儿败血症，由母亲传染给孩子。此外，GBS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 中间型肠球菌和粪肠球菌采用VII型分泌系统（T7 SS） 细菌内或细菌间拮抗作用。对GBS基因组的分析显示， 推定的T7 SS基因座。这些基因簇编码T7 SS机制的核心组分， 以及推定的分泌的效应物/毒素。此应用程序的目标是定义函数 GBS T7 SS在阴道定植中的作用，并表征GBS T7 SS在细菌间定植中的作用。 对抗我们建议评估GBS T7 SS对GBS依从性的贡献， 使用体外人阴道细胞系的阴道上皮的侵袭和宿主反应 和GBS阴道定植的小鼠模型。我们亦会研究政府统计处的贡献 体外和人源化微生物群小鼠中T7 SS与其他微生物对GBS的竞争 模型我们的研究结果将大大推进对贡献的理解 GBS T7 SS的细菌间的相互作用，塑造宿主感染的结果。