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.

链球菌agalactiae，通常称为B组链球菌（GBS），是 高达30％的健康个体的阴道和肠道微生物组。 GB会引起肺炎， 脑膜炎和新生儿败血症从母亲传播到孩子。此外，GB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。 GB必须与其他微生物组成员竞争 人类寄主的不同壁ni。其他公司，金黄色葡萄球菌，链球菌 Intermedius和肠球菌粪便使用VII型分泌系统（T7SS） 细菌或细菌间拮抗作用。 GBS基因组的分析揭示了存在 推定的T7SS基因座。这些基因簇对T7SS机械的核心组件编码为 以及推定的分泌效应子/毒素。此应用程序的目标是定义功能 GBS T7S在阴道定植中的作用，并表征GBS T7S在细菌间的作用 对抗。我们建议评估GBS T7S对GBS依从性的贡献， 使用体外人类阴道细胞线的侵袭和阴道上皮的宿主反应 和GBS阴道定植的小鼠模型。我们还将研究GBS的贡献 在体外与其他微生物与其他微生物竞争的T7S和人源化的微生物群中 型号。我们研究的结果将大大提高对贡献的理解 GBS T7S与塑造宿主感染结果的细菌间相互作用。