The Gonococcal Fur Regulon Link to Pathogenesis

淋球菌毛皮调节子与发病机制的联系

• 批准号: 9751634
• 负责人: Caroline A Genco
• 金额: $ 50.43万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-18 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9751634
• 关键词: Algorithms; Antibiotic Resistance; Antibiotics; Binding; Bioinformatics; Cells; China; Clinical; Complement; DNA; DNA Binding; DNA Sequence; DNA-Binding Proteins; Data Set; Disease; Ectopic Pregnancy; Environment; Epithelial Cells; Escherichia coli; Etiology; Exposure to; Family; Female; Future; Gene Expression; Gene Expression Profile; Genes; Genital system; Gonorrhea; Growth; Homologous Gene; Human; Immune; In Vitro; Individual; Infection; Infertility; Invaded; Iron; Irrigation; Lead; Link; Maps; Mediating; Morbidity - disease rate; Mucous Membrane; Mutation; Nature; Neisseria gonorrhoeae; Operator Regions; Organism; Outcome Study; Oxygen; Pathogenesis; Patients; Pelvic Inflammatory Disease; Phase; Physiological; Promoter Regions; Proteins; Regulation; Regulon; Reporting; Repression; Resistance; Role; Sexually Transmitted Agents; Sexually Transmitted Diseases; Small RNA; Specimen; Techniques; Variant; Woman; antimicrobial; base; cervicovaginal; cohort; design; dimer; experimental study; genetic regulatory protein; genital infection; global health; human pathogen; in vivo; mutant; neutrophil; novel; promoter; protein complex; reproductive tract; resistant strain; transcription factor; transcriptome; transcriptome sequencing; uptake

Summary Neisseria gonorrhoeae is the etiological agent of the sexually transmitted infection (STI) gonorrhea, a high morbidity disease worldwide with ~ 106 million cases annually. Like many human pathogens this organism must adapt to environments encountered during infection, including low pH and varying oxygen and iron levels. Tight control of gene expression in the gonococcus is mediated in part by the Fur protein, which binds to specific DNA sequences leading to either activation or repression of a repertoire of genes. We recently reported that the gonococcal Fur regulon extends to additional regulatory proteins, which together contribute to gonococcal mechanisms of pathogenesis. We also established that subsets of Fur regulated genes are expressed during natural gonococcal infection in women relative to during growth in vitro. Based collectively on our results we hypothesize that the gonococcal Fur regulon extends to additional regulatory networks that are expressed and regulated in the female genital tract. The studies proposed in this application will define how Fur-mediated regulation is extended through control of additional regulators that are crucial to natural infection. Our analysis will focus on regulatory proteins and sRNAs that are 1) Controlled via Fur (directly or indirectly) and 2) Regulated during natural infection in humans. We term these “gonococcal regulators expressed in vivo” (GREIV). The following Aims are proposed: Aim 1. To define the repertoire of Fur-controlled gonococcal regulatory proteins and sRNAs expressed during natural infection of the female genital tract. Aim 2. To characterize the role of newly identified Fur-controlled GREIV in N. gonorrhoeae interactions with epithelial cells and innate immune cells. Aim 3. To fully define gonococcal global regulatory networks expressed during natural infection of the female genital.

概括 淋病奈瑟菌是性传播感染 (STI) 淋病的病原体， 全世界发病率很高，每年约有 1.06 亿例病例。像许多人类病原体一样 生物体必须适应感染期间遇到的环境，包括低 pH 值和变化的氧气 和铁含量。淋球菌基因表达的严格控制部分是由 Fur 蛋白介导的， 它与特定的 DNA 序列结合，导致一系列基因的激活或抑制。 我们最近报道淋球菌毛皮调节子延伸到其他调节蛋白， 共同促进淋球菌的发病机制。我们还确定了 Fur 的子集 相对于生长期间，女性自然淋球菌感染期间受调节的基因表达 体外。 综合我们的结果，我们假设淋球菌毛皮调节子扩展到其他 在女性生殖道中表达和调节的调节网络。中提出的研究 该应用程序将定义如何通过控制额外的毛皮介导的调节来扩展 对自然感染至关重要的调节因子。我们的分析将重点关注调节蛋白和 sRNA 1) 通过毛皮（直接或间接）控制，2) 在人类自然感染过程中受到调节。 我们将这些称为“体内表达的淋球菌调节因子”(GREIV)。建议实现以下目标： 目标 1. 确定 Fur 控制的淋球菌调节蛋白和表达的 sRNA 的所有组成部分 在女性生殖道自然感染期间。目标 2. 描述新确定的角色的特征 淋病奈瑟菌与上皮细胞和先天免疫细胞相互作用中毛皮控制的 GREIV。目标3。 全面定义女性自然感染期间表达的淋球菌全球调控网络 生殖器。