The Gonococcal Fur Regulon Link to Pathogenesis

淋球菌毛皮调节子与发病机制的联系

基本信息

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
项目类别：
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

项目摘要

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.

概括淋病奈瑟氏菌是性传播感染（STI）淋病的病因学药全世界高发病疾病，每年约有1.06亿例病例。像许多人类病原体一样有机体必须适应感染期间遇到的环境，包括低pH和氧气变化和铁水平。对淋球菌中基因表达的严格控制部分由皮草蛋白，部分介导它与特定的DNA序列结合，导致基因曲目的激活或表达。我们最近报告说，淋球菌的常规延伸至其他调节蛋白，这些蛋白共同有助于发病机理的淋球菌机制。我们还确定了毛皮的子集在天然淋球菌感染期间，受调节的基因相对于在生长期间的生长中表达体外。总体上，我们假设淋球菌的常规延伸到额外在女性生殖道中表达和调节的调节网络。提出的研究该应用程序将通过控制其他对自然感染至关重要的调节剂。我们的分析将集中于调节蛋白和SRNA 1）通过皮毛控制（直接或间接）和2）在人类自然感染期间受到调节。我们称这些“在体内表达的淋球菌调节剂”（Greiv）。提出了以下目标：目的1。定义毛皮控制的淋球菌调节蛋白和SRNA表达的曲目在女性生殖道的自然感染期间。目标2。要表征新确定的作用淋病链球菌与上皮细胞和先天免疫细胞的毛发控制的绿色相互作用。目标3。为了完全定义女性自然感染期间表达的淋球菌全球调节网络生殖器。