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:
  • 金额:
    $ 50.43万
  • 依托单位:
  • 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

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.
摘要 淋球菌是性传播感染(STI)淋病的病原体, 全世界的高发病率疾病,每年约有1.06亿例。就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 和铁的水平。淋球菌基因表达的严格控制部分是由毛皮蛋白介导的, 它与特定的DNA序列结合,导致一系列基因的激活或抑制。 我们最近报道了淋球菌毛皮调节子延伸到额外的调节蛋白,这是 共同作用于淋球菌的致病机制。我们还建立了毛发的子集 受调控的基因在女性自然淋球菌感染期间的表达相对于在 体外培养。 综合我们的结果,我们假设淋球菌毛皮调节基因延伸到另一个 在女性生殖道中表达和调节的调节网络。建议进行的研究 此应用程序将定义如何通过控制其他 对自然感染至关重要的监管机构。我们的分析将集中在调节蛋白和sRNA上。 它们是1)通过毛皮(直接或间接)控制的,2)在人类自然感染期间受到调节的。 我们称之为“体内表达的淋球菌调节因子”(GREIV)。建议的目标如下: 目的1.确定毛发控制的淋球菌调节蛋白和sRNA的表达谱 在女性生殖道自然感染期间。目标2.描述新确定的角色 淋病奈瑟菌皮毛控制的GREIV与上皮细胞和天然免疫细胞的相互作用。目标3. 充分确定淋球菌在女性自然感染期间表达的全球调控网络 生殖器。

项目成果

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Caroline A Genco其他文献

Caroline A Genco的其他文献

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{{ truncateString('Caroline A Genco', 18)}}的其他基金

Porphyromonas gingivalis and Pancreatic Carcinogenesis in Mouse Models
小鼠模型中牙龈卟啉单胞菌与胰腺癌发生
  • 批准号:
    9519194
  • 财政年份:
    2018
  • 资助金额:
    $ 50.43万
  • 项目类别:
Microbial Disruption of Dendritic Cell Maturation and Function
树突状细胞成熟和功能的微生物破坏
  • 批准号:
    10237941
  • 财政年份:
    2018
  • 资助金额:
    $ 50.43万
  • 项目类别:
Microbial Disruption of Dendritic Cell Maturation and Function
树突状细胞成熟和功能的微生物破坏
  • 批准号:
    10468732
  • 财政年份:
    2018
  • 资助金额:
    $ 50.43万
  • 项目类别:
Microbial Disruption of Dendritic Cell Maturation and Function
树突状细胞成熟和功能的微生物破坏
  • 批准号:
    9790936
  • 财政年份:
    2018
  • 资助金额:
    $ 50.43万
  • 项目类别:
Global Transcriptome Analysis of Mucosal Gonoccal Infection
粘膜淋菌感染的全局转录组分析
  • 批准号:
    9333190
  • 财政年份:
    2016
  • 资助金额:
    $ 50.43万
  • 项目类别:
TLR4 evasion, bacterial persistence and chronic inflammation
TLR4 逃避、细菌持续存在和慢性炎症
  • 批准号:
    8926492
  • 财政年份:
    2014
  • 资助金额:
    $ 50.43万
  • 项目类别:
TLR4 evasion, bacterial persistence and chronic inflammation
TLR4 逃避、细菌持续存在和慢性炎症
  • 批准号:
    9117800
  • 财政年份:
    2014
  • 资助金额:
    $ 50.43万
  • 项目类别:
Global transcriptome analysis of mucosal gonococcal infection
粘膜淋球菌感染的全局转录组分析
  • 批准号:
    9101453
  • 财政年份:
    2014
  • 资助金额:
    $ 50.43万
  • 项目类别:
Global transcriptome analysis of mucosal gonococcal infection
粘膜淋球菌感染的全局转录组分析
  • 批准号:
    8889364
  • 财政年份:
    2014
  • 资助金额:
    $ 50.43万
  • 项目类别:
P. gingivalis Mediated Evasion Strategies
牙龈卟啉单胞菌介导的逃避策略
  • 批准号:
    8532592
  • 财政年份:
    2013
  • 资助金额:
    $ 50.43万
  • 项目类别:

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