Identifying polyamine dependent mechanisms in pneumococcal pneumonia

确定肺炎球菌肺炎的多胺依赖性机制

基本信息

  • 批准号:
    8743219
  • 负责人:
  • 金额:
    $ 23.8万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
  • 资助国家:
    美国
  • 起止时间:
  • 项目状态:
    未结题

项目摘要

Serotype variability, genomic plasticity and increasing antibiotic resistance of S. pneumoniae, pose considerable challenges for designing intervention strategies for this global public health concern. There is a need for the identification as well as characterization of novel vaccine candidates for effective immunization against pneumococcus, as the available vaccines are not effective against all serotypes. Polyamines are ubiquitous small cationic molecules necessary for pneumococcal growth and virulence. Therefore, intracellular polyamine levels are tightly regulated, thus making polyamine transport mechanisms a highly attractive focus for investigation on pathogenesis and immune responses. Our preliminary results indicate that impaired polyamine transport causes attenuation of pneumonia in mouse models. However, the pathogen-host interactions responsible for this attenuation are yet to be characterized. Our central hypothesis is that attenuation in pneumococcal pneumonia by impaired pneumococcal polyamine transport is due to the reduced virulence factor gene expression and/or reduced resistance to host innate immune responses. We will test this hypothesis by conducting the following specific aims. Specific aims: 1-identify polyamine responsive pneumococcal genes and pathways by comparing gene expression of wild type and ApotABCD S. pneumoniae (a strain with genetic deletion of polyamine transport operon) in a mouse model of pneumonia ; 2-determine the host innate immune responses to polyamine deficient pneumococcus by measuring the expression of antimicrobial proteins, acute phase proteins, opsonophagocytosis by macrophages and neutrophils, and host signaling pathways and functions including Toll-like receptor signaling, using proteomics. Successful completion ofthe proposed studies will identify the pneumococcal molecular mechanisms responsive to polyamine transport as well as specific host innate immune responses. Project results will shed light on the role of polyamines in infectious diseases in general for the identification of unique intra and extracellular targets for design of novel vaccines or therapeutics in future.
肺炎链球菌的血清型变异、基因组可塑性和不断增加的抗生素耐药性,为设计针对这一全球公共卫生问题的干预策略提出了相当大的挑战。由于现有的疫苗并非对所有血清型都有效,因此有必要鉴定和鉴定用于有效免疫肺炎球菌的新型候选疫苗。多胺是

项目成果

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Bindu Nanduri其他文献

Bindu Nanduri的其他文献

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{{ truncateString('Bindu Nanduri', 18)}}的其他基金

Core B: Omics and Bioinformatics Core MSU COBRE Phase II
核心 B:组学和生物信息学核心 MSU COBRE II 期
  • 批准号:
    10261566
  • 财政年份:
    2013
  • 资助金额:
    $ 23.8万
  • 项目类别:
Core B: Omics and Bioinformatics Core MSU COBRE Phase II
核心 B:组学和生物信息学核心 MSU COBRE II 期
  • 批准号:
    10470187
  • 财政年份:
    2013
  • 资助金额:
    $ 23.8万
  • 项目类别:
Core B: Omics and Bioinformatics Core MSU COBRE Phase II
核心 B:组学和生物信息学核心 MSU COBRE II 期
  • 批准号:
    10004091
  • 财政年份:
    2013
  • 资助金额:
    $ 23.8万
  • 项目类别:
Identifying polyamine dependent mechanisms in pneumococcal pneumonia
确定肺炎球菌肺炎的多胺依赖性机制
  • 批准号:
    8896004
  • 财政年份:
  • 资助金额:
    $ 23.8万
  • 项目类别:
Identifying polyamine dependent mechanisms in pneumococcal pneumonia
确定肺炎球菌肺炎的多胺依赖性机制
  • 批准号:
    9119122
  • 财政年份:
  • 资助金额:
    $ 23.8万
  • 项目类别:
Identifying polyamine dependent mechanisms in pneumococcal pneumonia
确定肺炎球菌肺炎的多胺依赖性机制
  • 批准号:
    8465966
  • 财政年份:
  • 资助金额:
    $ 23.8万
  • 项目类别:

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  • 批准号:
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  • 财政年份:
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骨骼合成代谢过程中骨-脂肪相互作用
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