Characterization of pneumococcal secretion chaperones required for virulence

毒力所需的肺炎球菌分泌伴侣的表征

基本信息

  • 批准号:
    9385522
  • 负责人:
  • 金额:
    $ 12.54万
  • 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:
    2017-07-01 至 2019-06-30
  • 项目状态:
    已结题

项目摘要

Characterization of pneumococcal secretion chaperones required for virulence Streptococcus pneumoniae is a Gram-positive pathogen that spreads through airborne droplets and colonizes the human nasopharynx where asymptomatic carriage is a prerequisite for invasive disease. S. pneumoniae is a significant health threat, globally causing more deaths than any other infectious disease. In order for S. pneumoniae to colonize and transition into an invasive infection, the bacterium relies on the elaboration of many virulence factors that are translocated across the bacterial membrane and destined for attachment to the cell wall or secretion into the host. Despite the pivotal importance of secreted proteins in bacterial pathogenesis, little is known about the mechanisms that regulate protein activity following membrane translocation in Gram-positive bacteria. Our laboratory identified the secretion chaperone PrsA2 in the Gram-positive bacterium Listeria monocytogenes (Lm) which is essential for virulence, and appears to be required for the proper folding and secretion of a number of virulence factors. My research has focused on the two prsA alleles of Lm: prsA1 and prsA2 that both have peptidyl-prolyl isomerase (PPIase) domains in addition to a foldase domain. We solved the crystal structure of Lm PrsA1 and I deciphered how structural features of PrsA1 and PrsA2 contribute to PPIase and chaperone activities in the organism. I have also determined that some PrsA activities are broadly conserved between species while others are highly specific. We recently solved the crystal structure of S. pneumoniae PrsA and I will use this structure to accomplish some of my research objectives to define the mechanisms that govern activity of secreted virulence factors in S. pneumoniae. Central to S. pneumoniae protein secretion are the surface exposed proteins: PrsA chaperone, HtrA protease/chaperone, and SlrA PPIase. I hypothesize that during host infection, S. pneumoniae PrsA, HtrA, and SlrA regulate proper folding, stabilization, and activity of secreted proteins which contribute to colonization and pathogenesis. In addition, surface exposed PrsA, HtrA and SlrA are potentially attractive drug targets because inhibition may increase antibiotic susceptibility while reducing virulence factor secretion. To implement my research objectives during the mentored K99 phase, I will work closely with my mentor Dr. Nancy Freitag who is an expert in the field of Gram-positive pathogenesis and my collaborator Dr. Don Morrison who is an expert in the field of S. pneumoniae molecular genetics and biology. By taking advantage of advances in proteomic analytical techniques, this award will enable me to establish a research program with the long-term objective of deciphering the mechanisms of virulence factor secretion and regulation in the Gram-positive pathogen S. pneumoniae which will also likely have broad relevance to other important Gram-positive pathogens.
肺炎球菌毒性所需分泌物伴侣的特征

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Laty Adriella Cahoon其他文献

Laty Adriella Cahoon的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Laty Adriella Cahoon', 18)}}的其他基金

Characterization of pneumococcal secretion chaperones required for virulence
毒力所需的肺炎球菌分泌伴侣的表征
  • 批准号:
    10078240
  • 财政年份:
    2020
  • 资助金额:
    $ 12.54万
  • 项目类别:
Characterization of pneumococcal secretion chaperones required for virulence
毒力所需的肺炎球菌分泌伴侣的表征
  • 批准号:
    10046756
  • 财政年份:
    2020
  • 资助金额:
    $ 12.54万
  • 项目类别:
Functional analyses of a Listeria secretion chaperone essential for virulence
对毒力至关重要的李斯特菌分泌伴侣的功能分析
  • 批准号:
    8831246
  • 财政年份:
    2015
  • 资助金额:
    $ 12.54万
  • 项目类别:

相似海外基金

Linkage of HIV amino acid variants to protective host alleles at CHD1L and HLA class I loci in an African population
非洲人群中 HIV 氨基酸变异与 CHD1L 和 HLA I 类基因座的保护性宿主等位基因的关联
  • 批准号:
    502556
  • 财政年份:
    2024
  • 资助金额:
    $ 12.54万
  • 项目类别:
Olfactory Epithelium Responses to Human APOE Alleles
嗅觉上皮对人类 APOE 等位基因的反应
  • 批准号:
    10659303
  • 财政年份:
    2023
  • 资助金额:
    $ 12.54万
  • 项目类别:
Deeply analyzing MHC class I-restricted peptide presentation mechanistics across alleles, pathways, and disease coupled with TCR discovery/characterization
深入分析跨等位基因、通路和疾病的 MHC I 类限制性肽呈递机制以及 TCR 发现/表征
  • 批准号:
    10674405
  • 财政年份:
    2023
  • 资助金额:
    $ 12.54万
  • 项目类别:
An off-the-shelf tumor cell vaccine with HLA-matching alleles for the personalized treatment of advanced solid tumors
具有 HLA 匹配等位基因的现成肿瘤细胞疫苗,用于晚期实体瘤的个性化治疗
  • 批准号:
    10758772
  • 财政年份:
    2023
  • 资助金额:
    $ 12.54万
  • 项目类别:
Identifying genetic variants that modify the effect size of ApoE alleles on late-onset Alzheimer's disease risk
识别改变 ApoE 等位基因对迟发性阿尔茨海默病风险影响大小的遗传变异
  • 批准号:
    10676499
  • 财政年份:
    2023
  • 资助金额:
    $ 12.54万
  • 项目类别:
New statistical approaches to mapping the functional impact of HLA alleles in multimodal complex disease datasets
绘制多模式复杂疾病数据集中 HLA 等位基因功能影响的新统计方法
  • 批准号:
    2748611
  • 财政年份:
    2022
  • 资助金额:
    $ 12.54万
  • 项目类别:
    Studentship
Genome and epigenome editing of induced pluripotent stem cells for investigating osteoarthritis risk alleles
诱导多能干细胞的基因组和表观基因组编辑用于研究骨关节炎风险等位基因
  • 批准号:
    10532032
  • 财政年份:
    2022
  • 资助金额:
    $ 12.54万
  • 项目类别:
Recessive lethal alleles linked to seed abortion and their effect on fruit development in blueberries
与种子败育相关的隐性致死等位基因及其对蓝莓果实发育的影响
  • 批准号:
    22K05630
  • 财政年份:
    2022
  • 资助金额:
    $ 12.54万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Investigating the Effect of APOE Alleles on Neuro-Immunity of Human Brain Borders in Normal Aging and Alzheimer's Disease Using Single-Cell Multi-Omics and In Vitro Organoids
使用单细胞多组学和体外类器官研究 APOE 等位基因对正常衰老和阿尔茨海默病中人脑边界神经免疫的影响
  • 批准号:
    10525070
  • 财政年份:
    2022
  • 资助金额:
    $ 12.54万
  • 项目类别:
Leveraging the Evolutionary History to Improve Identification of Trait-Associated Alleles and Risk Stratification Models in Native Hawaiians
利用进化历史来改进夏威夷原住民性状相关等位基因的识别和风险分层模型
  • 批准号:
    10689017
  • 财政年份:
    2022
  • 资助金额:
    $ 12.54万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了