Shigella mediated regulation of epithelial cell inflammasomes

志贺氏菌介导的上皮细胞炎症小体的调节

基本信息

  • 批准号:
    10608342
  • 负责人:
  • 金额:
    $ 76.16万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-04-14 至 2028-03-31
  • 项目状态:
    未结题

项目摘要

Shigella species are important, highly infectious pathogens of humans. In 2016, there were ~269 million cases and 212,000 deaths due to Shigella. Infection with Shigella is associated with inflammation due to the recruitment of neutrophils to the colon and massive tissue destruction. Despite this impressive host response, Shigella survive in this harsh environment, primarily by replicating within and spreading between colonic epithelial cells (ECs). Shigella survive by directly usurping and reprogramming host cell processes through the activity of ~30 type III effectors, proteins that they directly inject into the host cell cytosol via a highly conserved type III secretion system (T3SS). Our research's overall goal is to use Shigella as a model pathogen to decipher the mechanisms that enable intracellular pathogens to evade host innate immune responses and establish a replicative niche with the cytosol of intestinal ECs. We have a long-standing interest in identifying and deciphering roles for effectors in specific steps in Shigella pathogenesis. The first line of defense that Shigella and other enteric pathogens face upon trying to establish a replicative niche within the gastrointestinal tract is the induction of the death of intestinal ECs via pyroptosis. Pyroptosis is an inflammatory form of cell death that, if not inhibited, results in the rapid lysis and/or expulsion of infected ECs from the intestinal epithelium and the processing and release of pro- inflammatory cytokines. Here, we propose to investigate how Shigella type III secreted effectors cooperate to inhibit pyroptosis, thus enabling this professional intracytoplasmic pathogen to establish a replicative niche within the cytosol of intestinal epithelial cells. These studies are designed to significantly expand our understanding of how Shigella, and likely other enteric pathogens, inhibit inflammasomes. At the completion of the proposed aims, it is expected that the knowledge gained can be applied towards the development of novel host-based interventions for the prevention and treatment of enteric infections, a particularly pressing need given emerging issues with antibiotic resistance.
志贺氏菌是人类重要的高传染性病原体。2016年,约有2.69亿例

项目成果

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CAMMIE LESSER其他文献

CAMMIE LESSER的其他文献

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{{ truncateString('CAMMIE LESSER', 18)}}的其他基金

Designer EcN for treatment of solid tumors
用于治疗实体瘤的 Designer EcN
  • 批准号:
    10459848
  • 财政年份:
    2022
  • 资助金额:
    $ 76.16万
  • 项目类别:
Designer EcN for treatment of solid tumors
用于治疗实体瘤的 Designer EcN
  • 批准号:
    10565935
  • 财政年份:
    2022
  • 资助金额:
    $ 76.16万
  • 项目类别:
Designer probiotics for prevention of cholera
用于预防霍乱的设计师益生菌
  • 批准号:
    9896226
  • 财政年份:
    2020
  • 资助金额:
    $ 76.16万
  • 项目类别:
Designer probiotics for prevention of cholera
用于预防霍乱的设计师益生菌
  • 批准号:
    10092926
  • 财政年份:
    2020
  • 资助金额:
    $ 76.16万
  • 项目类别:
Dissecting the means by which type 3 substrates are defined & secreted
剖析 3 类底物的定义方式
  • 批准号:
    10328544
  • 财政年份:
    2019
  • 资助金额:
    $ 76.16万
  • 项目类别:
Dissecting the means by which type 3 substrates are defined & secreted
剖析 3 类底物的定义方式
  • 批准号:
    10274790
  • 财政年份:
    2019
  • 资助金额:
    $ 76.16万
  • 项目类别:
Dissecting the means by which type 3 substrates are defined & secreted
剖析 3 类底物的定义方式
  • 批准号:
    10411510
  • 财政年份:
    2019
  • 资助金额:
    $ 76.16万
  • 项目类别:
Dissecting the means by which type 3 substrates are defined & secreted
剖析 3 类底物的定义方式
  • 批准号:
    10553659
  • 财政年份:
    2019
  • 资助金额:
    $ 76.16万
  • 项目类别:
Dissecting the means by which type 3 substrates are defined & secreted
剖析 3 类底物的定义方式
  • 批准号:
    10589974
  • 财政年份:
    2019
  • 资助金额:
    $ 76.16万
  • 项目类别:
PIPs: a new means to identify effector-target interactions
PIP:识别效应器-目标相互作用的新方法
  • 批准号:
    8777643
  • 财政年份:
    2014
  • 资助金额:
    $ 76.16万
  • 项目类别:

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