P. aeruginosa type III secreted effectors in corneal disease

角膜疾病中铜绿假单胞菌 III 型分泌效应子

基本信息

  • 批准号:
    8404007
  • 负责人:
  • 金额:
    $ 37.29万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-01-01 至 2014-12-31
  • 项目状态:
    已结题

项目摘要

P. aeruginosa infections are a common cause of corneal disease associated with extended-wear contact lens use here in the US. One of the primary virulence factors P. aeruginosa uses to promote disease is its type III secretion system, a molecular syringe that allows the bacterium to directly inject effector proteins into targeted host cells. The role of type III secretion in corneal disease has not been studied extensively, but initial reports suggest that corneal disease depends on the complement of effectors being expressed by the infecting bacteria. "Cytotoxic" strains expressing the potent phospholipase ExoU rely extensively on type III secretion to promote disease, whereas ExoS-producing "invasive" strains, appear to not rely on type III secretion in order to elicit corneal disease. We have revisited the role of type III secretion in the pathogenesis of corneal disease elicited by ExoS+ "invasive" isolates of P. aeruginosa. Our preliminary data demonstrates that corneal disease relies critically on type III secretion and on the two effectors ExoS and ExoT, in particular. In addition, we provide evidence that the primary role of type III secretion in corneal disease is to stave off killing by infiltrating neutrophils. Accordingly, the focus of this proposal is to determine the role of the individual enzymatic activities of ExoS and ExoT in preventing clearance by neutrophils in vivo. We will correlate these findings with experiments aimed at examining the role of ExoS and ExoT in preventing phagocytic killing by isolated primary neutrophils. We will also examine the difference in pathogenesis between ExoU-expressing "cytotoxic" and ExoS- expressing "invasive" strains of P. aeruginosa in order to determine if any differences can be directly linked to the activities of these two effectors. Understanding the role of effector proteins in corneal disease is an important step towards formulating new strategies for preventing and treating P. aeruginosa infections of the eye.
铜绿假单胞菌感染是与长时间佩戴相关的角膜疾病的常见原因

项目成果

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Arne Rietsch其他文献

Arne Rietsch的其他文献

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{{ truncateString('Arne Rietsch', 18)}}的其他基金

Host cell factors controlling type III secretion effector translocation
控制III型分泌效应器易位的宿主细胞因子
  • 批准号:
    10416972
  • 财政年份:
    2022
  • 资助金额:
    $ 37.29万
  • 项目类别:
Host cell factors controlling type III secretion effector translocation
控制III型分泌效应器易位的宿主细胞因子
  • 批准号:
    10586145
  • 财政年份:
    2022
  • 资助金额:
    $ 37.29万
  • 项目类别:
Development of recombinase-based tools to study established infections
开发基于重组酶的工具来研究已确定的感染
  • 批准号:
    10201472
  • 财政年份:
    2020
  • 资助金额:
    $ 37.29万
  • 项目类别:
Development of recombinase-based tools to study established infections
开发基于重组酶的工具来研究已确定的感染
  • 批准号:
    10040615
  • 财政年份:
    2020
  • 资助金额:
    $ 37.29万
  • 项目类别:
Type III Secretion Translocon Structure and Function
III型分泌易位子的结构和功能
  • 批准号:
    8701601
  • 财政年份:
    2014
  • 资助金额:
    $ 37.29万
  • 项目类别:
P. aeruginosa type III secreted effectors in corneal disease
角膜疾病中铜绿假单胞菌 III 型分泌效应子
  • 批准号:
    8962457
  • 财政年份:
    2012
  • 资助金额:
    $ 37.29万
  • 项目类别:
P. aeruginosa type III secreted effectors in corneal disease
角膜疾病中铜绿假单胞菌 III 型分泌效应子
  • 批准号:
    8217524
  • 财政年份:
    2012
  • 资助金额:
    $ 37.29万
  • 项目类别:
P. aeruginosa type III secreted effectors in corneal disease
角膜疾病中铜绿假单胞菌 III 型分泌效应子
  • 批准号:
    8597435
  • 财政年份:
    2012
  • 资助金额:
    $ 37.29万
  • 项目类别:
P. aeruginosa type III secreted effectors in corneal disease
角膜疾病中铜绿假单胞菌 III 型分泌效应子
  • 批准号:
    9115162
  • 财政年份:
    2012
  • 资助金额:
    $ 37.29万
  • 项目类别:

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