Identity, function and control of Francisella effectors encoded outside its pathogenicity island
弗朗西斯菌致病岛外编码的效应子的身份、功能和控制
基本信息
- 批准号:10668260
- 负责人:
- 金额:$ 79.56万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-07-01 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AerosolsAggressive courseAnimalsBacteriaBiochemicalBioinformaticsBiologyCell membraneCellsClassificationDataDiseaseDistalDistantDoseElementsEnzymesFamilyFrancisellaFrancisella tularensisGene ExpressionGenesGeneticGenetic ScreeningGenomeGram-Negative BacteriaGrowthHomologous GeneHumanInfectionLegionellaLife StyleLinkLocationManuscriptsMediatingModelingMolecularMutagenesisNamesOrganismPIK3CG genePaperPathogenesisPathogenicityPathogenicity IslandPathway interactionsPhosphatidylinositolsPhosphotransferasesPlayProtein SecretionProteinsPublishingRegulationReportingResearchResearch PersonnelRickettsiaRoleRouteSystemTestingTularemiaVariantVesicleVibrioVirulenceVirulence FactorsVirulentWorkexperimental studyfitnessfunctional plasticityguided inquiryhuman pathogenin vivoinsightmemberpathogenpathogenic bacteriaphosphatidylinositol 3-phosphatepromoterprotein functionresponsescreeningtrafficking
项目摘要
Summary
The Francisella constitute a genus of Gram-negative bacteria that occupy intracellular niches within a wide
range of metazoan hosts. This group includes Francisella tularensis subsp. tularensis, a highly virulent human
pathogen that has been classified as a Tier 1 select agent due to its low infectious dose, aerosol route of
inoculation, and aggressive course of infection. Several studies have suggested that the key virulence factor of
these bacteria is the Francisella pathogenicity island (FPI), which encodes a variant of the bacterial type VI
secretion system (T6SS). However, the FPI is conserved among Francisella spp with diverse host ranges and
variable capacity to cause disease. In preliminary data accompanying this proposal, we demonstrate that
genes encoding substrate effector proteins of the FPI T6SS can be found at distal locations in the genome. We
further find that although these effectors are variably present in Francisella spp, they play important, direct
roles in promoting the virulence strategies of the bacteria that harbor them. These findings lead us to
hypothesize that the FPI-encoded T6SS serves as a versatile platform for the delivery of diverse effector
molecules encoded elsewhere within the genome. In our first aim we will define the molecular mechanism by
which one T6SS effector of F. tularensis, OpiA, facilitates intracellular replication. Importantly, the mode of
action of an FPI effector protein has not been identified to date. We show herein that OpiA is the founding
member of a family of bacterial phosphatidylinositol kinases with representatives in diverse pathogens
including Vibrio, Legionella, and Rickettsia spp. These data and additional preliminary findings suggest that
OpiA acts by manipulating host cell membrane trafficking. In our second aim, we seek to identify the proteins
required for targeting effectors to the T6SS in Francisella, as well as to define the mechanism by which the
secretory apparatus and its substrates are coordinately regulated. Finally, in the third aim we propose to
identify additional substrates of FPI-encoded T6SSs belonging to multiple F. tularensis subspecies and to
characterize their contribution to the pathogenesis of F. tularensis subsp. tularensis. Collectively, the proposed
research will provide insight into the virulence mechanisms of an important group of human and animal
pathogens.
总结
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)
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SIMON L DOVE其他文献
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{{ truncateString('SIMON L DOVE', 18)}}的其他基金
Identification of RNA-binding proteins in Pseudomonas aeruginosa
铜绿假单胞菌中 RNA 结合蛋白的鉴定
- 批准号:
10428914 - 财政年份:2022
- 资助金额:
$ 79.56万 - 项目类别:
Identification of RNA-binding proteins in Pseudomonas aeruginosa
铜绿假单胞菌中 RNA 结合蛋白的鉴定
- 批准号:
10613590 - 财政年份:2022
- 资助金额:
$ 79.56万 - 项目类别:
Identity, function and control of Francisella effectors encoded outside its pathogenicity island
弗朗西斯菌致病岛外编码的效应子的身份、功能和控制
- 批准号:
10187513 - 财政年份:2019
- 资助金额:
$ 79.56万 - 项目类别:
Identity, function and control of Francisella effectors encoded outside its pathogenicity island
弗朗西斯菌致病岛外编码的效应子的身份、功能和控制
- 批准号:
9796805 - 财政年份:2019
- 资助金额:
$ 79.56万 - 项目类别:
Global post-transcriptional regulators in P. aeruginosa
铜绿假单胞菌的全局转录后调节因子
- 批准号:
10524023 - 财政年份:2019
- 资助金额:
$ 79.56万 - 项目类别:
Global post-transcriptional regulators in P. aeruginosa
铜绿假单胞菌的全局转录后调节因子
- 批准号:
9895974 - 财政年份:2019
- 资助金额:
$ 79.56万 - 项目类别:
A signaling pathway governing growth and antibiotic sensitivity in Pseudomonas aeruginosa
控制铜绿假单胞菌生长和抗生素敏感性的信号通路
- 批准号:
9807023 - 财政年份:2019
- 资助金额:
$ 79.56万 - 项目类别:
Global post-transcriptional regulators in P. aeruginosa
铜绿假单胞菌的全局转录后调节因子
- 批准号:
10064125 - 财政年份:2019
- 资助金额:
$ 79.56万 - 项目类别:
Global post-transcriptional regulators in P. aeruginosa
铜绿假单胞菌的全局转录后调节因子
- 批准号:
10307628 - 财政年份:2019
- 资助金额:
$ 79.56万 - 项目类别:
Identity, function and control of Francisella effectors encoded outside its pathogenicity island
弗朗西斯菌致病岛外编码的效应子的身份、功能和控制
- 批准号:
10415911 - 财政年份:2019
- 资助金额:
$ 79.56万 - 项目类别:














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