Role of PrrF and PrrH regulation in Pseudomonas aeruginosa pathogenesis
Role of PrrF and PrrH regulation in Pseudomonas aeruginosa pathogenesis
批准号:
9756297
负责人:
Amanda Gail Oglesby
金额:
$42.52万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-09-23 至 2021-08-31
关键词:
AcuteAntibioticsBiochemicalBiochemical GeneticsChronicClinicalCystic FibrosisDevelopmentEventGene ExpressionGene Expression RegulationGeneticGoalsHemeHomeostasisHuman bodyIn VitroIndividualInfectionIronLaboratory ResearchLifeLinkLung infectionsMalignant NeoplasmsMediatingMessenger RNAMicrobial BiofilmsMolecularMusMutateNutrientOutcomePathogenesisPathway interactionsPatientsPharmaceutical PreparationsPhenotypePhysiologyPlayProductionPropertyPseudomonas InfectionsPseudomonas aeruginosaPseudomonas aeruginosa infectionPublishingPulmonary FibrosisRNARNA analysisRegulationRegulatory PathwayResearchResistanceRoleSmall RNASourceSputumSystemTestingVeinsVirulenceVirulence FactorsWorkacute infectionantimicrobialattenuationbacterial geneticsbasebiophysical analysischronic infectioncystic fibrosis patientsexpectationin vivomutantnovelnovel therapeuticspathogenic bacteriapatient populationprogramspublic health prioritiesquorum sensingresponsetraituptake
中文摘要
项目总结
英文摘要
PROJECT SUMMARY
Pseudomonas aeruginosa is a versatile bacterial pathogen that causes life-threatening acute and chronic
infections in diverse patient populations. Complicating treatment is the ability of P. aeruginosa to resist the
majority of antimicrobial therapies. It is therefore critical to identify virulence properties that can be targeted for
the development of novel therapeutics. Several studies demonstrate the importance of iron homeostasis for P.
aeruginosa pathogenesis. Recent work from our lab shows that the P. aeruginosa prrF chromosomal locus,
which encodes the iron-responsive PrrF1 and PrrF2 small regulatory RNAs (sRNAs), is required for acute lung
infection in mice. The PrrF1 and PrrF2 sRNAs contribute to iron homeostasis by repressing the expression of
iron-utilizing pathways when this nutrient is limiting. This “iron sparing response” further impacts diverse
virulence properties, including quorum sensing and biofilm formation. The prrF locus produces a distinct sRNA
(PrrH) that is regulated by heme, an abundant source of iron in the human body, thus linking iron and heme
homeostasis pathways of P. aeruginosa. While our studies have established the broad impact of this locus on
P. aeruginosa physiology and virulence, the mechanisms by which the individual sRNAs transcribed from this
locus mediate gene expression and pathogenesis remain unknown. Based on our preliminary and published
studies, we hypothesize that the PrrF and PrrH sRNAs play critical yet distinct roles in regulating P.
aeruginosa iron homeostasis and virulence. We will test our hypothesis by 1) identifying PrrF target mRNAs
responsible for virulence attenuation of the ΔprrF1,2 mutant; 2) determining the genetic basis of heme
regulated expression via the PrrH sRNA; and 3) defining the mechanisms by which PrrF and PrrH regulate
gene expression. These studies will define the specific mechanisms by which the prrF-transcribed sRNAs
mediate iron homeostasis and virulence of P. aeruginosa.
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会议论文
UMB IMSD
-
批准号:10550221
-
项目类别:
-
资助金额:$23.75万
-
财政年份:2022
-
负责人:Amanda Gail Oglesby
-
依托单位:
UMB IMSD
-
批准号:10370923
-
项目类别:
-
资助金额:$23.32万
-
财政年份:2022
-
负责人:Amanda Gail Oglesby
-
依托单位:
Integration of heme acquisition and signaling in Gram-negative pathogens
-
批准号:10378657
-
项目类别:
-
资助金额:$47.27万
-
财政年份:2021
-
负责人:Amanda Gail Oglesby
-
依托单位:
Integration of heme acquisition and signaling in Gram-negative pathogens
-
批准号:10591561
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项目类别:
-
资助金额:$48.05万
-
财政年份:2021
-
负责人:Amanda Gail Oglesby
-
依托单位:
Integration of heme acquisition and signaling in Gram-negative pathogens
-
批准号:10756872
-
项目类别:
-
资助金额:$1.87万
-
财政年份:2021
-
负责人:Amanda Gail Oglesby
-
依托单位:
Integration of heme acquisition and signaling in Gram-negative pathogens
-
批准号:10772354
-
项目类别:
-
资助金额:$6.32万
-
财政年份:2021
-
负责人:Amanda Gail Oglesby
-
依托单位:
Mechanism of heme regulation of a P. aeruginosa non-coding RNA
-
批准号:8111461
-
项目类别:
-
资助金额:$15.91万
-
财政年份:2012
-
负责人:Amanda Gail Oglesby
-
依托单位:
Mechanism of heme regulation of a P. aeruginosa non-coding RNA
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批准号:8477120
-
项目类别:
-
资助金额:$10.5万
-
财政年份:2012
-
负责人:Amanda Gail Oglesby
-
依托单位:
海外基金