Integration of redox-balancing mechanisms in Pseudomonas aeruginosa biofilms
铜绿假单胞菌生物膜中氧化还原平衡机制的整合
基本信息
- 批准号:9902315
- 负责人:
- 金额:$ 39.96万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-05-20 至 2023-04-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAerobicAffectAgarAirAnaerobic BacteriaAntibiotic ResistanceAntibioticsAntibodiesAntimicrobial susceptibilityBacteriaBacterial InfectionsBehaviorBindingBiochemicalBiological AssayCarbonCellsChemicalsCommunitiesComplementCrystallizationCuesDevelopmentDiseaseDrug resistanceElectronsEnergy-Generating ResourcesEnzymesEquilibriumExtracellular MatrixExtracellular StructureFluorescence MicroscopyGenerationsGeneticGoalsGrowthGuanosine MonophosphateHomeostasisHospitalsImageInfectionInvestigationIsomerismLactate DehydrogenaseLinkLiquid substanceLung infectionsMediatingMediator of activation proteinMetabolicMetabolismMicrobial BiofilmsMicroscopicMicroscopyModelingMolecularMorphogenesisMorphologyMusMycosesOxidantsOxidation-ReductionOxidesOxygenPathogenicityPathway interactionsPeriodicityPhenazinesPhysiologicalPhysiologyPredispositionProductionProteinsPseudomonas aeruginosaPyruvateRegulationResistanceResolutionRespiratory ChainRoleSignal TransductionSiteSourceStandardizationStructureSuspensionsTechniquesTestingVirulenceWorkantimicrobial drugappendagebasecell communitycystic fibrosis patientsdefined contributiondimerelectron donorfeedinggenetic approachgenetic regulatory proteinin vivoinnovationinsightmicrobial communitypathogenresponsetherapeutic target
项目摘要
Although a diverse arsenal of antimicrobial drugs has been developed, bacterial and fungal infections remain
prevalent worldwide. The formation of multicellular communities of microbes, called biofilms, is a common
feature of these diseases that contributes to their endurance. Cells in biofilms are held together by an
extracellular matrix and differ from those grown in liquid cultures with respect to their metabolism and
sensitivity to antimicrobial drugs. Our long-term goal is to define the integrated, redox-based regulatory
networks and metabolisms that support survival of bacteria in biofilms, with a focus on the pathogen
Pseudomonas aeruginosa. We hypothesize that the changing redox states of cells in developing biofilms affect
multicellular behavior, virulence, and susceptibility to antibiotics. A standardized colony biofilm morphology
assay facilitates our investigation of mechanisms that underpin biofilm-specific metabolism and feature
formation. We will use basic molecular approaches combined with newly developed and innovative techniques,
including electrochemical and microscopic analysis of biofilms at the micron scale, to address fundamental
questions regarding the use of redox-active substrates for metabolism and the global regulation of biofilm
matrix in response to redox cues: (1) How does P. aeruginosa balance its cellular redox state in the oxygen-
limited regions of biofilms? (2) How does redox control of cellular signaling determine overall community
morphology and cellular arrangement within the biofilm? (3) How does the use of pyruvate and lactate,
important energy sources and metabolic intermediates, contribute to survival in biofilms and metabolism during
host infection? As P. aeruginosa is a major cause of infections in hospitals and in patients with cystic fibrosis,
we are motivated by the potential for these mechanisms to serve as therapeutic targets.
尽管已经开发出多种抗菌药物,但细菌和真菌感染仍然存在
流行于全世界。多细胞微生物群落(称为生物膜)的形成是一种常见的现象
这些疾病的特征有助于他们的耐力。生物膜中的细胞通过
细胞外基质,在代谢和代谢方面与液体培养物中生长的不同
对抗菌药物的敏感性。我们的长期目标是定义基于氧化还原的综合监管
支持生物膜中细菌生存的网络和新陈代谢,重点是病原体
铜绿假单胞菌。我们假设正在发育的生物膜中细胞氧化还原状态的变化会影响
多细胞行为、毒力和对抗生素的敏感性。标准化菌落生物膜形态
测定有助于我们研究支持生物膜特异性代谢和特征的机制
形成。我们将使用基本的分子方法与新开发的创新技术相结合,
包括微米级生物膜的电化学和显微分析,以解决根本问题
关于使用氧化还原活性底物进行代谢和生物膜全局调节的问题
响应氧化还原线索的基质:(1)铜绿假单胞菌如何平衡其在氧中的细胞氧化还原状态
生物膜的有限区域? (2) 细胞信号传导的氧化还原控制如何决定整个群落
生物膜内的形态和细胞排列? (3) 丙酮酸和乳酸如何使用,
重要的能量来源和代谢中间体,有助于生物膜的存活和代谢过程
宿主感染?由于铜绿假单胞菌是医院和囊性纤维化患者感染的主要原因,
这些机制作为治疗靶点的潜力激励着我们。
项目成果
期刊论文数量(0)
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Lars Dietrich其他文献
Lars Dietrich的其他文献
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{{ truncateString('Lars Dietrich', 18)}}的其他基金
Integration of redox-balancing mechanisms in Pseudomonas aeruginosa biofilms
铜绿假单胞菌生物膜中氧化还原平衡机制的整合
- 批准号:
8577604 - 财政年份:2013
- 资助金额:
$ 39.96万 - 项目类别:
Integration of redox-balancing mechanisms in Pseudomonas aeruginosa biofilms
铜绿假单胞菌生物膜中氧化还原平衡机制的整合
- 批准号:
9916038 - 财政年份:2013
- 资助金额:
$ 39.96万 - 项目类别:
Integration of redox-balancing mechanisms in Pseudomonas aeruginosa biofilms
铜绿假单胞菌生物膜中氧化还原平衡机制的整合
- 批准号:
8975486 - 财政年份:2013
- 资助金额:
$ 39.96万 - 项目类别:
Integration of redox-balancing mechanisms in Pseudomonas aeruginosa biofilms
铜绿假单胞菌生物膜中氧化还原平衡机制的整合
- 批准号:
10391571 - 财政年份:2013
- 资助金额:
$ 39.96万 - 项目类别:
Integration of redox-balancing mechanisms in Pseudomonas aeruginosa biofilms
铜绿假单胞菌生物膜中氧化还原平衡机制的整合
- 批准号:
9038966 - 财政年份:2013
- 资助金额:
$ 39.96万 - 项目类别:
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