Identification of natural products targeting new pathways in bacteria
鉴定针对细菌新途径的天然产物
基本信息
- 批准号:9052699
- 负责人:
- 金额:$ 69.92万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-05-12 至 2019-04-30
- 项目状态:已结题
- 来源:
- 关键词:AffectAnti-Bacterial AgentsAntibiotic TherapyAntibioticsBacteriaBasic ScienceCellsCollectionDataData SetDrug TargetingDrug resistanceEscherichia coliFluorescence MicroscopyFutureGenesGoalsGram-Negative BacteriaGram-Positive BacteriaHealthHourIndividualLeadMeasuresMulti-Drug ResistanceNatural ProductsOrganismPathway interactionsPeptide HydrolasesPharmaceutical PreparationsProteinsResearchResistanceTechnologyToxic effectWitbasecellular targetingcombatgenome-wideimprovedinsightinterestkillingsnew therapeutic targetnovelnovel strategiespathogenprotein profilingsafety testing
项目摘要
DESCRIPTION (provided by applicant): We developed a new approach to facilitate identification of natural products with antibacterial activities that rapidly discriminates between
different mechanisms of action (MOA). This approach, bacterial cytological profiling (BCP), uses quantitative fluorescence microscopy to measure the effects of antibiotic treatment on individual cells. Antibiotics that target different cellular pathways and different steps within a pathway generate unique cytological profiles, allowing identification of the likely MOA of new compounds within a few hours. We have now developed a complimentary approach that will allow us to identify molecules that inhibit proteins that are not currently targeted by antibacterial drugs. Ths approach, which we call rapid inhibition profiling (R.I.P.), entails the rapid, inducible depletionof a target protein, followed by cytological profiling. Our preliminary data demonstrate that depletion of a drug target by R.I.P. produces cytological effects identical to those produced by the corresponding drug. Furthermore, depletion of essential proteins that are not targeted by current antibacterial drugs produces novel cytological profiles that can be subsequently used to identify molecules that inhibit these new targets. We here propose to more fully develop the R.I.P. technology by employing it on a genome wide basis in E. coli and B. subtilis. This will create a comprehensive reference set of profiles associated with the inhibition of essential cellular pathways that are not the targets of current antibacterial drugs. The genome-wide R.I.P. analysis will also provide insight into the function of conserved genes and our preliminary data suggests that it will provide insight into proteins that coordinate two or more biosynthetic pathways, providing interesting starting points for future basic research. We will then use this more complete reference data set with BCP to screen a unique and diverse collection of natural product extracts to identify those that inhibit these new drug targets and kill multidrug resistant
bacteria. Together with our collaborators at Fundaci¿n Medina, we will then purify and characterize our highest priority lead molecules (those that kill multidrug resistant bacteria) wit a goal of advancing them into toxicity trials.
描述(由申请人提供):我们开发了一种新方法来促进鉴定具有抗菌活性的天然产物,该方法可以快速区分天然产物
不同的作用机制(MOA),这种方法,细菌细胞学分析(BCP),使用定量荧光显微镜来测量抗生素治疗对单个细胞的影响,针对不同的细胞途径和途径中的不同步骤产生独特的细胞学特征,允许在几个小时内鉴定出新化合物的可能的 MOA,我们现在开发了一种补充方法,该方法将使我们能够鉴定出抑制目前抗菌药物未靶向的蛋白质的分子,我们将其称为快速抑制。我们的初步数据表明,R.I.P. 消除药物靶点产生的细胞学效应与相应药物产生的效应相同。当前抗菌药物未靶向的蛋白质会产生新的细胞学特征,随后可用于识别抑制这些新靶点的分子。 R.I.P. 技术在大肠杆菌和枯草芽孢杆菌的基因组范围内使用,这将创建与抑制当前抗菌药物分析目标的基本细胞途径相关的综合参考集。提供对保守基因功能的深入了解,我们的初步数据表明,它将提供对协调两个或多个生物合成途径的蛋白质的深入了解,为我们随后将使用的未来基础研究提供有趣的起点。这个更完整的参考数据集与 BCP 一起筛选独特且多样化的天然产物提取物,以确定那些能够抑制这些新药物靶标并杀死多重耐药性的天然产物提取物
与我们在 Fundaci 的合作者一起。在麦地那,我们将纯化和表征我们最优先的先导分子(那些杀死多重耐药细菌的分子),目标是将它们推进毒性试验。
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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JOSEPH A POGLIANO其他文献
JOSEPH A POGLIANO的其他文献
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{{ truncateString('JOSEPH A POGLIANO', 18)}}的其他基金
Molecular and cellular biology of the phage nucleus and spindle
噬菌体核和纺锤体的分子和细胞生物学
- 批准号:
10521684 - 财政年份:2018
- 资助金额:
$ 69.92万 - 项目类别:
Molecular and cellular biology of the phage nucleus and spindle
噬菌体核和纺锤体的分子和细胞生物学
- 批准号:
10217195 - 财政年份:2018
- 资助金额:
$ 69.92万 - 项目类别:
Molecular and cellular biology of the phage nucleus and spindle
噬菌体核和纺锤体的分子和细胞生物学
- 批准号:
10710178 - 财政年份:2018
- 资助金额:
$ 69.92万 - 项目类别:
Identification of natural products targeting new pathways in bacteria
鉴定针对细菌新途径的天然产物
- 批准号:
8767927 - 财政年份:2014
- 资助金额:
$ 69.92万 - 项目类别:
Identification of natural products targeting new pathways in bacteria
鉴定针对细菌新途径的天然产物
- 批准号:
8848033 - 财政年份:2014
- 资助金额:
$ 69.92万 - 项目类别:
DNA segregation during Bacillus growth and development
芽孢杆菌生长和发育过程中的 DNA 分离
- 批准号:
7477658 - 财政年份:2006
- 资助金额:
$ 69.92万 - 项目类别:
DNA segregation during Bacillus growth and development
芽孢杆菌生长和发育过程中的 DNA 分离
- 批准号:
7492397 - 财政年份:2006
- 资助金额:
$ 69.92万 - 项目类别:
DNA segregation during Bacillus growth and development
芽孢杆菌生长和发育过程中的 DNA 分离
- 批准号:
7147786 - 财政年份:2006
- 资助金额:
$ 69.92万 - 项目类别:
DNA segregation during Bacillus growth and development
芽孢杆菌生长和发育过程中的 DNA 分离
- 批准号:
8310033 - 财政年份:2006
- 资助金额:
$ 69.92万 - 项目类别:
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