Molecular Mechanisms of anti-bacterial contact-dependent growth inhibition (CDI)
Molecular Mechanisms of anti-bacterial contact-dependent growth inhibition (CDI)
批准号:
9207766
负责人:
Christopher S. Hayes
金额:
$37.01万
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:
2016-02-01 至 2020-01-31
关键词:
AdhesionsAnti-Bacterial AgentsArchitectureBacteriaBindingBiochemicalBiochemistryC-terminalCell CommunicationCell surfaceCellsCellular StructuresChimera organismComplexCytosolDataDatabasesDevelopmentDistributed SystemsEcologyElectronsEscherichia coliEvolutionFamilyFiberFilamentGeneticGram-Negative BacteriaGrowthHumanImmunityIntegral Membrane ProteinLengthMapsMediatingMembraneMembrane ProteinsModelingMolecularMolecular GeneticsMolecular ModelsN-terminalPathway interactionsPeptide HydrolasesPositioning AttributeProtein SecretionProteinsReceptor CellResearchStructureSurfaceSurveysSynapsesSystemTestingToxinWorkalpha Toxinantimicrobialextracellularinhibitor/antagonistinsightmolecular modelingnovelnovel strategiespathogenperiplasmprotein Epublic health relevancereceptorreceptor bindingtomography
中文摘要
描述(由申请人提供):细菌已经进化出复杂的策略来相互竞争和交流。细菌间竞争的一个重要机制是由接触依赖性生长抑制(CDI)系统介导的。CDI系统存在于多种革兰氏阴性细菌中,包括许多重要的人类病原体。CDI由双伴侣分泌蛋白的CdiB/CdiA家族介导。CdiB是Omp 85外膜蛋白,其是将CdiA外蛋白输出和组装到细胞表面上所需的。CdiA与易感细菌上的受体结合,然后将其C-末端毒素结构域(CdiA-CT)递送到靶细胞中。CDI系统还编码CdiI免疫蛋白,其特异性结合CdiA-CT并中和毒素活性,从而保护CDI+细胞免受自身抑制。值得注意的是,CdiA-CT序列在细菌之间高度可变,相应的CdiI免疫蛋白也是如此。目前的分析表明,CDI系统编码至少120个不同的CDI毒素免疫家族。本申请提出了遗传、生物化学和超微结构分析的组合,以获得对CDI期间细胞-细胞相互作用和CdiA-CT毒素递送的机制见解。这项研究将大大
增加我们对细菌病原体的生态学和进化的理解,并可以为抗菌治疗提供新的方法。
英文摘要
DESCRIPTION (provided by applicant): Bacteria have evolved complex strategies to compete and communicate with one another. One important mechanism of inter-bacterial competition is mediated by contact-dependent growth inhibition (CDI) systems. CDI systems are found in a wide variety of Gram-negative bacteria, including many important human pathogens. CDI is mediated by the CdiB/CdiA family of two-partner secretion proteins. CdiB is an Omp85 outer-membrane protein that is required for the export and assembly of the CdiA exoprotein onto the cell surface. CdiA binds to receptors on susceptible bacteria and then delivers its C-terminal toxin domain (CdiA- CT) into the target cell. CDI systems also encode CdiI immunity proteins, which specifically bind to the CdiA- CT and neutralize toxin activity, thereby protecting CDI+ cells from auto-inhibition. Remarkably, CdiA-CT sequences are highly variable between bacteria, as are the corresponding CdiI immunity proteins. Current analysis indicates that CDI systems encode at least 120 distinct CDI toxin-immunity families. This application proposes a combination of genetic, biochemical and ultrastructural analyses to gain mechanistic insights into cell-cell interactions and CdiA-CT toxin delivery during CDI. This research will significantly
increase our understanding of the ecology and evolution of bacterial pathogens and could inform novel approaches to antimicrobial therapy.
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Molecular Mechanisms of anti-bacterial contact-dependent growth inhibition (CDI)
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批准号:10115747
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项目类别:
-
资助金额:$38.93万
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财政年份:2016
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负责人:Christopher S. Hayes
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依托单位:
Molecular Mechanisms of anti-bacterial contact-dependent growth inhibition (CDI)
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批准号:10360608
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项目类别:
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资助金额:$38.93万
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财政年份:2016
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负责人:Christopher S. Hayes
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依托单位:
Molecular Mechanisms of anti-bacterial contact-dependent growth inhibition (CDI)
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批准号:10588224
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项目类别:
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资助金额:$38.93万
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财政年份:2016
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负责人:Christopher S. Hayes
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依托单位:
Molecular determinants of A-site mRNA cleavage during ribosome pausing
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批准号:7924969
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项目类别:
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资助金额:$15.35万
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财政年份:2009
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负责人:Christopher S. Hayes
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依托单位:
Molecular determinants of A-site mRNA cleavage during ribosome pausing
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批准号:8500345
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项目类别:
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资助金额:$25.79万
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财政年份:2006
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负责人:Christopher S. Hayes
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依托单位:
Molecular determinants of A-site mRNA cleavage during ribosome pausing
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批准号:7643347
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项目类别:
-
资助金额:$25.25万
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财政年份:2006
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负责人:Christopher S. Hayes
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依托单位:
Molecular determinants of A-site mRNA cleavage during ribosome pausing
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批准号:7251518
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项目类别:
-
资助金额:$25.14万
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财政年份:2006
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负责人:Christopher S. Hayes
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依托单位:
Molecular determinants of A-site mRNA cleavage during ribosome pausing
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批准号:7880817
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项目类别:
-
资助金额:$24.47万
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财政年份:2006
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负责人:Christopher S. Hayes
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依托单位:
Molecular determinants of A-site mRNA cleavage during ribosome pausing
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批准号:8690897
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项目类别:
-
资助金额:$26.51万
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财政年份:2006
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负责人:Christopher S. Hayes
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依托单位:
Molecular determinants of A-site mRNA cleavage during ribosome pausing
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批准号:8324585
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项目类别:
-
资助金额:$26.92万
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财政年份:2006
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负责人:Christopher S. Hayes
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依托单位:
Molecular determinants of A-site mRNA cleavage ribosome
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批准号:7137972
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项目类别:
-
资助金额:$27.97万
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财政年份:2006
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负责人:Christopher S. Hayes
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依托单位:
Molecular determinants of A-site mRNA cleavage during ribosome pausing
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批准号:7448696
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项目类别:
-
资助金额:$25.01万
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财政年份:2006
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负责人:Christopher S. Hayes
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依托单位:
Molecular determinants of A-site mRNA cleavage during ribosome pausing
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批准号:8187755
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项目类别:
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资助金额:$27.09万
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财政年份:2006
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负责人:Christopher S. Hayes
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依托单位:
海外基金