Bacterial Response to Singlet Oxygen
细菌对单线态氧的反应
基本信息
- 批准号:7664969
- 负责人:
- 金额:$ 26.54万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-08-01 至 2012-07-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAlgaeAlphaproteobacteriaAmino AcidsAnimalsBacteriaBindingBinding ProteinsBioenergeticsBiological ProcessCell RespirationCellsChemicalsComplexDNA-Directed RNA PolymeraseDissociationElectron TransportElectronsEnergy TransferEukaryotic CellFamilyGene ExpressionGene TargetingGoalsHomologous GeneHumanHydrogen PeroxideHydroxyl RadicalLaboratoriesLeadLifeMembraneMicrobeMicrobial Genome SequencingModificationMolecularMutationN-terminalNatureOrganismOxidantsOxygenPathway interactionsPhotochemotherapyPhotosynthesisPlanetsPlantsProtein BindingProteinsProteobacteriaReactionReactive Oxygen SpeciesResearchRhodobacter sphaeroidesRoleSigma FactorSinglet OxygenSiteSolar EnergySuperoxidesTestingTherapeuticTranscriptional RegulationZincantimicrobialbiological adaptation to stressbiological systemscancer cellcell killingchemical propertyin vivokillingsmemberphotosynthetic bacteriapreventresearch studyresponse
项目摘要
DESCRIPTION (provided by applicant): Molecular oxygen (O2) is critical to life on this planet; it is a product of oxygenic photosynthesis and it is a substrate for bioenergetic pathways like aerobic respiration. While O2 is relatively inert, it is converted to different chemical classes of toxic reactive oxygen species by either one electron transfer or energy transfer reactions. When single electrons are transferred to O2, it is reduced to superoxide, hydrogen peroxide, or hydroxyl radicals. When energy is transferred to O2, singlet oxygen ([1]O2) is formed. We have considerable information about how cells respond to superoxide, hydrogen peroxide and hydroxyl radicals. However, relatively little is known about how cells respond to [1]O2, a common reactive oxygen species that can destroy the integrity of bioenergetic membranes, damage many biomolecules, generate mutations, or kill cells. To rectify this situation, we will study the bacterial response to [1]O2. Our experiments capitalize on what is known about the formation and response to conditions that generate [1]O2 in the alpha-proteobacterium Rhodobacter sphaeroides. This is the biological system of choice for studying this response since photosynthetic organisms like R. sphaeroides generate significant amounts of [1]O2 as a byproduct of solar energy capture. In addition, we have identified a transcriptional response to conditions that generate [1]O2 in this bacterium. This transcriptional response to [1]O2 depends on an alternative sigma factor in the extracytoplasmic function family, sigmaE, and the anti-sigma factor, ChrR. We have also obtained a 3-dimensional view of the sigmaE-ChrR complex that controls the transcriptional response to [1]O2. In this project, we will determine how the presence of [1]O2 increases sigmaE activity. [1]O2 is bacteriocidal to cells lacking sigmaE, so we will also identify gene products that protect cells from this toxic reactive oxygen species. The chemical properties of [1]O2 predict that the damage generated by this reactive oxygen species and the activities that function in this stress response will differ from those produced in the presence of superoxide, hydrogen peroxide or hydroxyl radicals. Analysis of microbial genome sequences indicates that homologs of R. sphaeroides sigmaE and ChrR are present in many photosynthetic bacteria plus non-photosynthetic bacteria that are likely to encounter [1]O2 generated by other pathways as part of plant and animal defenses against pathogenic microbes. Thus, our research will answer important questions about the ability of many cells to sense and protect themselves from [1]O2 and the nature of the modifications caused by [1]O2 to proteins and other biomolecules. The use of [1]O2 by eukaryotic cells to defend against pathogenic microbes and in photodynamic therapy to kill cancer cells predicts that our findings will have large antimicrobial and therapeutic potential.
描述(由申请人提供):分子氧(O2)对地球上的生命至关重要;它是含氧光合作用的产物,是有氧呼吸等生物能量途径的底物。虽然O2是相对惰性的,但它可以通过单电子转移或能量转移反应转化为不同化学类别的有毒活性氧。当单个电子转移到O2上时,它被还原成超氧化物、过氧化氢或羟基自由基。当能量转移到O2时,形成单线态氧([1]O2)。关于细胞如何对超氧化物、过氧化氢和羟基自由基作出反应,我们有相当多的信息。然而,对于细胞如何对[1]O2作出反应,人们知之甚少。[1]O2是一种常见的活性氧,可以破坏生物能膜的完整性,破坏许多生物分子,产生突变或杀死细胞。为了纠正这种情况,我们将研究细菌对[1]O2的反应。我们的实验利用了α -变形杆菌球形红杆菌对产生[1]O2的条件的形成和反应。这是研究这种反应的首选生物系统,因为像r.s hahaeroides这样的光合生物会产生大量的[1]O2作为太阳能捕获的副产品。此外,我们已经确定了在这种细菌中产生[1]O2条件的转录反应。这种对[1]O2的转录反应取决于胞质外功能家族中的另一个sigma因子sigmaE和抗sigma因子ChrR。我们还获得了控制[1]O2转录反应的sigmaE-ChrR复合体的三维视图。在这个项目中,我们将确定bbbo2的存在是如何增加sigmaE活性的。[1]O2对缺乏sigmaE的细胞具有杀菌作用,因此我们也将鉴定保护细胞免受这种有毒活性氧伤害的基因产物。[1]O2的化学性质预示着这种活性氧产生的损伤和在这种应激反应中起作用的活性将不同于在超氧化物、过氧化氢或羟基自由基存在下产生的损伤。微生物基因组序列分析表明,sphaeroides sigmaE和ChrR的同源物存在于许多光合细菌和非光合细菌中,这些细菌可能会遇到其他途径产生的[1]O2,这是动植物防御病原微生物的一部分。因此,我们的研究将回答关于许多细胞感知和保护自己免受[1]O2的能力以及[1]O2对蛋白质和其他生物分子引起的修饰的性质的重要问题。真核细胞利用[1]O2抵御病原微生物和光动力疗法杀死癌细胞预示着我们的发现将具有巨大的抗菌和治疗潜力。
项目成果
期刊论文数量(11)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Conservation of thiol-oxidative stress responses regulated by SigR orthologues in actinomycetes.
- DOI:10.1111/j.1365-2958.2012.08115.x
- 发表时间:2012-07
- 期刊:
- 影响因子:3.6
- 作者:Kim MS;Dufour YS;Yoo JS;Cho YB;Park JH;Nam GB;Kim HM;Lee KL;Donohue TJ;Roe JH
- 通讯作者:Roe JH
Targeted sigma factor turnover inserts negative control into a positive feedback loop.
- DOI:10.1111/j.1365-2958.2009.06823.x
- 发表时间:2009-09
- 期刊:
- 影响因子:3.6
- 作者:Donohue TJ
- 通讯作者:Donohue TJ
Proteins needed to activate a transcriptional response to the reactive oxygen species singlet oxygen.
- DOI:10.1128/mbio.00541-12
- 发表时间:2013-01-08
- 期刊:
- 影响因子:6.4
- 作者:Nam TW;Ziegelhoffer EC;Lemke RA;Donohue TJ
- 通讯作者:Donohue TJ
Bacterial responses to photo-oxidative stress.
- DOI:10.1038/nrmicro2237
- 发表时间:2009-12
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
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{{ truncateString('TIMOTHY J DONOHUE', 18)}}的其他基金
2012 Microbial Stress Response Gordon Research Conference
2012 微生物应激反应戈登研究会议
- 批准号:
8305893 - 财政年份:2012
- 资助金额:
$ 26.54万 - 项目类别:
FORMALDEHYDE METABOLISM IN PURPLE NON SULPHUR BACTERIUM RHODOBACTER SPHAEROIDES
紫色非硫球红细菌中的甲醛代谢
- 批准号:
6309148 - 财政年份:2000
- 资助金额:
$ 26.54万 - 项目类别:
FORMALDEHYDE METABOLISM IN PURPLE NON SULPHUR BACTERIUM RHODOBACTER SPHAEROIDES
紫色非硫球红细菌中的甲醛代谢
- 批准号:
6298145 - 财政年份:1999
- 资助金额:
$ 26.54万 - 项目类别:
FORMALDEHYDE METABOLISM IN PURPLE NON SULPHUR BACTERIUM RHODOBACTER SPHAEROIDES
紫色非硫球红细菌中的甲醛代谢
- 批准号:
6281540 - 财政年份:1998
- 资助金额:
$ 26.54万 - 项目类别:
FORMALDEHYDE METABOLISM IN PURPLE NON SULPHUR BACTERIUM RHODOBACTER SPHAEROIDES
紫色非硫球红细菌中的甲醛代谢
- 批准号:
6252059 - 财政年份:1997
- 资助金额:
$ 26.54万 - 项目类别:
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