Streptococcal secretion of pyruvate - a novel antioxidant strategy in the oral biofilm
链球菌分泌丙酮酸——口腔生物膜中的一种新型抗氧化策略
基本信息
- 批准号:10264935
- 负责人:
- 金额:$ 19.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-16 至 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcetatesAnaerobic BacteriaAntioxidantsApoptosisAreaBiological AssayCarbonCarbon DioxideCell SurvivalCell physiologyChIP-seqClinicalCommunitiesCompetitive BehaviorDental cariesDevelopmentDiffuseDiseaseDrug Metabolic DetoxicationEcologyEligibility DeterminationEnzymesEquilibriumEukaryotic CellGene Expression RegulationGeneticGenetic ScreeningGrowthHomeostasisHydrogen PeroxideKnowledgeMembraneMetabolicMetabolismMicrobial BiofilmsMinorMolecularMutagenesisOralOral cavityOral healthOxidative StressPathway interactionsPeriodontal DiseasesPeroxidasesPlayProcessProductionProkaryotic CellsPyruvatePyruvate OxidaseRegulationReportingRepressionRoleStreptococcusStressTranscriptalkyl hydroperoxide reductaseantimicrobial drugbasebiological adaptation to stresscatalasedisorder preventiondysbiosisextracellulargenetic manipulationimprovedmicrobialmicrobiome componentsnoveloral biofilmoral commensaloral microbiomeoral streptococcipathobiontpolymicrobial biofilmpublic health relevancetranscriptomics
项目摘要
Project Summary
Commensal streptococci play an important role in oral biofilm homeostasis. Disturbance of biofilm
homeostasis leads to dysbiosis and eventually disease development, including caries and
periodontal disease. Several oral streptococci are producing significant amounts of H2O2 able to
inhibit susceptible pathobionts involved in disease development. However, the production of H2O2
does not always correlate with the antagonistic ability of the producer. Our group recently
identified the mechanism behind this observation: oral streptococci secrete the central metabolite
pyruvate as potent H2O2 scavenger. The mechanism of pyruvate secretion as oxidative stress
response has been reported for eukaryotic cells, but has not been investigated in prokaryotes and
little is known about prokaryotic pyruvate transport in general. Our observation raises key
ecological questions about the role of commensal streptococci in the oral cavity: why do some
streptococcal H2O2 producers secrete protective amounts of pyruvate and others do not? What is
the genetic basis for this ability? What are the implications for oral health? The following specific
aims are proposed to identify and characterize the pyruvate secretion mechanism and its genetic
control in oral streptococci:
Aim I: Identify the pyruvate secretion mechanism and its specific regulation. We will identify
the genetic components required for pyruvate secretion by combining transposon mutagenesis
with an established genetic screening protocol. The regulation of these genes will be compared
between species. Aim I will determine how different streptococci modulate the H2O2/pyruvate
balance that is critical for oral microbial ecology.
Aim II: Characterize the regulatory network that determines the H2O2/pyruvate balance. We
will perform ChIP-seq (CCR+/-) under conditions of low and high pyruvate secretion to identify
the key regulatory components of this pathway. This will also serve as independent approach to
identify the pyruvate secretion mechanism.
An improved understanding of how the streptococcal community regulates its H2O2/pyruvate
balance will help to define the molecular determinates of disease development and provide a
novel target for disease prevention.
项目摘要
共生链球菌在口腔生物膜动态平衡中起着重要作用。生物膜的干扰
动态平衡导致生物失调,最终导致疾病发展,包括龋齿和
牙周病。几种口腔链球菌产生大量的过氧化氢,能够
抑制参与疾病发展的易感病原体。然而,过氧化氢的产生
并不总是与制作人的对抗能力相关。我们的小组最近
确定了这一观察背后的机制:口腔链球菌分泌中枢代谢物
丙酮酸是一种有效的过氧化氢清除剂。丙酮酸分泌作为氧化应激的机制
已经报道了真核细胞的反应,但还没有在原核生物和
人们对原核生物丙酮酸转运知之甚少。我们的观察提出了关键
口腔共生链球菌作用的生态学问题:为什么会有一些
链球菌产过氧化氢能分泌保护量的丙酮酸,而其他产生者不能吗?是什么
这种能力的遗传基础是什么?这对口腔健康有什么影响?以下是具体的
目的是鉴定和表征丙酮酸的分泌机制及其遗传
口腔链球菌的控制:
目的I:明确丙酮酸的分泌机制及其特异性调节。我们将确定
转座子联合诱变分泌丙酮酸所需的遗传成分
有一套既定的基因筛查方案。我们将比较这些基因的调控情况。
在物种之间。目的研究不同链球菌对过氧化氢/丙酮酸的调节作用。
对口腔微生物生态至关重要的平衡。
目的II:描述决定过氧化氢/丙酮酸平衡的调控网络。我们
将在低丙酮酸分泌和高丙酮酸分泌条件下进行CHIP-SEQ(Ccr+/-)鉴定
这一途径的关键调控成分。这也将作为独立的方法来实现
确定丙酮酸的分泌机制。
更好地理解链球菌群落如何调节其过氧化氢/丙酮酸
BALANCE将有助于定义疾病发展的分子决定因素并提供
疾病预防的新目标。
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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Jens Kreth其他文献
Jens Kreth的其他文献
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{{ truncateString('Jens Kreth', 18)}}的其他基金
Pyruvate oxidase: a molecular determinant of commensalism among the oral microbiome
丙酮酸氧化酶:口腔微生物群共生的分子决定因素
- 批准号:
10589019 - 财政年份:2020
- 资助金额:
$ 19.25万 - 项目类别:
Pyruvate oxidase: a molecular determinant of commensalism among the oral microbiome
丙酮酸氧化酶:口腔微生物群共生的分子决定因素
- 批准号:
10362734 - 财政年份:2020
- 资助金额:
$ 19.25万 - 项目类别:
Pyruvate oxidase determines ecological fitness of oral streptococci
丙酮酸氧化酶决定口腔链球菌的生态适应性
- 批准号:
8819119 - 财政年份:2014
- 资助金额:
$ 19.25万 - 项目类别:
Pyruvate oxidase determines ecological fitness of oral streptococci
丙酮酸氧化酶决定口腔链球菌的生态适应性
- 批准号:
8631680 - 财政年份:2014
- 资助金额:
$ 19.25万 - 项目类别:
Pyruvate oxidase determines ecological fitness of oral streptococci
丙酮酸氧化酶决定口腔链球菌的生态适应性
- 批准号:
9001970 - 财政年份:2014
- 资助金额:
$ 19.25万 - 项目类别:
Pyruvate oxidase determines ecological fitness of oral streptococci
丙酮酸氧化酶决定口腔链球菌的生态适应性
- 批准号:
9221999 - 财政年份:2014
- 资助金额:
$ 19.25万 - 项目类别:
Ser/Thr protein kinase PknB as target to decrease Streptococcus mutans ecological
Ser/Thr 蛋白激酶 PknB 作为减少变形链球菌生态的靶点
- 批准号:
8283716 - 财政年份:2012
- 资助金额:
$ 19.25万 - 项目类别:
Ser/Thr protein kinase PknB as target to decrease Streptococcus mutans ecological
Ser/Thr 蛋白激酶 PknB 作为减少变形链球菌生态的靶点
- 批准号:
8513966 - 财政年份:2012
- 资助金额:
$ 19.25万 - 项目类别:
Interspecies Streptococcal Antagonisms in Oral Biofilms
口腔生物膜中的种间链球菌拮抗作用
- 批准号:
8015639 - 财政年份:2009
- 资助金额:
$ 19.25万 - 项目类别:
Interspecies Streptococcal Antagonisms in Oral Biofilms
口腔生物膜中的种间链球菌拮抗作用
- 批准号:
7750387 - 财政年份:2009
- 资助金额:
$ 19.25万 - 项目类别:
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