Analysis of the DksA regulon in the Lyme disease spirochete
莱姆病螺旋体中 DksA 调节子的分析
基本信息
- 批准号:10375559
- 负责人:
- 金额:$ 18.69万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-03-19 至 2024-02-29
- 项目状态:已结题
- 来源:
- 关键词:AddressAnimalsBacteriaBindingBinding ProteinsBorrelia burgdorferiComplementComplexDNA-Directed RNA PolymeraseDataDevelopmentDiseaseEnvironmentEtiologyGene ExpressionGenesGeneticGenetic TranscriptionGoalsGrowthIn VitroInfectionInterruptionInterventionIxodesKnowledgeLeadLife Cycle StagesLyme DiseaseMammalsMediatingMetabolic stressModalityMolecularMusNatureNucleotidesPathogenicityPhasePhysiologicalPlayProteomeRegulationRegulonRoleStressTicksTranslationsUnited StatesVector-transmitted infectious diseaseVirulenceWorkarthropod-bornebacterial fitnessdisorder preventionenvironmental adaptationenzooticexpectationgenetic approachgenetic regulatory proteinhuman diseasein vivoinnovationinsightmetabolomemutantnovelnutrient deprivationpreventresponsetranscriptometransmission processvector tick
项目摘要
ABSTRACT
Stringent response is a physiological mechanism utilized by bacteria to adapt to nutrient deprivation and many
other stresses. In Borrelia burgdorferi (Bb), the etiological agent of Lyme disease, stringent response is mediated
by both the alarmone nucleotides (p)ppGpp and the RNA polymerase-binding protein DksA. Recently, we found
that DksA plays an essential role in regulating Bb's virulence. First, dksA is highly expressed in infected animals
and is required by Bb to infect the mammalian hosts. Second, DksA is critical for Bb's optimal growth. Third,
DksA is required by Bb to cope with metabolic stress. Finally, in addition to function as a stringent response
regulator, DksA promotes the transcription and/or translation of genes contributing to Bb's survival in the host.
These combined data give rise to our hypothesis that DksA is a master regulator governing Bb's virulence gene
expression. This hypothesis will be addressed in two Specific Aims. In Aim 1 of this proposal, we will determine
the contribution of DksA to Bb's survival and persistence in ticks. In Aim 2, we will identify genes regulated by
DksA under various in vitro and in vivo conditions. These combined studies will (i) define the entire DksA regulon;
and (ii) provide a transformative understanding of the in vivo importance of DksA and the regulon. Resultant
findings could lead to the development of new strategies to prevent and/or treat Lyme disease.
摘要
严格反应是细菌用来适应营养缺乏和许多
其他压力。在莱姆病的病原体伯氏疏螺旋体(BB)中,严格的反应是介导的
由丙稀酮核苷酸(P)ppGpp和RNA聚合酶结合蛋白DksA共同作用。最近,我们发现
Dks A在调节BB的毒力方面起着重要作用。首先,dks A在受感染的动物中高度表达
并且是BB感染哺乳动物宿主所必需的。其次,Dks A对BB的最佳增长至关重要。第三,
BB需要Dks A来应对代谢应激。最后,除了起到严格应对的作用
作为调节因子,DksA促进有助于BB在宿主中生存的基因的转录和/或翻译。
这些数据结合在一起,提出了我们的假设,即DksA是控制BB毒力基因的主调控因子
表情。这一假设将在两个具体目标中得到解决。在本提案的目标1中,我们将确定
Dks A对Bb在硬蜱体内的存活和持久性的贡献。在目标2中,我们将识别受
在不同的体外和体内条件下,Dks A。这些联合研究将(I)确定整个Dks A调节子;
以及(Ii)提供对Dks A和调节子在体内的重要性的变革性理解。由此产生的
这些发现可能会导致开发新的策略来预防和/或治疗莱姆病。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
BB0761, a MepM homolog, contributes to Borrelia burgdorferi cell division and mammalian infectivity.
MEPM同源物BB0761为Borrelia Burgdorferi细胞分裂和哺乳动物感染力做出了贡献。
- DOI:10.1111/mmi.14916
- 发表时间:2022-06
- 期刊:
- 影响因子:3.6
- 作者:Thompson, Christina;George, Sierra;White, Maria L.;Eswara, Prahathees J.;Ouyang, Zhiming
- 通讯作者:Ouyang, Zhiming
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Zhiming Ouyang其他文献
Zhiming Ouyang的其他文献
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{{ truncateString('Zhiming Ouyang', 18)}}的其他基金
Analysis of the DksA regulon in the Lyme disease spirochete
莱姆病螺旋体中 DksA 调节子的分析
- 批准号:
10189812 - 财政年份:2021
- 资助金额:
$ 18.69万 - 项目类别:
Virulence regulation by BadR in the Lyme disease spirochete
BadR 对莱姆病螺旋体的毒力调节
- 批准号:
10210818 - 财政年份:2021
- 资助金额:
$ 18.69万 - 项目类别:
Virulence regulation by BadR in the Lyme disease spirochete
BadR 对莱姆病螺旋体的毒力调节
- 批准号:
10571907 - 财政年份:2021
- 资助金额:
$ 18.69万 - 项目类别:
Virulence regulation by BadR in the Lyme disease spirochete
BadR 对莱姆病螺旋体的毒力调节
- 批准号:
10376875 - 财政年份:2021
- 资助金额:
$ 18.69万 - 项目类别:
Virulence-associated genes in the Lyme disease spirochete
莱姆病螺旋体中的毒力相关基因
- 批准号:
9805771 - 财政年份:2019
- 资助金额:
$ 18.69万 - 项目类别:
Rrp2, an atypical bacterial enhancer binding protein in Borrelia burgdorferi
Rrp2,伯氏疏螺旋体中的非典型细菌增强子结合蛋白
- 批准号:
9103495 - 财政年份:2016
- 资助金额:
$ 18.69万 - 项目类别:
Rrp2, an atypical bacterial enhancer binding protein in Borrelia burgdorferi
Rrp2,伯氏疏螺旋体中的非典型细菌增强子结合蛋白
- 批准号:
9230812 - 财政年份:2016
- 资助金额:
$ 18.69万 - 项目类别:
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