Cyclic di-GMP Second Messenger Signaling in the Tickborne Relapsing Fever Spirochete, Borrelia turicatae
蜱传回归热螺旋体、Borrelia turicatae 中的环状 di-GMP 第二信使信号传导
基本信息
- 批准号:10378138
- 负责人:
- 金额:$ 22.43万
- 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:2021-03-25 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:AddressAntimicrobial ResistanceApplications GrantsAreaArgasidaeArthropod VectorsArthropodsBacteriaBiologyBorreliaBorrelia burgdorferiBorrelia turicataeCell physiologyChemotaxisDefectDeveloping CountriesDiagnosticDigestionDinucleoside PhosphatesEnvironmentEtiologyFutureGelGel ChromatographyGene ExpressionGene ProteinsGlobal ChangeGuanosine MonophosphateHeavy MetalsHigh-Throughput Nucleotide SequencingHumanHuman bodyIndividualInfectionIxodesKnowledgeLeadLiquid ChromatographyLyme DiseaseMeasuresMediatingMicrobial BiofilmsModelingMolecularMusOrder SpirochaetalesOrnithodorosPathogenesisPathogenicityPatternPediculus humanus humanusPeriodicityPhenotypePhotosynthesisPlayProcessProductionProteomeRegulationRegulonRelapsing FeverRoleSecond Messenger SystemsSignal PathwaySignal TransductionSpirochaetales InfectionsSystemTestingTherapeutic InterventionTick-Borne Relapsing FeverTicksVirulenceVirulence FactorsVirulentWorkbacterial metabolismcDNA Librarycell motilitydefined contributiondimerenvironmental adaptationenzooticinsightmutantneglectpathogenprotein expressionrelapsing fever borreliasmall moleculetandem mass spectrometrytranscriptometranscriptome sequencingtransmission processvectorvector-borne
项目摘要
PROJECT SUMMARY/ABSTRACT
The vector-borne spirochetes that cause relapsing fever are transmitted to humans by either ticks or human
body lice. Despite identification of the etiological agents of relapsing fever over 100 years ago, very little
information exists regarding their pathogenesis of these bacteria. Relapsing fever is more common in developing
countries, but tickborne relapsing fever (TBRF) also occurs in areas of the U.S. where Ixodes and Ornithodoros
species of ticks, the vectors for TBRF spirochetes, are endemic. During their natural enzootic cycle, vector-borne
spirochetes exist in two distinct niches found within the arthropod vector and the vertebrate. It is well
established that Lyme disease spirochetes must undergo significant changes in global gene expression to allow
them to adapt to these two diverse environments. Cyclic dimeric guanosine monophosphate (c-di-GMP) is an
important second messenger molecule that plays a key role during the enzootic cycle of Borrelia burgdorferi,
but its regulatory contribution in TBRF spirochetes has not been investigated. In this proposal, we will test the
role of the c-di-GMP signaling pathway in promoting adaptation of TBRF spirochetes to the different host
environments encountered during the bacterial natural lifecycle. While we expect c-di-GMP-dependent
signaling to be important for the enzootic cycle of TBRF spirochetes, there are also significant differences
between the pathogenesis and vector biology of Lyme disease Borrelia and TBRF Borrelia that lead us to
anticipate that the relative contribution of c-di-GMP during TBRF spirochete infection and vector colonization
could be unique. To being addressing this, we have inactivated individual components in the c-di-GMP
regulatory system in a low-passage, virulent isolate of B. turicatae. In Specific Aim 1, the phenotypes of these
mutants will be evaluated using the experimental B. turicatae-O. turicata transmission/infection model to define
the importance of the c-di-GMP signaling pathway during the enzootic cycle of B. turicatae. In Specific Aim 2,
we will use these mutants to determine the influence of the c-di-GMP signaling system on B. turicatae global
gene expression and protein production. These aims will provide critical knowledge regarding the regulatory
networks that control B. turicatae adaptation during transmission and infection. Molecular characterization of
the individual c-di-GMP signaling components, their specific roles in virulence regulation, and potential
virulence determinants will be the focus of future R01 grant proposals. Regulators and virulence factors
identified in this project represent potential targets against which future therapeutic interventions and/or
diagnostics for TBRF could be developed.
项目总结/文摘
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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Jon Scott Blevins其他文献
Jon Scott Blevins的其他文献
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{{ truncateString('Jon Scott Blevins', 18)}}的其他基金
Cyclic di-AMP-dependent signaling in tickborne relapsing fever Borrelia
蜱传回归热伯氏疏螺旋体中的环状双 AMP 依赖性信号传导
- 批准号:
10679004 - 财政年份:2022
- 资助金额:
$ 22.43万 - 项目类别:
Cyclic di-AMP-dependent signaling in tickborne relapsing fever Borrelia
蜱传回归热伯氏疏螺旋体中的环状双 AMP 依赖性信号传导
- 批准号:
10503309 - 财政年份:2022
- 资助金额:
$ 22.43万 - 项目类别:
Rrp2-dependent gene regulation in Borrelia burgdorferi
伯氏疏螺旋体中 Rrp2 依赖性基因调控
- 批准号:
9090056 - 财政年份:2015
- 资助金额:
$ 22.43万 - 项目类别:
Rrp2-dependent gene regulation in Borrelia burgdorferi
伯氏疏螺旋体中 Rrp2 依赖性基因调控
- 批准号:
8951367 - 财政年份:2015
- 资助金额:
$ 22.43万 - 项目类别:
RpoS-mediated virulence regulation in Borrelia burgdorferi
RpoS 介导的伯氏疏螺旋体毒力调控
- 批准号:
8722793 - 财政年份:2013
- 资助金额:
$ 22.43万 - 项目类别:
RpoS-mediated virulence regulation in Borrelia burgdorferi
RpoS 介导的伯氏疏螺旋体毒力调控
- 批准号:
7992838 - 财政年份:2010
- 资助金额:
$ 22.43万 - 项目类别:
RpoS-mediated virulence regulation in Borrelia burgdorferi
RpoS 介导的伯氏疏螺旋体毒力调控
- 批准号:
8259762 - 财政年份:2010
- 资助金额:
$ 22.43万 - 项目类别:
RpoS-mediated virulence regulation in Borrelia burgdorferi
RpoS 介导的伯氏疏螺旋体毒力调控
- 批准号:
8449257 - 财政年份:2010
- 资助金额:
$ 22.43万 - 项目类别:
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