The Role of YebC in persistent infection of the Lyme disease pathogen
YebC 在莱姆病病原体持续感染中的作用
基本信息
- 批准号:10527922
- 负责人:
- 金额:$ 19.81万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-05-16 至 2024-04-30
- 项目状态:已结题
- 来源:
- 关键词:Antibody TherapyAntigenic VariationBorreliaBorrelia burgdorferiDataDown-RegulationFill-ItGene ExpressionGenetic RecombinationGenetic TranscriptionGenomeGoalsHumoral ImmunitiesImmune EvasionImmune responseImmune signalingImmunocompetentIn VitroInfectionIsopropyl ThiogalactosideLipoproteinsLyme DiseaseMammalsMediatingMolecularMusOpen Reading FramesOspC proteinOutcomePatternPhaseProcessPublic HealthRegulationRoleSCID MiceSignal TransductionSurfaceSurface AntigensTestingUnited StatesUp-RegulationVirulenceWorkchronic infectiondifferential expressionexpectationimprovedmouse modelnovelpathogentherapeutic targettranscription factorvirtual
项目摘要
PROJECT ABSTRACT
Lyme disease has emerged as a major public health threat in the United States. One of the unique
features of the Lyme disease pathogen Borrelia (or Borreliella) burgdorferi (B. burgdorferi)
infection is its ability to evade immune responses and cause persistent infection in mammalian
hosts. Differential expression of surface antigens and VlsE antigen variation are two major
strategies evolved by B. burgdorferi to achieve persistence in mammals. During the transition from
early to persistent phase of infection when humoral immunity is activated, this spirochetal
pathogen downregulates OspC, a major surface antigen that is required for early phase of
infection. Concomitantly, B. burgdorferi upregulates VlsE, a surface lipoprotein that undergoes
antigen variation in mammalian hosts. How vlsE is differentially regulated and what controls vlsE
recombination are not unknown. We recently discovered a hypothetical ORF (BB0025) in the B.
burgdorferi genome, encoding a novel regulator YebC that controls vlsE expression. In this
application, we will test the hypothesis that YebC orchestrates differential expression of vlsE
during the early and persistent phases of infection (Aim 1). We will also examine whether
downregulation of ospC requires YebC during mammalian infection. In addition to regulating vlsE
expression, we provide preliminary data supporting the hypothesis that YebC is also involved in
regulating the process of vlsE recombination. This will be tested in Aim 2. Upon the successful
completion of this project, we will have identified a key regulator involving in vlsE regulation and
antigen variation. Not only will it fill a major gap in our understanding of how B. burgdorferi
upregulates vlsE expression and activate the vlsE recombination in the mammalian host, but also
will open up a new avenue for further elucidating how YebC responds to humoral immune
response or other host signals to regulates virulence gene expression. Thus, the outcome of this
application will significantly advance our understanding immune evasion and persistent infection
of B. burgdorferi and other pathogens in general.
项目摘要
莱姆病已成为美国的主要公共卫生威胁。独一无二的之一
莱姆病病原体伯氏疏螺旋体(Borrelia)(或伯氏疏螺旋体(Borreliella))的特征
感染是指其逃避免疫反应并导致哺乳动物持续感染的能力
主机。表面抗原差异表达和VlsE抗原变异是两个主要因素
伯氏疏螺旋体进化出的策略在哺乳动物中实现持久性。在过渡期间从
当体液免疫被激活时,感染的早期至持续阶段,这种螺旋体
病原体下调 OspC,这是早期阶段所需的主要表面抗原
感染。与此同时,伯氏疏螺旋体上调 VlsE,一种表面脂蛋白,
哺乳动物宿主中的抗原变异。 vlsE 的差异调节方式以及控制 vlsE 的因素
重组并非未知。我们最近在 B.
burgdorferi 基因组,编码控制 vlsE 表达的新型调节因子 YebC。在这个
应用程序中,我们将测试 YebC 协调 vlsE 差异表达的假设
在感染的早期和持续阶段(目标 1)。我们还将检查是否
在哺乳动物感染期间,ospC 的下调需要 YebC。除了调节 vlsE
表达,我们提供了初步数据支持 YebC 也参与的假设
调节 vlsE 重组过程。这将在目标 2 中进行测试。成功后
该项目完成后,我们将确定参与 vLSE 监管的关键监管机构
抗原变异。它不仅将填补我们对伯氏疏螺旋体如何理解的重大空白
上调 vlsE 表达并激活哺乳动物宿主中的 vlsE 重组,而且
将为进一步阐明 YebC 如何响应体液免疫开辟新途径
反应或其他宿主信号来调节毒力基因表达。因此,这次的结果
应用将显着增进我们对免疫逃避和持续感染的理解
伯氏疏螺旋体和其他一般病原体。
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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X. Frank Yang的其他文献
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{{ truncateString('X. Frank Yang', 18)}}的其他基金
The Role of YebC in persistent infection of the Lyme disease pathogen
YebC 在莱姆病病原体持续感染中的作用
- 批准号:
10622561 - 财政年份:2022
- 资助金额:
$ 19.81万 - 项目类别:
The mechanism of activation of the Rrp2-RpoN-RpoS pathway in Borrelia burgdorferi
伯氏疏螺旋体Rrp2-RpoN-RpoS通路的激活机制
- 批准号:
7773498 - 财政年份:2010
- 资助金额:
$ 19.81万 - 项目类别:
The mechanism of activation of the Rrp2-RpoN-RpoS pathway in Borrelia burgdorferi
伯氏疏螺旋体Rrp2-RpoN-RpoS通路的激活机制
- 批准号:
8073426 - 财政年份:2010
- 资助金额:
$ 19.81万 - 项目类别:
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