Virulence of the Opportunistic Pathogen Rhodococcis Equi
机会性病原体马红球菌的毒力
基本信息
- 批准号:7343180
- 负责人:
- 金额:$ 31.55万
- 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:2006-02-01 至 2011-01-31
- 项目状态:已结题
- 来源:
- 关键词:Actinobacteria classActinomycesAddressAffectAttenuatedBacteriaBindingBinding SitesBiological AssayBiologyBreathingCellular biologyClinicalComplexDataDefectDevelopmentDiseaseDisruptionEpidemicEventGene FamilyGenesGeneticGoalsGranulomatousGrowthHIVHigh temperature of physical objectHomologous GeneHost DefenseImmunityIn VitroIndividualInfectionInflammationInvestigationIonsKnowledgeLifeLightLipoproteinsLocationLysosomesMacrophage Cell BiologyMalignant NeoplasmsMethodsMolecularMolecular Mechanisms of ActionMonitorMusMutagenesisMycobacterium tuberculosisNatureObstructionOxidative StressPathogenesisPathway interactionsPersonsPhagocytosisPhagosomesPhenotypePhysiologyPlasmidsPneumoniaPositioning AttributeProcessProductionProteinsRecombinantsRegulationRegulatory PathwayRegulonReporterResearchResearch PersonnelResourcesRhodococcus equiRoleSignal TransductionSoilStimulusSumSurfaceSystemTemperatureTestingTimeVirulenceWorkattenuationbasechemotherapyexpectationgenetic analysisgenetic manipulationin vivoinnovationinsightintracellular parasitismkillingsmacrophagemembermortalitymouse modelmutantnovelpathogenprogramspromoterresistance factorsresponsetooltrafficking
项目摘要
With the arrival of the HIV epidemic and the increase in individuals undergoing chemotherapy for various
cancers, the understudied zoonotic opportunistic pathogen Rhodococcus equi has emerged as cause of life-
threatening pneumonia in persons of compromised immunity. Rhodococcal pneumonia is characterized by
pyogranulomatous inflammation with cavitation, which can be misdiagnosed as Mycobacterium tuberculosis
infection. R. equi is a common soil-borne facultative actinomycete which, when inhaled, resists innate killing
mechanisms and readily multiplies in macrophages of susceptible hosts, likely by perturbation of endosomal
trafficking. Little is known about the molecular basis for R. equi pathogenesis, and prior to our recent work,
few tools existed to allow a thorough genetic analysis of this bacterium. Recently, we have developed the
genetic methods to construct defined mutants of R. equi and have also created an efficient transposon
mutagenesis system. Using these new tools, we demonstrated that vapA (virulence associated p/otein A), a
gene present on the virulence plasmid of R. equi, is required for intracellular growth and full virulence.
Deletion of vapA attenuates the bacterium, rendering it incapable of growth in vivo and unable to replicate in
macrophages cultured in vitro. Our long-term goal is to completely dissect the genetic basis for R. equi
virulence. We propose to do so by first expanding our understanding of vapA, which is to date the only
known R. equi virulence determinant. The first AIM of this work is to identify the mechanism of action of
vapA. To do so, we will define the intracellular events post phagocytosis of both wild type R. equi and the
vapA deletion mutant. Specifically we will characterize the process of phagosomal maturation in wild type R.
equi infected macrophages and test the influence of VapA on phagosome acidification and fusion with
lysosomes. We will identify interacting host protein partners of VapA. The second AIM is to characterize the
R. equi virulence regulon through the examination of regulators of vapA expression, VirR (yjrulence
regulator) and VarA (yap regulator). We will identify the specific signals transduced by these regulators and
identify additional genes controlled by them. We will establish the effects of deletion mutants of virR and
varA on R. equi virulence. Finally, we will identify the binding sites of the regulators to the vapA promoter.
These studies addressing the molecular mechanisms of R. equi pathogenesis will further our understanding
of macrophage cell biology and will yield insight into the biology of actinomycete host-pathogen relationships
in general.
随着艾滋病毒流行的到来和个体接受各种化疗的增加
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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MARY HONDALUS的其他文献
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{{ truncateString('MARY HONDALUS', 18)}}的其他基金
M. tuberculosis genes required for pulmonary survival revealed by TraCS
TraCS 揭示肺存活所需的结核分枝杆菌基因
- 批准号:
8386090 - 财政年份:2012
- 资助金额:
$ 31.55万 - 项目类别:
M. tuberculosis genes required for pulmonary survival revealed by TraCS
TraCS 揭示肺存活所需的结核分枝杆菌基因
- 批准号:
8463982 - 财政年份:2012
- 资助金额:
$ 31.55万 - 项目类别:
Virulence of the Opportunistic Pathogen Rhodococcis Equi
机会性病原体马红球菌的毒力
- 批准号:
7576142 - 财政年份:2006
- 资助金额:
$ 31.55万 - 项目类别:
Virulence of the Opportunistic Pathogen Rhodococcis Equi
机会性病原体马红球菌的毒力
- 批准号:
7758845 - 财政年份:2006
- 资助金额:
$ 31.55万 - 项目类别:
Virulence of the Opportunistic Pathogen Rhodococcis Equi
机会性病原体马红球菌的毒力
- 批准号:
7064408 - 财政年份:2006
- 资助金额:
$ 31.55万 - 项目类别:
Virulence of the opportunistic pathogen Rhodococcus equi
机会性病原体马红球菌的毒力
- 批准号:
7174191 - 财政年份:2006
- 资助金额:
$ 31.55万 - 项目类别:
MACROPHAGE RECONGNITION AND PHAGOCYTOSIS OF RHODOCOCCUS
红球菌的巨噬细胞识别和吞噬作用
- 批准号:
3085401 - 财政年份:1991
- 资助金额:
$ 31.55万 - 项目类别:
MACROPHAGE RECOGNITION AND PHAGOCYTOSIS OF RHODOCOCCUS
红球菌的巨噬细胞识别和吞噬作用
- 批准号:
3085403 - 财政年份:1991
- 资助金额:
$ 31.55万 - 项目类别:
MACROPHAGE RECOGNITION AND PHAGOCYTOSIS OF RHODOCOCCUS
红球菌的巨噬细胞识别和吞噬作用
- 批准号:
2057019 - 财政年份:1991
- 资助金额:
$ 31.55万 - 项目类别:
MACROPHAGE RECONGNITION AND PHAGOCYTOSIS OF RHODOCOCCUS
红球菌的巨噬细胞识别和吞噬作用
- 批准号:
3085402 - 财政年份:1991
- 资助金额:
$ 31.55万 - 项目类别:
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