Legionella pneumophila developmental cycle & virulence
嗜肺军团菌发育周期
基本信息
- 批准号:7330345
- 负责人:
- 金额:$ 37.02万
- 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:2006-12-15 至 2011-11-30
- 项目状态:已结题
- 来源:
- 关键词:A/J MouseAcuteAcute PneumoniaAerosolsAmoeba genusAnimal ModelAntibioticsBacteriaBiochemicalBiocideBiological AssayBiologyBurkholderiaCatalogingCatalogsCell membraneCellsCollaborationsConditionCoxiellaCystDefectDetectionDetergentsDevelopmentDiseaseEarly EndosomeElderlyElectron MicroscopyEnvironmentEnvironmental Risk FactorFractionationGelGene ExpressionGene FusionGenesGenus MycobacteriumGoalsGreen Fluorescent ProteinsGrowthHabitatsHealthHealth HazardsHeatingHela CellsHumanImmunocompromised HostIn VitroInfectionInvadedKnowledgeL FormsLeadLegionella pneumophilaLegionnaires&apos DiseaseLethal Dose 50LettersLightLungMeasuresMembraneModelingMorphogenesisMutationNatural ImmunityParasitesPathogenesisPathologyPeroxidesPersonsPhysiologic pulsePneumoniaPolymerase Chain ReactionProductionProteinsProteomeProtocols documentationProtozoaPulse takingRadiolabeledRangeRegulator GenesReporterResearchResearch PersonnelResistanceRiskRoleSimulateSourceStagingStaining methodStainsSuspension substanceSuspensionsTemperatureTestingTetrahymenaVirulenceVirulentWaterbasechlorinationdesigndisease transmissiongenetic analysishuman diseaseimprovedinsightmacrophagemicrobialmouse modelmutantnutritionpathogenperiplasmprogramsprotein functionprotein structureradiotracerresiliencetraffickingtransmission process
项目摘要
Legionella pneumophila (L. pneumophila) resides in aquatic habitats as an intracellular parasite of protozoa
and when transmitted in aerosols to susceptible humans, produces an acute pneumonia known as
Legionnaires' disease. Transmission of this disease is always one-way - from the environment to humans,
and despite 30 years of research, an explanation for why this disease is not spread from person to person
has not been offered. We have documented a developmental cycle in cell based infection models in which
vegetative bacteria differentiate into cyst-like metabolically dormant forms that are resilient and highly
infectious. These cysts are resistant to the effects of antibiotics, detergents and other toxic agents and can
persist in water sources for extended periods where they present a health hazard. To determine if these
cysts are responsible for transmission of Legionnaires' disease we propose the following aims: 1) To develop
infection models in protozoa and in tap water to identify environmental conditions that promote cyst
morphogenesis with sub aims of (i) tracking morphogenesis by light and electron microscopy; (i) by reporter
gene fusions; (iii) pulse chase radiolabeling and proteome profiling and (iv)to assess cyst forms for
resilience to detergents, biocides, and antibiotics; and infectiousness for amoebae and A/J mouse
macrophages. 2) Assessment of virulence of cysts in an A/J mouse aerosol challenge model; and 3) To
characterize the cyst like forms arising from protozoa,water and HeLa cells by (i) 2D gel proteome profiling
for unique proteins, (ii)cyst fractionation studies to identify proteins of the outer membrane, periplasm and
cytoplasmic membrane and (iii) use a mutation based approach to study developmentally regulated genes
and regulatory factors. We anticipate that continued study of the planktonic cysts will contribute significant
new knowledge to our understanding of the biology, pathogenesis, persistence and transmission of
Legionnaires' disease. Relevance to human health. Legionnaires' disease is a rapidly growing health risk
world wide, and especially for the elderly and immunocompromised. The knowledge gained from these
studies should lead to improved detection and control measures that reduce the risk to humans. These
studies should also provide insights relevant to other opportunistic environmental pathogens including
oxiella, Burkholderia and species of Mycobacterium.
嗜肺军团菌(L. pneumophila)作为原生动物的细胞内寄生虫居住在水生生境中
当通过气溶胶传播给易感人群时,会产生一种急性肺炎,
军团病。这种疾病的传播总是单向的--从环境到人类,
尽管经过了30年的研究,
还没有被提供。我们已经在基于细胞的感染模型中记录了发育周期,其中
营养细菌分化成孢囊样的代谢休眠形式,
传染性这些囊肿对抗生素、清洁剂和其他有毒物质的作用有抵抗力,
长期存在于水源中,对健康构成危害。为了确定这些
囊肿是导致军团病传播的原因,我们提出以下目标:1)开发
原生动物和自来水中的感染模型,以确定促进包囊的环境条件
形态发生,子目标为(i)通过光学和电子显微镜跟踪形态发生;(i)通过报告基因
基因融合;(iii)脉冲追踪放射性标记和蛋白质组分析;以及(iv)评估
对清洁剂、杀菌剂和抗生素的耐受性;以及对阿米巴原虫和A/J小鼠的感染性
巨噬细胞2)在A/J小鼠气溶胶攻击模型中评估包囊的毒力;以及3)
通过(i)二维凝胶蛋白质组分析表征原生动物、水和HeLa细胞产生的囊样形式
对于独特的蛋白质,(ii)包囊分级分离研究,以鉴定外膜、周质和
细胞质膜和(iii)使用基于突变的方法来研究发育调控基因
和监管因素。我们预期,继续研究的前列腺囊肿将有助于显着
新的知识,我们的生物学,发病机制,持久性和传播的理解,
军团病。与人类健康的相关性。军团病是一种快速增长的健康风险
特别是对于老年人和免疫功能低下的人。从这些中获得的知识
研究应导致改进检测和控制措施,减少对人类的风险。这些
研究还应提供与其他机会性环境病原体相关的见解,
oxiella、Burkholderia和Mycobacterium种。
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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PAUL Stokes HOFFMAN其他文献
PAUL Stokes HOFFMAN的其他文献
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{{ truncateString('PAUL Stokes HOFFMAN', 18)}}的其他基金
PFOR inhibitor amixicile for treatment of drug resistant parasites and bacteria
PFOR 抑制剂 amixicile 用于治疗耐药寄生虫和细菌
- 批准号:
8700080 - 财政年份:2014
- 资助金额:
$ 37.02万 - 项目类别:
Nitrothiazolides:Broad-Spectrum Category B Anti-parasitic/bacterial Therapeutics
硝基噻唑类:广谱 B 类抗寄生虫/细菌治疗药物
- 批准号:
7886745 - 财政年份:2007
- 资助金额:
$ 37.02万 - 项目类别:
Helicobacter pylori: Tactic Responses and Persistence in the Gastric Mucosa
幽门螺杆菌:胃粘膜中的策略反应和持久性
- 批准号:
7567485 - 财政年份:2007
- 资助金额:
$ 37.02万 - 项目类别:
Nitrothiazolides:Broad-Spectrum Category B Anti-parasitic/bacterial Therapeutics
硝基噻唑类:广谱 B 类抗寄生虫/细菌治疗药物
- 批准号:
7669129 - 财政年份:2007
- 资助金额:
$ 37.02万 - 项目类别:
Helicobacter pylori: Tactic Responses and Persistence in the Gastric Mucosa
幽门螺杆菌:胃粘膜中的策略反应和持久性
- 批准号:
8035489 - 财政年份:2007
- 资助金额:
$ 37.02万 - 项目类别:
Nitrothiazolides:Broad-Spectrum Category B Anti-parasitic/bacterial Therapeutics
硝基噻唑类:广谱 B 类抗寄生虫/细菌治疗药物
- 批准号:
7325362 - 财政年份:2007
- 资助金额:
$ 37.02万 - 项目类别:
Nitrothiazolides:Broad-Spectrum Category B Anti-parasitic/bacterial Therapeutics
硝基噻唑类:广谱 B 类抗寄生虫/细菌治疗药物
- 批准号:
8115981 - 财政年份:2007
- 资助金额:
$ 37.02万 - 项目类别:
Helicobacter pylori: Tactic Responses and Persistence in the Gastric Mucosa
幽门螺杆菌:胃粘膜中的策略反应和持久性
- 批准号:
7364652 - 财政年份:2007
- 资助金额:
$ 37.02万 - 项目类别:
Helicobacter pylori: Tactic Responses and Persistence in the Gastric Mucosa
幽门螺杆菌:胃粘膜中的策略反应和持久性
- 批准号:
7264446 - 财政年份:2007
- 资助金额:
$ 37.02万 - 项目类别:
Nitrothiazolides:Broad-Spectrum Category B Anti-parasitic/bacterial Therapeutics
硝基噻唑类:广谱 B 类抗寄生虫/细菌治疗药物
- 批准号:
7471459 - 财政年份:2007
- 资助金额:
$ 37.02万 - 项目类别:
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