Coxiella survival mechanisms in the intracellular niche
细胞内生态位中的柯克斯体存活机制
基本信息
- 批准号:10375875
- 负责人:
- 金额:$ 58.34万
- 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:2022-07-13 至 2027-06-30
- 项目状态:未结题
- 来源:
- 关键词:AcuteAnimalsAntibiotic TherapyAntibioticsBacteriaBiogenesisBiologicalCarbon DioxideCatabolismCellsCharacteristicsChronicChronic DiseaseClinicalCoxiellaCoxiella burnetiiDataDesiccationDigestionDiseaseDisease OutbreaksEndocarditisEnzymesEpidemiologyExposure toFatigueGrowthHomeostasisHumanImmune responseIndividualInfectionKnowledgeLifeLysosomesMaintenanceMetabolicMetabolismModelingMolecularNetherlandsNutrientPathogenesisPathway interactionsPatient NoncompliancePatientsPeptide HydrolasesPhagocytesPhagolysosomePhosphoric Monoester HydrolasesProteinsQ FeverRegimenRegulationReplication InitiationReproduction sporesRoleStressTestingTranscriptional ActivationVacuoleVariantVirulenceZoonosesacid stressbasebiological adaptation to stresscarbonate dehydratasechronic infectionflugene networkhuman pathogenintracellular parasitismnew therapeutic targetnovelnovel therapeuticspH Homeostasispathogenpathogenic bacteriaresponsetherapeutic targettranscription factor
项目摘要
PROJECT SUMMARY/ABSTRACT
Coxiella burnetii is the causative agent of human Q fever, a zoonotic disease that can cause a debilitating, flu-
like illness in acute cases, or a life-threatening endocarditis in chronically infected patients. Q fever patients
present with few distinguishing clinical features, and chronic disease requires a minimum of 18 months of
antibiotic treatment, highlighting the need for new therapeutics. An obligate intracellular pathogen, Coxiella
survives inside a vacuole within infected cells that has characteristics of a functional phagolysosome, including
active proteases and phosphatases and moderately acidic pH, a physicochemical parameter to which C. burnetii
is exquisitely adapted. C. burnetii is a strict moderate acidophile capable of efficient nutrient transport, catabolism
and replication only within a narrow pH range under both host cell-free and intracellular conditions. The objective
of this application is to identify host and pathogen factors that function to maintain both CCV and bacterial
cytoplasmic pH. Aim 1 will test the hypothesis that C. burnetii controls bacterial cytoplasmic pH via carbonic
anhydrase-dependent metabolism of CO2 and also how the metabolically dormant Small Cell Variant of C.
burnetii protects the pathogen against acid stress. Aim 2 will test the hypothesis that C. burnetii regulates CCV
pH by manipulating host lysosomal biogenesis. Understanding the molecular mechanisms behind C. burnetii
survival within the acidic CCV will allow identification of potential therapeutic targets.
项目总结/摘要
贝氏柯克斯体是人类Q热的病原体,Q热是一种人畜共患疾病,可导致虚弱的流感,
如急性疾病,或慢性感染患者危及生命的心内膜炎。Q热患者
目前几乎没有明显的临床特征,慢性疾病需要至少18个月的治疗。
抗生素治疗,突出了对新疗法的需求。一种专性胞内病原体,柯克斯体
在感染细胞内的空泡内存活,具有功能性吞噬溶酶体的特征,包括
活性蛋白酶和磷酸酶以及中等酸性pH,这是C.贝氏
是非常适合的。C.贝氏菌是一种严格的中度嗜酸菌,能够有效地运输营养物质,
并且在无宿主细胞和细胞内条件下仅在窄pH范围内复制。客观
本申请的目的是鉴定起维持CCV和细菌CCV的作用的宿主和病原体因子。
目的1将检验C.伯氏菌通过碳调节细菌细胞质pH
脱水酶依赖的CO2代谢以及代谢休眠的C.
贝氏菌保护病原体免受酸胁迫。目标2将检验假设C.贝氏菌调节CCV
通过操纵宿主溶酶体生物发生来调节pH。了解C.贝氏
在酸性CCV中的存活将允许鉴定潜在的治疗靶点。
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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{{ truncateString('STACEY D GILK', 18)}}的其他基金
Coxiella survival mechanisms in the intracellular niche
细胞内生态位中的柯克斯体存活机制
- 批准号:
10664843 - 财政年份:2022
- 资助金额:
$ 58.34万 - 项目类别:
Coxiella survival mechanisms in the intracellular niche
细胞内生态位中的柯克斯体存活机制
- 批准号:
10797442 - 财政年份:2022
- 资助金额:
$ 58.34万 - 项目类别:
Coxiella secreted proteins mediating inter-organelle membrane contact sites
柯克斯体分泌的蛋白质介导细胞器间膜接触位点
- 批准号:
10575434 - 财政年份:2022
- 资助金额:
$ 58.34万 - 项目类别:
Intracellular IL-17 signaling during Coxiella burnetii infection
伯氏柯克斯体感染过程中细胞内 IL-17 信号转导
- 批准号:
10201507 - 财政年份:2020
- 资助金额:
$ 58.34万 - 项目类别:
Intracellular IL-17 signaling during Coxiella burnetii infection
伯氏柯克斯体感染过程中细胞内 IL-17 信号转导
- 批准号:
10295139 - 财政年份:2020
- 资助金额:
$ 58.34万 - 项目类别:
Intracellular IL-17 signaling during Coxiella burnetii infection
伯氏柯克斯体感染过程中细胞内 IL-17 信号转导
- 批准号:
10063664 - 财政年份:2020
- 资助金额:
$ 58.34万 - 项目类别:
Coxiella manipulation of cholesterol in the intracellular niche
柯克斯体对细胞内生态位中胆固醇的操纵
- 批准号:
10270536 - 财政年份:2020
- 资助金额:
$ 58.34万 - 项目类别:
Coxiella manipulation of cholesterol in the intracellular niche
柯克斯体对细胞内生态位中胆固醇的操纵
- 批准号:
9919527 - 财政年份:2018
- 资助金额:
$ 58.34万 - 项目类别:
Coxiella manipulation of cholesterol in the intracellular niche
柯克斯体对细胞内生态位中胆固醇的操纵
- 批准号:
10386854 - 财政年份:2018
- 资助金额:
$ 58.34万 - 项目类别:
Reprogramming of host cell cholesterol homeostasis by Coxiella burnetii
伯氏柯克斯体对宿主细胞胆固醇稳态的重编程
- 批准号:
9195715 - 财政年份:2015
- 资助金额:
$ 58.34万 - 项目类别:
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