Phage depolymerases as antibiotics
Phage depolymerases as antibiotics
批准号:
9021386
负责人:
JAMES J BULL
金额:
$19.3万
依托单位国家:
美国
项目类别:
财政年份:
2015
资助国家:
美国
项目状态:
已结题
起止时间:
2015-12-01 至 2017-11-30
关键词:
AcinetobacterAntibioticsAntigensBackBacteriaBacterial CapsulesBacterial InfectionsBacteriophagesBiologicalCalibrationCell WallClinicalCloningCytolysisDevelopmentDirected Molecular EvolutionDisciplineEndotoxinsEnzymesEscherichia coliFoodFoundationsGenomicsGillsGoalsImmuneImmune systemInfectionKlebsiella pneumonia bacteriumMeasuresMethodsMusNatural ProductsNatureOrganismPathogenesisPharmaceutical PreparationsPhasePlasmidsPolysaccharidesPopulationPrincipal InvestigatorProteinsProtocols documentationResearchSourceSymptomsSystemTestingTherapeuticTherapeutic AgentsThickVariantVirusWorkantimicrobialantimicrobial drugbacterial resistancebasecapsulechemical propertyenzyme activityextracellularimprovedin vivointerestkillingslysinpathogenpathogenic bacteriaprogramspublic health relevancestandard caresuccess
中文摘要
英文摘要
DESCRIPTION (provided by applicant): This project develops a new class of antimicrobial drug against capsulated bacteria. Capsules are thick layers of extracellular polysaccharides that hinder access of most antimicrobial agents to the underlying organisms. The therapeutic agents are protein enzymes - depolymerases - that degrade the bacterial capsule and expose the bacterium to attack by the immune system. These new antimicrobial agents should have moderately broad host ranges and work on bacteria resistant to classical drugs. They have the further advantage that they do not kill bacteria per se, merely enabling the immune system to do the killing, and they thus do not release endotoxins that would exacerbate symptoms. The biological sources of these enzymes used in this work are bacteriophages, viruses that kill bacteria, which are easily isolated from the wild. Instead of using intact bacteriophages, we propose to use just the enzymes, which are encoded as parts of the bacteriophage tailspike. Sporadic studies dating back 84 years suggest that the enzymes alone can effect a cure for bacterial infections. The work here will establish the generality of earlier work, developing and implementing a protocol for the isolation, identification, and calibration of depolymerase activity
against arbitrary capsule types. The ultimate test provided here will be testing depolymerase efficacy in actual infections. A second direction of the work is to develop a protocol for evolving
higher and broader activity of depolymerases, improving on native enzymes obtained from the wild. The work here focuses on Klebsiella pneumoniae and E. coli, with extension to Acinetobacter baumanii in the later phases.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
2011 Microbial Population Biology Gordon Research Conference
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批准号:8123934
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项目类别:
-
资助金额:$0.8万
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财政年份:2011
-
负责人:JAMES J BULL
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依托单位:
Persistent viral attenuation by transcriptional and translational de-optimization
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批准号:9107913
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项目类别:
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资助金额:$31.18万
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财政年份:2009
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负责人:JAMES J BULL
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依托单位:
Persistent viral attenuation by transcriptional and translational de-optimization
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批准号:8963812
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项目类别:
-
资助金额:$31.0万
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财政年份:2009
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负责人:JAMES J BULL
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依托单位:
EXPERIMENTAL MODELS OF VIRAL ADAPTATION
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批准号:6138662
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项目类别:
-
资助金额:$23.12万
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财政年份:1998
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负责人:JAMES J BULL
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依托单位:
Experimental Models of Viral Genome Evolution
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批准号:6622157
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项目类别:
-
资助金额:$20.48万
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财政年份:1998
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负责人:JAMES J BULL
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依托单位:
EXPERIMENTAL MODELS OF VIRAL ADAPTATION
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批准号:6343022
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项目类别:
-
资助金额:$23.79万
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财政年份:1998
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负责人:JAMES J BULL
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依托单位:
Experimental models of viral genome evolution
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批准号:7105709
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项目类别:
-
资助金额:$19.07万
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财政年份:1998
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负责人:JAMES J BULL
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依托单位:
Experimental viral evolution at high mutation rate
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批准号:7983076
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项目类别:
-
资助金额:$20.72万
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财政年份:1998
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负责人:JAMES J BULL
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依托单位:
Experimental viral evolution at high mutation rate
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批准号:8324222
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项目类别:
-
资助金额:$20.58万
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财政年份:1998
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负责人:JAMES J BULL
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依托单位:
EXPERIMENTAL MODELS OF VIRAL ADAPTATION
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批准号:2650507
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项目类别:
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资助金额:$24.1万
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财政年份:1998
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负责人:JAMES J BULL
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依托单位:
Experimental Models of Viral Genome Evolution
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批准号:6440184
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项目类别:
-
资助金额:$20.48万
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财政年份:1998
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负责人:JAMES J BULL
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依托单位:
Experimental models of viral genome evolution
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批准号:7276002
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项目类别:
-
资助金额:$20.61万
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财政年份:1998
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负责人:JAMES J BULL
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依托单位:
Experimental Models of Viral Genome Evolution
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批准号:6710108
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项目类别:
-
资助金额:$20.48万
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财政年份:1998
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负责人:JAMES J BULL
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依托单位:
Experimental Models of Viral Genome Evolution
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批准号:6931873
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项目类别:
-
资助金额:$20.48万
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财政年份:1998
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负责人:JAMES J BULL
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依托单位:
EXPERIMENTAL MODELS OF VIRAL ADAPTATION
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批准号:2857369
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项目类别:
-
资助金额:$22.46万
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财政年份:1998
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负责人:JAMES J BULL
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依托单位:
Experimental viral evolution at high mutation rate
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批准号:8133330
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项目类别:
-
资助金额:$20.58万
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财政年份:1998
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负责人:JAMES J BULL
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依托单位:
Experimental viral evolution at high mutation rate
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批准号:8534141
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项目类别:
-
资助金额:$19.93万
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财政年份:1998
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负责人:JAMES J BULL
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依托单位:
Experimental models of viral genome evolution
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批准号:7490579
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项目类别:
-
资助金额:$20.01万
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财政年份:1998
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负责人:JAMES J BULL
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依托单位:
Experimental models of viral genome evolution
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批准号:7674690
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项目类别:
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资助金额:$18.51万
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财政年份:1998
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负责人:JAMES J BULL
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依托单位:
海外基金