Microbial ecology of the inflamed intestine
Microbial ecology of the inflamed intestine
批准号:
9789832
负责人:
Brian M Ahmer
金额:
$70.6万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-09-24 至 2023-08-31
关键词:
AdultAffectAgricultureAnimalsAntibiotic ResistanceAntibioticsAsparagineBacteriaBacterial InfectionsBiologicalBiological AssayCBA/J MouseCenters for Disease Control and Prevention (U.S.)ChemicalsChemistryChildClostridiumCoupledCrohn&aposs diseaseDataDietDiseaseDisease modelEcologyEcosystemElderlyEnterobacteriaceaeEnvironmentEnzymesEthanolaminesFloodsFructoseFutureGalactoseGenomeGenomicsGlucoseGoalsGrowthHumanImmunocompromised HostIn VitroIndividualInfectionInflammationInflammatoryInflammatory Bowel DiseasesInterventionIntestinesKnowledgeLeadMediatingMetabolicMicrobeModelingMorbidity - disease rateNutrientOxidantsPathway interactionsPhysiologyPredispositionProbioticsProcessPropylene GlycolsReportingResearchResistance developmentResolutionSalmonellaSalmonella entericaSalmonella infectionsSamplingSerotypingSeveritiesSodium Dextran SulfateSourceStructureSystemTechnologyTestingTherapeuticTimeTranslatingUlcerative ColitisUnited StatesVaccinesViralVirus Diseasesbasecarbapenem-resistant Enterobacteriaceaecell injurycommensal microbesfoodborne illnessfoodborne infectionfoodborne pathogengastrointestinal infectiongut microbiomegut microbiotaimprovedin vivometabolomemetabolomicsmicrobialmicrobial communitymicrobiotamicroorganism interactionmortalitymouse modelmultiple omicsnon-typhoidal Salmonellanormal microbiotanovel strategiesnovel therapeutic interventionoxidationpathogenprebioticsprophylactictherapeutic target
中文摘要
项目摘要
沙门氏菌病是影响人类和农业的最重要的食源性疾病之一。沙门
肠毒素引起宿主肠道的炎症,这破坏了正常的微生物群。沙门
然后靠微生物群不消耗的营养物质繁衍。沙门氏菌的营养来源包括1,2-
乙醇胺,其来源于受损细胞;
葡糖二酸和半乳糖二酸,其衍生自Nos 2介导的葡萄糖和半乳糖的氧化;和
果糖-天冬酰胺(F-Asn),来源于饮食。F-Asn利用系统提供了
一个有趣的治疗靶点,因为FraB酶的抑制使细菌中毒,
中间体我们的主要目标是使用系统水平的方法来确定主要的营养源
随着时间的推移,沙门氏菌在发炎的肠道中利用这些细菌,并确定竞争这些细菌的微生物。
营养素我们假设,这些营养获取系统中的一些将提供治疗靶点,
沙门氏菌和潜在的其他肠杆菌科,包括碳青霉烯类耐药肠杆菌科
(CRE)疾病预防控制中心的报告“美国的抗生素耐药性威胁”将其列为“紧急”威胁。
国家”。在其他情况下,我们假设竞争的微生物可以被用作益生菌或益生菌。
所利用的营养物可用作益生元。我们建议实现我们的目标,并测试我们的假设
主要有两个目的:1)确定沙门氏菌介导的化学和生物学指标
随着时间的推移炎症; 2)表征沙门氏菌及其竞争对手之间的代谢交换,
直觉这些目标的实现将大大扩展我们对微生物生态学的理解。
沙门氏菌病,并可能广泛相关的其他病原体或相关的炎症性疾病。
英文摘要
Project Summary
Salmonellosis is one of the most significant food-borne diseases affecting humans and agriculture. Salmonella
enterica induces inflammation of the host intestinal tract, which disrupts the normal microbiota. Salmonella
then thrives on the nutrients that are not consumed by the microbiota. Salmonella nutrient sources include 1,2-
propanediol, which is a product of the microbiota; ethanolamine, which is derived from damaged cells;
glucarate and galactarate which are derived from Nos2-mediated oxidation of glucose and galactose; and
fructose-asparagine (F-Asn) which is derived from the diet. The F-Asn utilization system provides an
interesting therapeutic target as inhibition of the FraB enzyme intoxicates the bacterium with a metabolic
intermediate. Our primary objectives are to use a systems-level approach to identify the major nutrient sources
utilized by Salmonella over time in the inflamed gut and to identify the microbes that compete for those
nutrients. We hypothesize that some of these nutrient acquisition systems will provide therapeutic targets for
Salmonella and potentially other Enterobacteriaceae, including the carbapenem-resistant Enterobacteriaceae
(CRE) that are classified as an “urgent” threat by the CDC report, “Antibiotic resistance threats in the United
States”. In other cases, we hypothesize that the competing microbes could be utilized as probiotics or the
nutrients utilized could be utilized as prebiotics. We propose to fulfill our objectives and test our hypotheses
with the following two aims: 1) Identify the chemical and biological indicators of Salmonella-mediated
inflammation over time; 2) characterize metabolic exchanges between Salmonella and its competitors in the
gut. The fulfillment of these aims will greatly expand our understanding of the microbial ecology of
salmonellosis and may be broadly relevant to other pathogens or related inflammatory disorders.
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会议论文
Microbial ecology of the inflamed intestine
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批准号:10462602
-
项目类别:
-
资助金额:$70.6万
-
财政年份:2018
-
负责人:Brian M Ahmer
-
依托单位:
Salmonella-specific therapeutics
-
批准号:9764264
-
项目类别:
-
资助金额:$71.95万
-
财政年份:2018
-
负责人:Brian M Ahmer
-
依托单位:
Salmonella-specific therapeutics
-
批准号:10215469
-
项目类别:
-
资助金额:$63.53万
-
财政年份:2018
-
负责人:Brian M Ahmer
-
依托单位:
Microbial ecology of the inflamed intestine
-
批准号:10227082
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项目类别:
-
资助金额:$70.6万
-
财政年份:2018
-
负责人:Brian M Ahmer
-
依托单位:
Salmonella, colonization resistance, and fructose-asparagine
-
批准号:8966010
-
项目类别:
-
资助金额:$49.66万
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财政年份:2014
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负责人:Brian M Ahmer
-
依托单位:
Salmonella, colonization resistance, and fructose-asparagine
-
批准号:9184529
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项目类别:
-
资助金额:$49.66万
-
财政年份:2014
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负责人:Brian M Ahmer
-
依托单位:
Coordination of metabolism and virulence during infection
-
批准号:8214355
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项目类别:
-
资助金额:$38.69万
-
财政年份:2011
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负责人:Brian M Ahmer
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依托单位:
Coordination of metabolism and virulence during infection
-
批准号:8582536
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项目类别:
-
资助金额:$49.06万
-
财政年份:2011
-
负责人:Brian M Ahmer
-
依托单位:
Coordination of metabolism and virulence during infection
-
批准号:8374104
-
项目类别:
-
资助金额:$40.98万
-
财政年份:2011
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负责人:Brian M Ahmer
-
依托单位:
Salmonella polymicrobial interactions
-
批准号:8063534
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项目类别:
-
资助金额:$50.06万
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财政年份:2008
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负责人:Brian M Ahmer
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依托单位:
Salmonella polymicrobial interactions
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批准号:8264043
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项目类别:
-
资助金额:$8.05万
-
财政年份:2008
-
负责人:Brian M Ahmer
-
依托单位:
Salmonella polymicrobial interactions
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批准号:8259465
-
项目类别:
-
资助金额:$58.03万
-
财政年份:2008
-
负责人:Brian M Ahmer
-
依托单位:
Salmonella polymicrobial interactions
-
批准号:7527342
-
项目类别:
-
资助金额:$50.51万
-
财政年份:2008
-
负责人:Brian M Ahmer
-
依托单位:
Salmonella polymicrobial interactions
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批准号:7808091
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项目类别:
-
资助金额:$57.86万
-
财政年份:2008
-
负责人:Brian M Ahmer
-
依托单位:
Salmonella polymicrobial interactions
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批准号:7623026
-
项目类别:
-
资助金额:$59.73万
-
财政年份:2008
-
负责人:Brian M Ahmer
-
依托单位:
Detection of Mixed Microbial Communities by Salmonella
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批准号:6511599
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项目类别:
-
资助金额:$22.12万
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财政年份:2001
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负责人:Brian M Ahmer
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依托单位:
Detection of mixed microbial communities by Salmonella
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批准号:7252347
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项目类别:
-
资助金额:$30.0万
-
财政年份:2001
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负责人:Brian M Ahmer
-
依托单位:
Detection of Mixed Microbial Communities by Salmonella
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批准号:6362006
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项目类别:
-
资助金额:$19.85万
-
财政年份:2001
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负责人:Brian M Ahmer
-
依托单位:
Detection of Mixed Microbial Communities by Salmonella
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批准号:6632478
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项目类别:
-
资助金额:$22.13万
-
财政年份:2001
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负责人:Brian M Ahmer
-
依托单位:
Detection of Mixed Microbial Communities by Salmonella
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批准号:6742401
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项目类别:
-
资助金额:$22.13万
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财政年份:2001
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负责人:Brian M Ahmer
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依托单位:
海外基金