Central metabolism of Salmonella in the inflamed gut
发炎肠道中沙门氏菌的中枢代谢
基本信息
- 批准号:10411509
- 负责人:
- 金额:$ 4.94万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-02-24 至 2022-06-30
- 项目状态:已结题
- 来源:
- 关键词:AcidsAcuteAddressAnaerobic BacteriaAnimal Disease ModelsAnimal ModelBacterial ModelBiochemicalCarbonCell physiologyCitric Acid CycleColitisDental CalculusDevelopmentDiarrheaDiseaseEnergy MetabolismEnvironmentEpithelialEquilibriumFumaratesGastroenteritisGenesGeneticGoalsGrowthGut MucosaImmune responseImmunocompetentIn VitroIndividualInfectionInflammationInflammatoryInflammatory ResponseInterventionIntestinesIsomerismLarge IntestineLeadMedical Care CostsMetabolicMetabolismMethodsMicrobeModelingMolecularMucous MembraneNatureNitrogenNutritionalOperonOrganismOxidantsOxidesOxygenPathogenesisPathway interactionsPhasePopulationProductivityRegulationResearchRespirationSalmonellaSalmonella entericaSalmonella typhimuriumSerotypingSymptomsTartratesTestingTimeToxinUnited StatesVariantVirulenceVirulence FactorsWorkbacterial metabolismbasecommensal bacteriacostdiarrheal diseaseenteric pathogengut colonizationgut inflammationgut microbiotain vivoinnovationmetabolic abnormality assessmentmicrobialmicrobiotamurine colitisneutrophilnon-typhoidal Salmonellanoveloxidationpathogenpathogenic bacteriapathogenic microberational designsugar
项目摘要
PROJECT SUMMARY
Infection with the bacterial pathogen Salmonella enterica serovar Typhimurium (S. Tm) is a common cause of
inflammatory diarrhea. Intriguingly, intestinal inflammation drives an expansion of the S. Tm population in the
gut lumen. The molecular mechanisms that support S. Tm colonization of the intestinal tract remain
incompletely understood. Our central hypothesis is that the inflamed gut constitutes a peculiar nutritional
environment that enables S. Tm to outgrow obligate anaerobic commensal bacteria. We have recently
demonstrated that during the acute phase of the infection, neutrophil-derived electron acceptors facilitate an
oxidative central metabolism in S. Tm. In this application, we hypothesize that S. Tm relies on a branched TCA
cycle for initial gut colonization. In particular, tartaric acid, produced through oxidation of microbiota-liberated
sugars, supports fumarate reduction in the branched TCA cycle. We will test key aspects of our hypothesis by
pursuing the following specific aims: 1.) determine how utilization of D- and L-tartrate contributes to growth of
S. Tm in the lumen of the mammalian large intestine, 2.) determine the origin of tartrate during S. Tm infection,
and 3.) investigate the regulation of tartrate utilization genes in vitro and in vivo. This work will advance our
understanding of how intestinal pathogens, such as S. Tm, adapt their carbon and energy metabolism to
colonize the mammalian intestinal tract. We envision that a better understanding of the mechanisms by which
S. Tm outgrows competing microbes during inflammation will aid the development of new and innovative
approaches for treatment.
项目总结
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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Sebastian E Winter其他文献
Sebastian E Winter的其他文献
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{{ truncateString('Sebastian E Winter', 18)}}的其他基金
Metabolic Interactions between Salmonella and E. coli Nissle 1917
沙门氏菌和大肠杆菌 Nissle 之间的代谢相互作用 1917
- 批准号:
10663378 - 财政年份:2022
- 资助金额:
$ 4.94万 - 项目类别:
Metabolic Interactions between Salmonella and E. coli Nissle 1917
沙门氏菌和大肠杆菌 Nissle 之间的代谢相互作用 1917
- 批准号:
10509297 - 财政年份:2022
- 资助金额:
$ 4.94万 - 项目类别:
Central metabolism of Salmonella in the inflamed gut
发炎肠道中沙门氏菌的中枢代谢
- 批准号:
10677940 - 财政年份:2022
- 资助金额:
$ 4.94万 - 项目类别:
Central metabolism of Salmonella in the inflamed gut
发炎肠道中沙门氏菌的中枢代谢
- 批准号:
10535477 - 财政年份:2015
- 资助金额:
$ 4.94万 - 项目类别:
Central metabolism of Salmonella in the inflamed gut
发炎肠道中沙门氏菌的中枢代谢
- 批准号:
10721400 - 财政年份:2015
- 资助金额:
$ 4.94万 - 项目类别:
Central metabolism of Salmonella in the inflamed gut
发炎肠道中沙门氏菌的中枢代谢
- 批准号:
9058993 - 财政年份:2015
- 资助金额:
$ 4.94万 - 项目类别:
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