A bacterial biosensor for intracellular metal availability in the gut
用于肠道内细胞内金属可用性的细菌生物传感器
基本信息
- 批准号:10353307
- 负责人:
- 金额:$ 5.85万
- 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:2022-04-22 至 2022-12-16
- 项目状态:已结题
- 来源:
- 关键词:AddressAdoptedAffectAffinityAnatomyBackBacteriaBacterial InfectionsBinding ProteinsBiosensorCattleCell physiologyCell surfaceCellsCessation of lifeClinicalCommunicable DiseasesComplexCytosolDefense MechanismsDiseaseDivalent CationsEffectivenessEnteralEpithelialEpithelial CellsExtracellular SpaceFamilyFamily memberFluorescence MicroscopyGastroenteritisGene ExpressionGenesGenetic TranscriptionGoalsGrowthHomeostasisHomologous GeneHost DefenseHost Defense MechanismHumanImmuneImmunocompromised HostIndividualInfectionIngestionIntestinal MucosaIntestinesInvadedIonsIronIron Chelating AgentsKnowledgeLamina PropriaLifeLife StyleMammalian CellMammalsManganeseMapsMediatingMembraneMessenger RNAMetabolismMetalsMicrobeMicronutrientsModelingMusMutationMyelogenousMyeloid CellsNeutrophil InfiltrationNutrientNutritional ImmunityOrganismOutcomeParasitesParasitic infectionPathogenicityPhagocytesPlayPredispositionPreventionProtein FamilyProtein IsoformsProtozoaReporterRoleSLC11A2 geneSalmonellaSalmonella entericaSalmonella infectionsSalmonella typhimuriumSiderophoresTimeToxic effectTransition ElementsVacuoleVirulenceVirulence FactorsVirus DiseasesWarWorkZincantimicrobialapical membranearms raceburden of illnesscell typedefined contributiondeprivationdivalent metalefflux pumpenteric infectionenteritisexperienceexperimental studyextracellularfightingfoodbornefoodborne illnessfungusgastrointestinal epitheliumgut colonizationintestinal epitheliumiron deficiencyknock-downmacrophagemanmicrobialmicroorganismmouse modelnatural resistance-associated macrophage protein 1neutrophilnew therapeutic targetnon-typhoidal Salmonellaoutcome predictionpathogenpreventresponsespatiotemporaluptake
项目摘要
PROJECT SUMMARY
Of the foodborne bacterial, protozoal and viral diseases, non-typhoidal Salmonella enterica cause the largest
burden of illness and death worldwide. The most common human clinical isolates are Salmonella enterica
serovars Typhimurium (S. Typhimurium, STm) and Enteriditis (S. Enteriditis). Infection can cause either a self-
limiting gastroenteritis or a life-threatening, invasive disease in immunocompromised individuals. During enteric
infection, STm adopts both extracellular and intracellular lifestyles, colonizing the intestinal lumen as well
epithelial cells and phagocytes in the intestinal mucosa. Here we will study how host-mediated restriction of
transition metals, known as nutritional immunity, affects STm colonization of the gut. The NRAMP family of
proteins are “promiscuous” transporters of divalent cations that play a major role in metal ion homeostasis from
bacteria to man. In mammals, there are two NRAMP genes, SLC11A1 and SLC11A2 in humans and Slc11a1
and Slc11a2 in mice. Slc11a1 is restricted to the myeloid lineage whereas Slc11a2 is ubiquitously expressed.
Whilst the role of Slc11a1 in controlling intracellular bacterial and parasitic infections in macrophages and mice
is undisputed, whether Slc11a2 also contributes to antimicrobial functions is unknown. Our general hypothesis
is that intracellular metal ion availability differs in epithelial cells and phagocytes in the gut due to the distinct
cell-type expression of SLC11A1 and SLC11A2. First, we will use microbial biosensors of metal ion
concentrations to infect bovine ligated ileal loops, a highly relevant model of enteric salmonellosis in humans,
and map the spatiotemporal distribution of metal ion deprivation in the gut. Second, we will define whether
SLC11A2, the sole NRAMP family member expressed in intestinal epithelial cells, defends against invading
pathogens via metal nutrient limitation. Completion of this proposal will close a significant knowledge gap about
host-microbe competition for metal ions in the gut during enteric infection.
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)
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Leigh Knodler其他文献
Leigh Knodler的其他文献
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{{ truncateString('Leigh Knodler', 18)}}的其他基金
A bacterial biosensor for intracellular metal availability in the gut
用于肠道内细胞内金属可用性的细菌生物传感器
- 批准号:
10763683 - 财政年份:2022
- 资助金额:
$ 5.85万 - 项目类别:
A bacterial biosensor for intracellular metal availability in the gut
用于肠道内细胞内金属可用性的细菌生物传感器
- 批准号:
10764453 - 财政年份:2022
- 资助金额:
$ 5.85万 - 项目类别:
Epithelial intrinsic inflammasomes direct host defense against gut microbes
上皮内在炎症小体直接引导宿主防御肠道微生物
- 批准号:
10801424 - 财政年份:2018
- 资助金额:
$ 5.85万 - 项目类别:
Epithelial intrinsic inflammasomes direct host defense against gut microbes
上皮内在炎症小体直接引导宿主防御肠道微生物
- 批准号:
10202411 - 财政年份:2018
- 资助金额:
$ 5.85万 - 项目类别:
Epithelial intrinsic inflammasomes direct host defense against gut microbes
上皮内在炎症小体直接引导宿主防御肠道微生物
- 批准号:
10428520 - 财政年份:2018
- 资助金额:
$ 5.85万 - 项目类别:
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