Systemic infections with non-typhoidal Salmonella
非伤寒沙门氏菌全身感染
基本信息
- 批准号:9238432
- 负责人:
- 金额:$ 23.55万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-12-12 至 2018-11-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAfrica South of the SaharaAfricanAgeAnimal ModelAnti-Bacterial AgentsAntibiotic ResistanceAntibiotic TherapyAntibioticsBacteremiaBacteriaBiologyBlood CirculationBone MarrowCessation of lifeChemotherapy-Oncologic ProcedureChildChildhoodDefectDevelopmentDiarrheaDiseaseEmergency SituationEpidemicEpidemiologyExploratory/Developmental GrantFatal OutcomeFocal InfectionGastroenteritisGenerationsGranulopoiesisHIVImmuneImmune responseImmunityImmunocompetentIndividualInfectionInterventionIntestinesKnowledgeLifeMalariaMalnutritionMeningitisMicronutrientsMulti-Drug ResistanceMusMuscle CrampNutrientOutcomePathogenesisPopulationPredispositionResearchRiskRisk FactorsRoleSalmonellaSalmonella entericaSalmonella infectionsSalmonella typhimuriumSepsisSerotypingSiteSystemic infectionTestingTretinoinTyphoid FeverVitamin AVitamin A DeficiencyVomitingWorkbaseexpectationimproved outcomeinnovationinsightkillingsmicronutrient deficiencymortalitymouse modelneutrophilnovelpreventresponse
项目摘要
ABSTRACT:
In healthy individuals, non-typhoidal Salmonella enterica serotypes (NTS) are associated with gastroenteritis, a
localized infection with low mortality manifesting as diarrhea, vomiting and intestinal cramping. However,
certain populations have long been known to be at increased risk of developing life-threatening systemic
infections, including the very young, those infected with HIV, and individuals undergoing cancer chemotherapy.
In these individuals, NTS infections are associated with bacteremia, which can progress to meningitis and
sepsis, often with a fatal outcome. In sub-Saharan Africa, there is currently an epidemic of disseminated NTS
infections, for which epidemiological associations suggest that the principal underlying factors in children are
young age, malaria and malnutrition. The basis for the effect of malnutrition on the outcome of Salmonella
infection is poorly understood, and it is unknown which specific nutrient deficiencies are responsible. One of
the most widespread micronutrient deficiencies in sub-Saharan African children is vitamin A deficiency.
However, it is unknown whether vitamin A deficiency renders individuals susceptible to disseminated NTS
infection, and if so, what the underlying mechanisms are. Given the high burden of Vitamin A deficiency in sub-
Saharan Africa, this gap in knowledge is important to address, as it could provide an intervention to reduce
development of disseminated NTS infection in young children. Our experimental evidence suggests that this
micronutrient, via its active metabolite, retinoic acid, is essential for preventing replication of NTS at systemic
sites. Further, we have shown that vitamin A-deficient mice are unable to generate mature neutrophils during
NTS infection. Based on these preliminary results, the overall objectives of this application are to define
Vitamin A-dependent immune mechanisms that control development of disseminated NTS infection, and to
explore feasibility of vitamin A administration as a adjunct to antibiotic treatment of multidrug resistant NTS
infection. The proposed work is highly innovative since specific mechanisms by which malnutrition affects
susceptibility to invasive NTS disease are not known. The fact that conditions predisposing to disseminated
NTS infections are understudied, even though they represent a major cause of mortality in sub-Saharan Africa,
makes the proposed work highly significant. We expect that the proposed research will provide important new
insights into specific immune mechanisms that are important for controlling invasive NTS disease, that may
extend to systemic infections with other bacteria as well. Therefore, the outcome of our proposed research is
likely to provide novel paradigms of how underlying conditions in the host affect the outcome of an infection.
文摘:
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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Renee M Tsolis其他文献
Renee M Tsolis的其他文献
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{{ truncateString('Renee M Tsolis', 18)}}的其他基金
2023 Salmonella Biology and Pathogenesis Gordon Research Conference and Seminar
2023年沙门氏菌生物学与发病机制戈登研究会议暨研讨会
- 批准号:
10683617 - 财政年份:2023
- 资助金额:
$ 23.55万 - 项目类别:
Neutrophil-intrinsic role of SLC11A1/NRAMP1 in control of bacterial infection
SLC11A1/NRAMP1 在控制细菌感染中的中性粒细胞内在作用
- 批准号:
10468025 - 财政年份:2019
- 资助金额:
$ 23.55万 - 项目类别:
Neutrophil-intrinsic role of SLC11A1/NRAMP1 in control of bacterial infection
SLC11A1/NRAMP1 在控制细菌感染中的中性粒细胞内在作用
- 批准号:
10224776 - 财政年份:2019
- 资助金额:
$ 23.55万 - 项目类别:
Neutrophil-intrinsic role of SLC11A1/NRAMP1 in control of bacterial infection
SLC11A1/NRAMP1 在控制细菌感染中的中性粒细胞内在作用
- 批准号:
10022095 - 财政年份:2019
- 资助金额:
$ 23.55万 - 项目类别:
2019 Microbial Adhesion and Signal Transduction GRC/GRS
2019微生物粘附与信号转导GRC/GRS
- 批准号:
9752745 - 财政年份:2019
- 资助金额:
$ 23.55万 - 项目类别:
Neutrophil-intrinsic role of SLC11A1/NRAMP1 in control of bacterial infection
SLC11A1/NRAMP1 在控制细菌感染中的中性粒细胞内在作用
- 批准号:
10683118 - 财政年份:2019
- 资助金额:
$ 23.55万 - 项目类别:
Neutrophil-intrinsic role of SLC11A1/NRAMP1 in control of bacterial infection
SLC11A1/NRAMP1 在控制细菌感染中的中性粒细胞内在作用
- 批准号:
10772361 - 财政年份:2019
- 资助金额:
$ 23.55万 - 项目类别:
Neutrophil-intrinsic role of SLC11A1/NRAMP1 in control of bacterial infection
SLC11A1/NRAMP1 在控制细菌感染中的中性粒细胞内在作用
- 批准号:
10755395 - 财政年份:2019
- 资助金额:
$ 23.55万 - 项目类别:
Detection of bacterial Type IV secretion by the unfolded protein response
通过未折叠蛋白反应检测细菌 IV 型分泌物
- 批准号:
8718850 - 财政年份:2014
- 资助金额:
$ 23.55万 - 项目类别:
Detection of bacterial Type IV secretion by the unfolded protein response
通过未折叠蛋白反应检测细菌 IV 型分泌物
- 批准号:
8874102 - 财政年份:2014
- 资助金额:
$ 23.55万 - 项目类别:
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