Determining the contribution of zinc deficiency to perinatal Group B Streptococcus infections
确定锌缺乏对围产期 B 族链球菌感染的影响
基本信息
- 批准号:9381886
- 负责人:
- 金额:$ 54.44万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-01 至 2022-05-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAmniotic FluidAnti-Bacterial AgentsAreaBacteriaBacterial InfectionsBehaviorChildClinicalClinical ResearchCost of IllnessDataDietDietary ZincDiseaseDisease OutcomeDisease ProgressionEnvironmentEventFetusGenetic PolymorphismGravidGravidityHomeostasisHost DefenseHumanImmune responseImmune systemImmunityInfectionIntoxicationInvadedKnowledgeLeadMaternal and Child HealthMembraneMicrobial BiofilmsMothersMucous MembraneMusNutritionalOutcomePathogenesisPerinatalPerinatal InfectionPopulationPregnancyPregnancy OutcomePregnant WomenPremature BirthPremature LaborPreventionPrevention approachProtein FamilyProteinsResistanceRiskRoleS100A12 geneS100A8 geneSerumSiteStreptococcal InfectionsStreptococcus Group BStructureSurfaceTestingTimeTissuesTranslational ResearchUterusVaginaVirulenceWorkZincZinc deficiencyZinc supplementationantimicrobialchelationcost effectivecytokinedisorder riskearly onsetfetal infectiongenome sequencingimprovedin vivointerestintraamniotic infectionlow and middle-income countriesmacrophagemicrobiomemicronutrient deficiencymouse modelneonatal sepsisneutrophilnovelnovel markernovel strategiesoffspringpathogenpregnantprematurepreventprotein expressionresponsevaginal microbiomewhole genome
项目摘要
Project Summary
Zinc deficiency is a global problem associated with preterm birth. Zinc supplementation has also been shown to
prevent preterm birth, but heterogeneous results of clinical studies suggest that certain, as yet undefined,
populations are likely to benefit from zinc more than others. Given the importance of infections as causes of
preterm birth, especially in regions affected by micronutrient deficiency, it is possible that low zinc levels
contribute to the risk for perinatal infections. However, little is known about this possible relationship. Group B
Streptococcus agalactiae (GBS) is a major cause of intrauterine infections during pregnancy, where it can invade
amniotic fluid and infect the developing fetus. The risk for perinatal GBS infections is highest in regions where
micronutrient deficiency is common. To cause intrauterine infection, GBS must first colonize the vagina, where
the low pH stimulates biofilm formation. The vaginal mucosa resists colonization by non-commensal bacteria
through a repertoire of antimicrobial molecules including S100A-family proteins (S100A8/A9 and S100A12) that
participate in nutritional immunity via zinc chelation. Neutrophils also secrete these proteins at sites of bacterial
infection. We have new and exciting data to suggest that zinc deficiency provokes major changes in the behavior
of GBS, with strong effects on the formation of biofilms, structures that aid in bacterial persistence in the
environment, which we speculate are important for vaginal colonization. Furthermore, we have also discovered
that GBS encoded a zinc efflux determinant, CadD, which promotes GBS resistance to zinc intoxication, survival
and persistence within macrophages, and ascending infection in a pregnant host. Given this, we hypothesize
that zinc deficiency, specifically in the context of pregnancy, leads to an increased risk for vaginal GBS
colonization and invasive infection. We will test this by determining the contribution of zinc homeostasis to
bacterial-host interactions, investigating the influence of zinc on immunological responses in human gestational
membranes and disease progression in a mouse model of invasive GBS infection, and evaluate the impact of
zinc homeostasis on GBS colonization in pregnant women. This work will identify novel biomarkers for increased
disease risk and cost-effective dietary or chemotherapeutic strategies that could improve pregnancy outcomes.
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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David M Aronoff其他文献
Infections caused by emClostridium perfringens/em and emPaeniclostridium sordellii/em after unsafe abortion
不安全流产后由产气荚膜梭菌和索氏梭菌引起的感染
- DOI:
10.1016/s1473-3099(22)00590-4 - 发表时间:
2023-02-01 - 期刊:
- 影响因子:31.000
- 作者:
David M Aronoff;Jeanne M Marrazzo - 通讯作者:
Jeanne M Marrazzo
David M Aronoff的其他文献
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{{ truncateString('David M Aronoff', 18)}}的其他基金
Bacterial CRISPR interference to define macrophage responses to group B Streptococcus proteins
细菌 CRISPR 干扰定义巨噬细胞对 B 族链球菌蛋白的反应
- 批准号:
10724607 - 财政年份:2023
- 资助金额:
$ 54.44万 - 项目类别:
Determining the contribution of zinc deficiency to perinatal Group B Streptococcus infections
确定锌缺乏对围产期 B 族链球菌感染的影响
- 批准号:
10163224 - 财政年份:2017
- 资助金额:
$ 54.44万 - 项目类别:
The Role of macrophages in chorioamnionitis and group B streptococcal infections
巨噬细胞在绒毛膜羊膜炎和 B 族链球菌感染中的作用
- 批准号:
10576123 - 财政年份:2017
- 资助金额:
$ 54.44万 - 项目类别:
The Role of macrophages in chorioamnionitis and group B streptococcal infections
巨噬细胞在绒毛膜羊膜炎和 B 族链球菌感染中的作用
- 批准号:
9978691 - 财政年份:2017
- 资助金额:
$ 54.44万 - 项目类别:
The Role of macrophages in chorioamnionitis and group B streptococcal infections
巨噬细胞在绒毛膜羊膜炎和 B 族链球菌感染中的作用
- 批准号:
10211123 - 财政年份:2017
- 资助金额:
$ 54.44万 - 项目类别:
The Role of macrophages in chorioamnionitis and group B streptococcal infections
巨噬细胞在绒毛膜羊膜炎和 B 族链球菌感染中的作用
- 批准号:
9403144 - 财政年份:2017
- 资助金额:
$ 54.44万 - 项目类别:
Prostaglandins as protective mediators in Clostridium difficile infection
前列腺素作为艰难梭菌感染的保护介质
- 批准号:
9316517 - 财政年份:2016
- 资助金额:
$ 54.44万 - 项目类别:
Repurposing misoprostol for Clostridium difficile colitis as identified by PheWAS
PheWAS 确定米索前列醇重新用于治疗艰难梭菌结肠炎
- 批准号:
9336367 - 财政年份:2016
- 资助金额:
$ 54.44万 - 项目类别:
Mechanisms of group B streptococcal interactions with extraplacental membranes
B 族链球菌与胎盘外膜相互作用的机制
- 批准号:
8507835 - 财政年份:2012
- 资助金额:
$ 54.44万 - 项目类别:
Epidemiology and Genomics of Clostridium difficile
艰难梭菌的流行病学和基因组学
- 批准号:
8026742 - 财政年份:2010
- 资助金额:
$ 54.44万 - 项目类别:
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