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.
项目摘要
锌缺乏是一个全球性的问题与早产。补充锌也被证明
预防早产,但临床研究的异质性结果表明,某些尚未确定的,
人群可能比其他人群更能从锌中受益。鉴于感染是导致
早产,特别是在受微量营养素缺乏影响的地区,可能是锌水平低
会增加围产期感染的风险。然而,人们对这种可能的关系知之甚少。B组
无乳链球菌(GBS)是妊娠期间宫内感染的主要原因,它可以侵入
感染发育中的胎儿围产期GBS感染的风险在以下地区最高:
微量营养素缺乏症很常见。要引起宫内感染,GBS必须首先定植在阴道,
低pH刺激生物膜形成。阴道粘膜抵抗非阴道细菌的定植
通过包括S100 A家族蛋白(S100 A8/A9和S100 A12)的抗微生物分子库,
通过锌螯合作用参与营养免疫。嗜中性粒细胞也在细菌感染部位分泌这些蛋白质。
感染我们有新的令人兴奋的数据表明,锌缺乏引起的行为的重大变化,
的GBS,具有强烈的影响,形成生物膜,结构,有助于细菌的持久性,
环境,我们推测这对阴道定植很重要。此外,我们还发现,
GBS编码一个锌外排决定簇CadD,它促进GBS抵抗锌中毒,存活
在巨噬细胞内持续存在,以及在怀孕宿主中的上行感染。鉴于此,我们假设
锌缺乏,特别是在怀孕的情况下,导致阴道GBS的风险增加
定植和侵入性感染。我们将通过确定锌稳态对
细菌-宿主相互作用,研究锌对人类妊娠期免疫反应的影响,
膜和疾病进展的侵袭性GBS感染的小鼠模型,并评估的影响,
锌稳态对孕妇GBS定植的影响这项工作将确定新的生物标志物,
疾病风险和具有成本效益的饮食或化疗策略,可以改善怀孕结果。
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:
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:
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:
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:
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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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