Antimicrobial activity of Escherichia coli Nissle 1917 microcin M
大肠杆菌 Nissle 1917 microcin M 的抗菌活性
基本信息
- 批准号:10212238
- 负责人:
- 金额:$ 19.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-07-07 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAnaerobic BacteriaAnti-Bacterial AgentsAntibioticsBacteriaCatecholsCellsChelating AgentsDevelopmentDiarrheaEconomic BurdenElementsEnterobacteriaceaeEnterobactinEnvironmentEquus caballusEscherichia coliFamilyFocal InfectionFutureGastrointestinal tract structureGram-Negative BacteriaGrowthHealthHumanImmune responseIn VitroInfectionInterventionIronLeadLibrariesLightLinkMediatingMembraneMetalsMicrobeMorbidity - disease rateMulti-Drug ResistanceNutrientOrganismPalliative CarePatientsPeptidesPrevalenceProbioticsProcessPublic HealthRibosomesRunningSalmonellaSalmonella entericaSiderophoresTestingTherapeuticUnited StatesWorkantimicrobialantimicrobial peptidecellular targetingenteric pathogengut microbiomegut microbiotain vivoinflammatory disease of the intestinemicrobiotamicrocinmortalitymutantnon-typhoidal Salmonellanovel therapeutic interventionpathobiontpathogenpathogenic bacteriascreeningsiderophore receptorssmall moleculesuccesstargeted deliverytransmission processuptake
项目摘要
SUMMARY
Enterobacteriaceae are a family of Gram-negative bacteria that contains both commensals and pathogens
relevant to human health. Among the most prominent pathogens of this family is non-typhoidal Salmonella
enterica, a leading cause of infectious diarrhea worldwide. Key to this pathogen's success is its ability to elicit
intestinal inflammation, a host response that creates a hostile gut environment where many commensals are
depleted, but where Salmonella thrives, significantly increasing in abundance. During infection, pathogens must
acquire essential metal nutrients such as iron, an element that is highly limited by the host. In preliminary studies,
we found that the probiotic bacterium Escherichia coli Nissle 1917 can compete with Salmonella and other enteric
pathogens in the inflamed gut by producing antibacterial peptides termed microcins. In particular, we found that
Salmonella is susceptible to microcin M in iron-limited conditions and in the inflamed gut. The primary objective
of this application is to elucidate the antimicrobial activity of E. coli Nissle's microcin M (MccM) in vitro and in
vivo. Our central hypothesis is that conjugation to catecholate siderophores enables MccM to more selectively
target bacteria that express specific siderophore receptors in the Fe-limited host environment, without affecting
the gut microbiota at large. We plan to test our hypothesis and fulfill the objectives of this application by pursuing
the following two Specific Aims. In Aim 1, we will determine whether siderophore conjugation and siderophore
uptake machinery influences the antimicrobial activity of MccM, and we will identify putative cellular targets of
MccM activity by screening mutant libraries. Investigate the mechanisms underlying the selectivity of MccM
antimicrobial activity. In Aim 2, we will ascertain the antimicrobial activity of MccM against non-typhoidal
Salmonella in vivo, and we will determine whether administration of purified MccM perturbs the gut
microbiome.This work may lead to future development of microcins as therapeutics to limit colonization and
transmission of non-typhoidal Salmonella, and possibly other enteric pathogens and pathobionts, in an
environment that is otherwise favorable to their growth.
摘要
肠杆菌科是革兰氏阴性菌家族,既有共生菌又有病原菌。
与人类健康相关。该家族最主要的病原体是非伤寒沙门氏菌。
肠炎,是全球感染性腹泻的主要原因。这种病原体成功的关键是它能够诱导
肠炎,一种宿主反应,创造了一个敌对的肠道环境,其中许多共生体
沙门氏菌已经枯竭,但沙门氏菌在那里茁壮成长,数量显著增加。在感染期间,病原体必须
获取基本的金属营养,如铁,这是一种受宿主高度限制的元素。在初步研究中,
我们发现,益生菌大肠杆菌Nissle 1917可以与沙门氏菌等肠道细菌竞争
通过产生称为微球蛋白的抗菌肽,在发炎的肠道中产生病原体。特别是,我们发现,
沙门氏菌在铁限制的条件下和发炎的肠道中对微菌素M敏感。首要目标是
目的:阐明大肠杆菌尼氏微球菌素M(MCCM)的体外和体外抗菌活性。
活着。我们的中心假设是,与儿茶酚类铁载体的结合使MCCM能够更有选择性地
在铁限制的宿主环境中表达特定铁载体受体的靶标细菌,而不影响
肠道微生物区系普遍存在。我们计划测试我们的假设,并通过以下方式实现此应用程序的目标
以下两个具体目标。在目标1中,我们将确定铁载体结合和铁载体
摄取机制影响MCCM的抗菌活性,我们将确定其可能的细胞靶点
通过筛选突变体库来检测MCCM的活性。探讨MCCM选择性的机制
抗菌活性。在目标2中,我们将确定MCCM对非伤寒的抗菌活性。
沙门氏菌在体内,我们将确定给予纯化的MCCM是否会扰乱肠道
微生物组。这项工作可能会导致微囊素作为治疗药物的未来发展,以限制定植和
非伤寒沙门氏菌的传播,可能还有其他肠道病原体和致病菌
其他方面有利于它们成长的环境。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Salmonella respiration turns the tables on propionate.
- DOI:10.1016/j.tim.2022.01.011
- 发表时间:2022-03
- 期刊:
- 影响因子:15.9
- 作者:Walker GT;Raffatellu M
- 通讯作者:Raffatellu M
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
ELIZABETH M NOLAN其他文献
ELIZABETH M NOLAN的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('ELIZABETH M NOLAN', 18)}}的其他基金
Harnessing iron acquisition to hinder enterobacterial pathogenesis
利用铁的获取来阻碍肠细菌的发病机制
- 批准号:
10651432 - 财政年份:2023
- 资助金额:
$ 19.38万 - 项目类别:
Metallobiochemistry of innate immunity and bacterial physiology
先天免疫的金属生物化学和细菌生理学
- 批准号:
9436092 - 财政年份:2017
- 资助金额:
$ 19.38万 - 项目类别:
Bioinorganic Explorations of Host-Defense Proteins
宿主防御蛋白的生物无机探索
- 批准号:
9982335 - 财政年份:2017
- 资助金额:
$ 19.38万 - 项目类别:
Metallobiochemistry of innate immunity and bacterial physiology
先天免疫的金属生物化学和细菌生理学
- 批准号:
10305443 - 财政年份:2017
- 资助金额:
$ 19.38万 - 项目类别:
Bioinorganic Explorations of Host-Defense Proteins
宿主防御蛋白的生物无机探索
- 批准号:
9239551 - 财政年份:2017
- 资助金额:
$ 19.38万 - 项目类别:
Bioinorganic Explorations of Host-defense Proteins
宿主防御蛋白的生物无机探索
- 批准号:
10530840 - 财政年份:2017
- 资助金额:
$ 19.38万 - 项目类别:
Bioinorganic Explorations of Host-Defense Proteins
宿主防御蛋白的生物无机探索
- 批准号:
9752605 - 财政年份:2017
- 资助金额:
$ 19.38万 - 项目类别:
Bioinorganic Explorations of Host-defense Proteins
宿主防御蛋白的生物无机探索
- 批准号:
10662538 - 财政年份:2017
- 资助金额:
$ 19.38万 - 项目类别:
Metallobiochemistry of innate immunity and bacterial physiology
先天免疫的金属生物化学和细菌生理学
- 批准号:
10468860 - 财政年份:2017
- 资助金额:
$ 19.38万 - 项目类别:
Metallobiochemistry of innate immunity and bacterial physiology
先天免疫的金属生物化学和细菌生理学
- 批准号:
10686285 - 财政年份:2017
- 资助金额:
$ 19.38万 - 项目类别:
相似海外基金
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 19.38万 - 项目类别:
Standard Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 19.38万 - 项目类别:
Standard Grant
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 19.38万 - 项目类别:
Training Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 19.38万 - 项目类别:
Fellowship
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 19.38万 - 项目类别:
Research Grant
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 19.38万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 19.38万 - 项目类别:
Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
- 批准号:
2301846 - 财政年份:2023
- 资助金额:
$ 19.38万 - 项目类别:
Standard Grant
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 19.38万 - 项目类别:
Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
- 批准号:
23K16076 - 财政年份:2023
- 资助金额:
$ 19.38万 - 项目类别:
Grant-in-Aid for Early-Career Scientists