Mechanisms of Nutrient Competition in the Intestine
肠道营养竞争机制
基本信息
- 批准号:9220348
- 负责人:
- 金额:$ 30.4万
- 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:2017-03-01 至 2021-01-31
- 项目状态:已结题
- 来源:
- 关键词:AllelesAnaerobic BacteriaAnimal ModelAnimalsBacteriaChildCommunitiesConsumptionDiarrheaDiseaseEcosystemEnteralEnterobacteriaceaeEnvironmentEscherichia coliEscherichia coli EHECEscherichia coli O157:H7FecesFundingGenesGenomeGenomicsGrowthHealthHumanIn VitroInfectionInfection preventionInfectious AgentIngestionIntestinesInvadedKineticsLaboratory cultureLarge IntestineLeadMaintenanceMeasurementMeasuresMicrobeModelingMucous body substanceMusNutrientNutritionalOperonPathogenesisPathogenicityPathway interactionsPhysiologyPopulationProcessPropertyRNAResearchResistanceResourcesSamplingSourceStreptomycinSymbiosisSystemTestingUnited States National Institutes of HealthWorld Health Organizationbasecommensal microbesdesignenteric pathogenexperimental studyfeedingfitnessgut microbiotain vivoinsightkillingsmetabolomicsmicrobiotamicroorganismmouse modelmutantpathogenpathogen genomepreventsuccesstranscriptome sequencingtranscriptomics
项目摘要
PROJECT SUMMARY/ABSTRACT
The World Health Organization classifies diarrhea as a significant worldwide health threat, killing thousands of
children daily. Ingestion of a small number of infectious organisms can lead to trillions of pathogens being shed
in the stool. Therefore, we postulate that enteric pathogens such as enterohemorrhagic E. coli possess potent
mechanisms for obtaining nutrients that provide the energy needed to replicate rapidly in the intestine. While
many of the nutrients that support intestinal colonization by model organisms are known, the mechanisms
underlying competition for those nutrients are poorly understood. With NIH funding and a research strategy
built on the streptomycin treated mouse model, we previously identified the nutrients that support colonization
by six genome-sequenced, genetically tractable, prototypical pathogenic and commensal E. coli strains. While
these bacteria essentially use the same growth substrates in laboratory culture, each uses a different subset of
the available nutrients in the intestine. Indeed, different E. coli strains can co-colonize with one another,
indicating that they occupy distinct niches. Two commensal E. coli strains were found to exert colonization
resistance against E. coli O157:H7. On the other hand, two other pathotypes were able to overcome
colonization resistance to co-colonize with the same commensals. According to basic ecological principles, the
niches occupied by competing bacteria are defined by nutrient availability. An important prediction of the
nutrient-niche hypothesis is that resistance or sensitivity to invasion depends on nutrient consumption by the
resident microbiota, but there is little supporting evidence. Importantly, we recently proved that colonization
resistance is imparted by the facultative anaerobes. The question is: how do pathogens overcome colonization
resistance to initiate infections? In the streptomycin treated mouse model of competitive colonization, the
facultative microbiota can be manipulated to consist of carefully chosen, well-characterized commensal E. coli
strain(s) that either exert colonization resistance, or not, against selected pathotypes. The proposed research
strategy tests the hypothesis that successful invasion by enteric pathogens depends on potent mechanisms to
compete for the nutrients needed to replicate in the intestine. In Aim 1 the competitive colonization model will
be used to measure the nutrients that are available to invading pathogens and genome-specific RNA
sequencing will determine the catabolic gene systems that are induced in the competing E. coli pathogens and
commensals in the intestine. Aim 2 will focus on the mechanisms of nutrient competition between E. coli
pathogens and commensals by direct measurement of nutrient consumpition in vivo. To identify allelic
differences in catabolic genes that confer fitness advantages, catabolic operons will be swapped between
strains and their competitive fitness will be assessed in animals. These experiments are designed to elucidate
the mechanisms of nutrient acquisition that are critical to establishing infection. A better understanding of how
enteric pathogens compete with the microbiota for nutrients is needed to prevent intestinal infections.
项目摘要/摘要
世界卫生组织将腹泻列为严重的全球健康威胁,导致数千人死亡
每天都有孩子。摄入少量的感染性生物可导致数万亿病原体被排出
在凳子上。因此,我们推测肠出血性大肠杆菌等肠道病原体具有较强的致病性。
获得营养的机制,以提供在肠道中快速复制所需的能量。而当
许多支持模式生物肠道定植的营养物质是已知的,其机制
人们对这些营养物质的潜在竞争知之甚少。美国国立卫生研究院的资助和一项研究战略
建立在链霉素处理的小鼠模型上,我们之前确定了支持定植的营养物质
由六个基因组测序的、遗传上易处理的、典型致病的和共生的大肠杆菌菌株。而当
这些细菌在实验室培养中基本上使用相同的生长底物,每种使用不同的子集
肠道中可利用的营养物质。事实上,不同的大肠杆菌菌株可以相互共存,
这表明它们占据了不同的生态位。发现两个共生的大肠杆菌菌株具有定植作用。
对O157:H7大肠杆菌的耐药性。另一方面,另外两种致病类型能够克服
殖民抵抗与共同殖民具有相同的共生性。根据生态学的基本原理,
竞争细菌占据的生态位取决于营养的可获得性。一项重要的预测
营养生态位假说认为,对入侵的抵抗力或敏感性取决于
居民微生物区系,但几乎没有支持证据。重要的是,我们最近证明了殖民
抵抗力是由兼性厌氧菌传递的。问题是:病原体如何克服殖民
对引发感染的抵抗力?在链霉素处理的竞争定植的小鼠模型中,
兼性微生物区系可以被操纵成由精心挑选的、特征良好的共生大肠杆菌组成
对选定的致病类型产生定殖抗性或不产生定植抗性的菌株(S)。拟议的研究
战略测试的假设是,肠道病原体的成功入侵取决于有效的机制
争夺在肠道中复制所需的营养。在目标1中,竞争性殖民模式将
被用来测量入侵病原体和基因组特定RNA可用的营养物质
测序将确定在竞争的大肠杆菌和
肠道内的连合处。目标2将侧重于大肠杆菌之间营养竞争的机制
通过直接测量体内营养消耗的病原体和共生体。鉴定等位基因
赋予健康优势的分解代谢基因的差异,分解代谢操纵子将在
菌株及其竞争适合度将在动物身上进行评估。这些实验旨在阐明
对确定感染至关重要的营养获取机制。更好地了解如何
肠道病原体与微生物群竞争预防肠道感染所需的营养。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
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 }}
TYRRELL CONWAY其他文献
TYRRELL CONWAY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('TYRRELL CONWAY', 18)}}的其他基金
Symbiosis of E. coli and the Intestinal Microbiota in a Mouse Model
小鼠模型中大肠杆菌与肠道微生物群的共生
- 批准号:
8401893 - 财政年份:2011
- 资助金额:
$ 30.4万 - 项目类别:
Symbiosis of E. coli and the Intestinal Microbiota in a Mouse Model
小鼠模型中大肠杆菌与肠道微生物群的共生
- 批准号:
8505684 - 财政年份:2011
- 资助金额:
$ 30.4万 - 项目类别:
Symbiosis of E. coli and the Intestinal Microbiota in a Mouse Model
小鼠模型中大肠杆菌与肠道微生物群的共生
- 批准号:
8600292 - 财政年份:2011
- 资助金额:
$ 30.4万 - 项目类别:
Symbiosis of E. coli and the Intestinal Microbiota in a Mouse Model
小鼠模型中大肠杆菌与肠道微生物群的共生
- 批准号:
8302475 - 财政年份:2011
- 资助金额:
$ 30.4万 - 项目类别:
Symbiosis of E. coli and the Intestinal Microbiota in a Mouse Model
小鼠模型中大肠杆菌与肠道微生物群的共生
- 批准号:
8015175 - 财政年份:2011
- 资助金额:
$ 30.4万 - 项目类别:
Symbiosis of E. coli and the Intestinal Microbiota in a Mouse Model
小鼠模型中大肠杆菌与肠道微生物群的共生
- 批准号:
8206549 - 财政年份:2011
- 资助金额:
$ 30.4万 - 项目类别:
BIOINFORMATICS/MICROARRAY SATELLITE CORE-OU NORMAN
生物信息学/微阵列卫星 Core-OU Norman
- 批准号:
7960010 - 财政年份:2009
- 资助金额:
$ 30.4万 - 项目类别:
BIOINFORMATICS/MICROARRAY SATELLITE CORE-OU NORMAN
生物信息学/微阵列卫星 Core-OU Norman
- 批准号:
7725088 - 财政年份:2008
- 资助金额:
$ 30.4万 - 项目类别:
BIOINFORMATICS/MICROARRAY SATELLITE CORE-OU NORMAN
生物信息学/微阵列卫星 Core-OU Norman
- 批准号:
7610268 - 财政年份:2007
- 资助金额:
$ 30.4万 - 项目类别:
相似海外基金
Identification and isolation of anaerobic bacteria that degrade bacterial cell wall
降解细菌细胞壁的厌氧菌的鉴定与分离
- 批准号:
22H02487 - 财政年份:2022
- 资助金额:
$ 30.4万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Enzymology of cofactor and amino acid metabolism in anaerobic bacteria
厌氧菌辅助因子和氨基酸代谢的酶学
- 批准号:
RGPIN-2022-03200 - 财政年份:2022
- 资助金额:
$ 30.4万 - 项目类别:
Discovery Grants Program - Individual
High-throughput isolation of anaerobic bacteria
厌氧菌的高通量分离
- 批准号:
572711-2022 - 财政年份:2022
- 资助金额:
$ 30.4万 - 项目类别:
University Undergraduate Student Research Awards
Elucidating the mechanisms of O2-sensitivity of anaerobic bacteria Bifidobacterium.
阐明厌氧菌双歧杆菌的 O2 敏感性机制。
- 批准号:
22K07058 - 财政年份:2022
- 资助金额:
$ 30.4万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Automatic and accurate identification of aerobic bacteria, anaerobic bacteria, yeasts, and fungi in clinical samples derived from animals and from feed for pets
自动、准确地鉴定来自动物和宠物饲料的临床样品中的需氧细菌、厌氧细菌、酵母菌和真菌
- 批准号:
10440741 - 财政年份:2021
- 资助金额:
$ 30.4万 - 项目类别:
Regulation of virulence in fungi under coculture condition with anaerobic bacteria
厌氧菌共培养条件下真菌毒力的调节
- 批准号:
21K07009 - 财政年份:2021
- 资助金额:
$ 30.4万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Polymicrobial interactions between commensal obligate anaerobic bacteria and cystic fibrosis pathogen P. aeruginosa
共生专性厌氧菌与囊性纤维化病原体铜绿假单胞菌之间的多种微生物相互作用
- 批准号:
10275319 - 财政年份:2021
- 资助金额:
$ 30.4万 - 项目类别:
Platform for the automated isolation and characterization of anaerobic bacteria
厌氧菌自动分离和表征平台
- 批准号:
445552570 - 财政年份:2020
- 资助金额:
$ 30.4万 - 项目类别:
Major Research Instrumentation
Development of therapy for triple negative breast cancer using anaerobic bacteria
利用厌氧菌开发三阴性乳腺癌疗法
- 批准号:
19K16452 - 财政年份:2019
- 资助金额:
$ 30.4万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Development of gene engineering method for anaerobic bacteria for efficient bio-hydrogen production
开发厌氧菌高效生物制氢的基因工程方法
- 批准号:
18K11708 - 财政年份:2018
- 资助金额:
$ 30.4万 - 项目类别:
Grant-in-Aid for Scientific Research (C)