Dynamics of Pseudomonas aeruginosa During Bacteremia
菌血症期间铜绿假单胞菌的动态
基本信息
- 批准号:10222524
- 负责人:
- 金额:$ 19.75万
- 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:2020-07-24 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAmplifiersAntibioticsAreaBackBacteremiaBacteriaBar CodesBloodBlood CirculationCaviaCellsCenters for Disease Control and Prevention (U.S.)Cessation of lifeCholecystectomyCommon bile duct structureDiseaseEtiologyFeedbackFoundationsFrequenciesGallbladderGastrointestinal tract structureHumanInfectionInterventionIntestinesKeratitisKnowledgeLibrariesLightLiverLungModelingMusMutationNosocomial InfectionsOral AdministrationOrganOutcomePathogenesisPathogenicityPneumoniaPopulationPrevalenceProcessPseudomonas aeruginosaReportingResistance to infectionSeedsSepsisSeveritiesSeverity of illnessSourceSpleenTailTestingTherapeutic AgentsVeinsattributable mortalityexperimental studyfitnessgastrointestinalgastrointestinal bacteriagenome sequencingimproved outcomemortalitymouse modelmultidrug-resistant Pseudomonas aeruginosanovelnovel therapeutic interventionnovel therapeuticsporcine modelpublic health prioritiesresistant strainwhole genome
项目摘要
Pseudomonas aeruginosa (PA) is the third most common gram-negative etiology of bloodstream infections,
and these infections are associated with a crude mortality rate of 39%. Despite their frequency and severity,
PA bloodstream infections are relatively poorly understood compared to pneumonia, burn infections, and
keratitis. To investigate the pathogenesis of PA bloodstream infections, we have used a mouse model in which
the tail vein is injected with a library of barcoded bacteria. Our preliminary experiments yielded several
unexpected findings. First, in approximately half of severely ill bacteremic mice, the PA bacteria found
disseminated throughout the body were descendants of just a few bacterial cells, suggesting that only a small
number of the PA in the initial inoculum persisted and disseminated to cause severe disease. Second, PA
bacteria in the blood migrated through a tight bottleneck to the gallbladder, which was a protective niche that
allowed for a small number of PA to replicate to extremely high numbers. From there, these descendants of
just a few PA bacteria seeded the intestines, presumably by passing through the common bile duct. This
finding is particularly interesting in the context of other reports suggesting that PA is capable of migrating from
the intestines to the bloodstream. Together, these observations suggest the intriguing hypothesis that spread
of PA from the bloodstream to the intestines and back to the bloodstream may generate a "positive feedback
loop" in which the gallbladder serves as an amplifier of PA numbers. In this application, we propose to address
this limitation and directly test our hypothesis by performing the following specific aims: (1) Characterize
bacterial dynamics over the course of PA bloodstream infections. (2) Determine whether interventions
that disrupt PA transit through the intestines improve outcomes in bloodstream infections. Completion
of these aims has the potential to uncover novel pathogenic mechanisms that contribute to the poor outcomes
observed in PA bloodstream infections. The impact of these studies is three-fold: (i) they may provide a
rationale for examining the pathogenesis of bloodstream infections caused by bacteria other than PA; (ii) the
knowledge gained may be used as a foundation and justification for costlier and more laborious studies in
humans with PA bloodstream infections; and (iii) these studies may inform novel therapeutic interventions that
lower the unacceptably high mortality rates currently associated with PA bacteremia.
铜绿假单胞菌(PA)是血液感染的第三大常见革兰氏阴性病因,
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Forest and Trees: Exploring Bacterial Virulence with Genome-wide Association Studies and Machine Learning.
- DOI:10.1016/j.tim.2020.12.002
- 发表时间:2021-07
- 期刊:
- 影响因子:15.9
- 作者:Allen JP;Snitkin E;Pincus NB;Hauser AR
- 通讯作者:Hauser AR
Taxonomic characterization of Pseudomonas hygromyciniae sp. nov., a novel species discovered from a commercially purchased antibiotic.
- DOI:10.1128/spectrum.01838-21
- 发表时间:2023-09-22
- 期刊:
- 影响因子:3.7
- 作者:Turner, Timothy L.;Mitra, Sumitra D.;Kochan, Travis J.;Pincus, Nathan B.;Lebrun-Corbin, Marine;Cheung, Bettina H.;Gatesy, Samuel W.;Afzal, Tania;Nozick, Sophie H.;Ozer, Egon A.;Hauser, Alan R.
- 通讯作者:Hauser, Alan R.
Genomics of Aminoglycoside Resistance in Pseudomonas aeruginosa Bloodstream Infections at a United States Academic Hospital.
美国学术医院铜绿假单胞菌血流感染的氨基糖苷耐药性基因组学。
- DOI:10.1128/spectrum.05087-22
- 发表时间:2023-06-15
- 期刊:
- 影响因子:3.7
- 作者:
- 通讯作者:
{{
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 }}
ALAN R HAUSER其他文献
ALAN R HAUSER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('ALAN R HAUSER', 18)}}的其他基金
Assessing SARS-CoV-2 Variant Evolution in Patients
评估患者中的 SARS-CoV-2 变异进化
- 批准号:
10426993 - 财政年份:2021
- 资助金额:
$ 19.75万 - 项目类别:
Dynamics of Pseudomonas aeruginosa During Bacteremia
菌血症期间铜绿假单胞菌的动态
- 批准号:
10042352 - 财政年份:2020
- 资助金额:
$ 19.75万 - 项目类别:
Systems Biology Modeling of Severe Hospital-Acquired Pneumonia
严重医院获得性肺炎的系统生物学模型
- 批准号:
10551467 - 财政年份:2018
- 资助金额:
$ 19.75万 - 项目类别:
Pathogen and Microbiome Temporal Changes During Resolution of HAP
HAP 消退过程中病原体和微生物组的时间变化
- 批准号:
10097985 - 财政年份:2018
- 资助金额:
$ 19.75万 - 项目类别:
相似海外基金
SBIR Phase II: Thermally-optimized power amplifiers for next-generation telecommunication and radar
SBIR 第二阶段:用于下一代电信和雷达的热优化功率放大器
- 批准号:
2335504 - 财政年份:2024
- 资助金额:
$ 19.75万 - 项目类别:
Cooperative Agreement
Interferometric and Multiband optical Parametric Amplifiers for Communications (IMPAC)
用于通信的干涉式和多频带光学参量放大器 (IMPAC)
- 批准号:
EP/X031918/1 - 财政年份:2024
- 资助金额:
$ 19.75万 - 项目类别:
Fellowship
Josephson Parametric Amplifiers using CVD graphene junctions
使用 CVD 石墨烯结的约瑟夫森参量放大器
- 批准号:
EP/Y003152/1 - 财政年份:2024
- 资助金额:
$ 19.75万 - 项目类别:
Research Grant
Semiconductor-based Terahertz Traveling Wave Amplifiers for Monolithic Integration
用于单片集成的半导体太赫兹行波放大器
- 批准号:
2329940 - 财政年份:2023
- 资助金额:
$ 19.75万 - 项目类别:
Standard Grant
OPTIME-PA: Optimal MMIC Design of E-Band Power Amplifiers for Satcom using Dedicated Measurements and Non-Linear Modelling
OPTIME-PA:使用专用测量和非线性建模的卫星通信 E 频段功率放大器的最佳 MMIC 设计
- 批准号:
10075892 - 财政年份:2023
- 资助金额:
$ 19.75万 - 项目类别:
Collaborative R&D
Optical Glass Amplifiers for High Capacity Networks
用于高容量网络的光学玻璃放大器
- 批准号:
538379-2018 - 财政年份:2022
- 资助金额:
$ 19.75万 - 项目类别:
Collaborative Research and Development Grants
Investigating the function of ZU5 domain-containing proteins as amplifiers of caspase activation
研究含有 ZU5 结构域的蛋白质作为 caspase 激活放大器的功能
- 批准号:
10681326 - 财政年份:2022
- 资助金额:
$ 19.75万 - 项目类别:
Investigating the function of ZU5 domain-containing proteins as amplifiers of caspase activation
研究含有 ZU5 结构域的蛋白质作为 caspase 激活放大器的功能
- 批准号:
10621402 - 财政年份:2022
- 资助金额:
$ 19.75万 - 项目类别:
Broadband Digital Doherty Amplifiers for Sub-6 GHz 5G wireless Applications
适用于 6 GHz 以下 5G 无线应用的宽带数字 Doherty 放大器
- 批准号:
573452-2022 - 财政年份:2022
- 资助金额:
$ 19.75万 - 项目类别:
Alliance Grants
TALENT – Tapered AmpLifiErs for quaNtum Technologies
人才 — 量子技术的锥形放大器
- 批准号:
10032436 - 财政年份:2022
- 资助金额:
$ 19.75万 - 项目类别:
Collaborative R&D














{{item.name}}会员




