Breath Test for Pseudomonas aeruginosa in CF

CF 中铜绿假单胞菌呼气试验

基本信息

  • 批准号:
    7571290
  • 负责人:
  • 金额:
    $ 18.75万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-07-17 至 2011-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The progressive lung damage in cystic fibrosis (CF) arises from characteristic bacterial colonization with Pseudomonas aeruginosa being central After initial infection then colonization with wild-type strains, conversion of P. aeruginosa to the mucoid phenotype in the CF host occurs, increasing bacterial resistance to antibiotics and inflammatory lung damage, and causing declining pulmonary function and prognosis. There remains an unmet need for rapid, non-invasive diagnostic analysis of lung P. aeruginosa presence, burden and mucoid status. Such a diagnostic would enable real-time monitoring of infection, and also significantly improve CF management, that currently relies upon indirect measures such as lung function and culture of expectorated sputum (that is variable, samples only a part of the lung, not applicable to younger patients) or broncoalveolar lavage (that is invasive and unsuitable for repetitive use). We show that several isotopically labeled substrates can be uniquely converted by P. aeruginosa to volatile exhalable labeled gasses, in ways that depend upon bacterial phenotype. We therefore hypothesize that We can use P. aeruginosa-specific metabolism of stable isotopically-labeled compounds to exhaled gasses to determine lung infection, bacterial load, biofilm growth and mucoid status However, before we move to a translational clinical trial, we need to test our hypothesis, delineate the typical ratios of labeled volatiles in wild-type, biofilm and mucoid strains, and also demonstrate effectiveness in an animal model of CF lung infection with P. aeruginosa. We will therefore perform these aims: Specific Aim 1 Demonstrate and develop use of isotope ratio mass spectrometry to measure isotopically labeled gasses from denitrification, cyanide synthase and urease activities in P. aeruginosa in vitro. Specific Aim 2 Delineate the range of ratios of urease to cyanide synthase/denitrification products for non- mucoid and mucoid P. aeruginosa strains in vitro growing planktonically and in biofilms. Specific Aim 3 Demonstrate effectiveness of this diagnostic approach in mice with mucoid and non-mucoid P. aeruginosa lung infection. Successful completion of this preclinical stage would be followed by formulation work on an inhaled dosage form, and Phase 1 clinical trial. PUBLIC HEALTH RELEVANCE: Cystic fibrosis is a high-prevalence, life shortening genetic disease, with much of the lung damage coming from infection with P. aeruginosa. Yet, the clinical tools to monitor for P. aeruginosa presence, burden & phenotype, so that the infection can be actively and pro-actively managed are not suitable or available. We propose to test the potential of a novel breath test, that relies upon a unique panel of P. aeruginosa metabolic pathways to produce stable isotope labeled gasses from specific substrates. If successful, this work can be translated to provide a sensitive and rapid new diagnostic that could significantly improve management of this disease.
描述(由申请人提供):囊性纤维化(CF)的进行性肺损伤是由以铜绿假单胞菌为中心的特征性细菌定植引起的,在初始感染后,被野生型菌株定植,铜绿假单胞菌在CF宿主体内向黏液型转化,细菌对抗生素的耐药性增加,炎症性肺损伤增加,导致肺功能和预后下降。对于肺铜绿假单胞菌的存在、负荷和黏液状态的快速、无创诊断分析仍然是一个未满足的需求。这样的诊断将能够实时监测感染,并显著改善CF的管理,目前CF的管理依赖于间接措施,如肺功能和痰培养(这是可变的,仅采集肺的一部分,不适用于年轻患者)或支气管滤泡灌洗(这是侵入性的,不适合重复使用)。我们表明,几种同位素标记的底物可以被铜绿假单胞菌独特地转化为挥发性可呼出的标记气体,其方式取决于细菌表型。因此,我们假设我们可以利用P. aeruginosa对稳定同位素标记化合物的特异性代谢来确定肺部感染、细菌负荷、生物膜生长和粘液状态。然而,在我们进入转化临床试验之前,我们需要验证我们的假设,描述野生型、生物膜和粘液菌株中标记挥发物的典型比例,并在P. aeruginosa CF肺部感染的动物模型中证明有效性。因此,我们将实现这些目标:具体目标1:演示和开发同位素比质谱法的使用,以测量铜绿假单胞菌体外反硝化过程中同位素标记的气体、氰化物合成酶和脲酶的活性。明确非黏液性和黏液性铜绿假单胞菌在体外浮游生长和生物膜中脲酶与氰化物合成酶/反硝化产物的比值范围。特异性目的3证明这种诊断方法在粘液样和非粘液样铜绿假单胞菌肺部感染小鼠中的有效性。成功完成临床前阶段后,将进行吸入剂型的配方工作和1期临床试验。公共卫生相关性:囊性纤维化是一种高患病率、缩短寿命的遗传性疾病,大部分肺损伤来自铜绿假单胞菌感染。然而,监测铜绿假单胞菌存在、负担和表型,从而对感染进行积极主动管理的临床工具尚不合适或缺乏。我们建议测试一种新型呼吸测试的潜力,这种测试依赖于一组独特的铜绿假单胞菌代谢途径,从特定的底物中产生稳定的同位素标记气体。如果成功,这项工作可以转化为提供一种敏感和快速的新诊断,可以显着改善这种疾病的管理。

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(1)

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 }}

GRAHAM S TIMMINS其他文献

GRAHAM S TIMMINS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('GRAHAM S TIMMINS', 18)}}的其他基金

Rifampin potentiation in NTM
利福平在 NTM 中的增强作用
  • 批准号:
    9908969
  • 财政年份:
    2020
  • 资助金额:
    $ 18.75万
  • 项目类别:
Reversing Isoniazid Resistance By Isotopic Substitution
通过同位素替代逆转异烟肼耐药性
  • 批准号:
    9347156
  • 财政年份:
    2017
  • 资助金额:
    $ 18.75万
  • 项目类别:
Pyrazinamide Breath Test for TB
吡嗪酰胺呼气试验检测结核病
  • 批准号:
    8870819
  • 财政年份:
    2015
  • 资助金额:
    $ 18.75万
  • 项目类别:
Breath Test for Pseudomonas aeruginosa in CF
CF 中铜绿假单胞菌呼气试验
  • 批准号:
    7895581
  • 财政年份:
    2009
  • 资助金额:
    $ 18.75万
  • 项目类别:
Nanostructured in vitro TB latency model
纳米结构体外结核潜伏期模型
  • 批准号:
    7876788
  • 财政年份:
    2009
  • 资助金额:
    $ 18.75万
  • 项目类别:
Nanostructured in vitro TB latency model
纳米结构体外结核潜伏期模型
  • 批准号:
    7737798
  • 财政年份:
    2009
  • 资助金额:
    $ 18.75万
  • 项目类别:
Molecular Surrogate for Melanoma Prevention
预防黑色素瘤的分子替代品
  • 批准号:
    7383595
  • 财政年份:
    2007
  • 资助金额:
    $ 18.75万
  • 项目类别:
Molecular Surrogate for Melanoma Prevention
预防黑色素瘤的分子替代品
  • 批准号:
    7501411
  • 财政年份:
    2007
  • 资助金额:
    $ 18.75万
  • 项目类别:
MOLECULAR IMAGING OF MELANOMA BY EPR
通过 EPR 进行黑色素瘤分子成像
  • 批准号:
    7048244
  • 财政年份:
    2006
  • 资助金额:
    $ 18.75万
  • 项目类别:
Antimycobacterial NO from KatG Activation of Isoniazid
KatG 激活异烟肼的抗分枝杆菌 NO
  • 批准号:
    7230267
  • 财政年份:
    2006
  • 资助金额:
    $ 18.75万
  • 项目类别:

相似海外基金

Quantification of Neurovasculature Changes in a Post-Hemorrhagic Stroke Animal-Model
出血性中风后动物模型中神经血管变化的量化
  • 批准号:
    495434
  • 财政年份:
    2023
  • 资助金额:
    $ 18.75万
  • 项目类别:
Small animal model for evaluating the impacts of cleft lip repairing scar on craniofacial growth and development
评价唇裂修复疤痕对颅面生长发育影响的小动物模型
  • 批准号:
    10642519
  • 财政年份:
    2023
  • 资助金额:
    $ 18.75万
  • 项目类别:
Bioactive Injectable Cell Scaffold for Meniscus Injury Repair in a Large Animal Model
用于大型动物模型半月板损伤修复的生物活性可注射细胞支架
  • 批准号:
    10586596
  • 财政年份:
    2023
  • 资助金额:
    $ 18.75万
  • 项目类别:
A Comparison of Treatment Strategies for Recovery of Swallow and Swallow-Respiratory Coupling Following a Prolonged Liquid Diet in a Young Animal Model
幼年动物模型中长期流质饮食后吞咽恢复和吞咽呼吸耦合治疗策略的比较
  • 批准号:
    10590479
  • 财政年份:
    2023
  • 资助金额:
    $ 18.75万
  • 项目类别:
Diurnal grass rats as a novel animal model of seasonal affective disorder
昼夜草鼠作为季节性情感障碍的新型动物模型
  • 批准号:
    23K06011
  • 财政年份:
    2023
  • 资助金额:
    $ 18.75万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Longitudinal Ocular Changes in Naturally Occurring Glaucoma Animal Model
自然发生的青光眼动物模型的纵向眼部变化
  • 批准号:
    10682117
  • 财政年份:
    2023
  • 资助金额:
    $ 18.75万
  • 项目类别:
A whole animal model for investigation of ingested nanoplastic mixtures and effects on genomic integrity and health
用于研究摄入的纳米塑料混合物及其对基因组完整性和健康影响的整体动物模型
  • 批准号:
    10708517
  • 财政年份:
    2023
  • 资助金额:
    $ 18.75万
  • 项目类别:
A Novel Large Animal Model for Studying the Developmental Potential and Function of LGR5 Stem Cells in Vivo and in Vitro
用于研究 LGR5 干细胞体内外发育潜力和功能的新型大型动物模型
  • 批准号:
    10575566
  • 财政年份:
    2023
  • 资助金额:
    $ 18.75万
  • 项目类别:
Elucidating the pathogenesis of a novel animal model mimicking chronic entrapment neuropathy
阐明模拟慢性卡压性神经病的新型动物模型的发病机制
  • 批准号:
    23K15696
  • 财政年份:
    2023
  • 资助金额:
    $ 18.75万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
The effect of anti-oxidant on swallowing function in an animal model of dysphagia
抗氧化剂对吞咽困难动物模型吞咽功能的影响
  • 批准号:
    23K15867
  • 财政年份:
    2023
  • 资助金额:
    $ 18.75万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了