Beta-lactamase fluorescent probes for bacterial detection

用于细菌检测的 β-内酰胺酶荧光探针

基本信息

  • 批准号:
    9309417
  • 负责人:
  • 金额:
    $ 58.42万
  • 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:
    2017-01-10 至 2020-12-31
  • 项目状态:
    已结题

项目摘要

Project Summary In September 2014, President Barack Obama signed an executive order directing federal resources to improve detection and prevention of antibiotic resistance, with a goal of developing a diagnostic test by 2020 that can distinguish between bacterial and viral infections in at least 20 min. The long-term goal of this research is to provide a novel platform solution for rapid, sensitive and specific detection of pathogenic bacterial infections through development of fluorescent probes specific to individual β-lactamases expressed in the bacteria. β-Lactamases are a class of bacterial hydrolases destroying β-lactam antibiotics and rendering antibiotics resistance in bacterial pathogens. Today many patients with suspected infections are administered antibiotics (most frequently β-lactams) empirically without prior proper identification of the causative agent, resulting in antibiotics overuse and overspread of antimicrobial resistance, with >500,000 deaths in the world annually attributable to these infections. This proposal will focus on two deadly bacteria: Mycobacterium tuberculosis (Mtb) and carbapenem-resistant Enterobacteriaceae (CRE). Tuberculosis represents one of the most dangerous respiratory pathogens in the history of mankind, killing over one million people each year and infecting one third of the world's population. Tubercle bacilli express BlaC, an Ambler class A β-lactamase, so Mtb has the intrinsic resistance to β-lactam antibiotics. Accumulating results including those from us have supported the use of BlaC as the biomarker for Mtb detection. Broad-spectrum carbapenem agents are frequently the last option for effective therapy of infections with antimicrobial resistant organisms, but the emergence of carbapenem-resistant Enterobacteriaceae (CRE) over the past decade has left clinicians with few treatment options. CRE is frequently due to the production of carbapenemase enzymes that efficiently hydrolyze carbapenems and other β-lactam antibiotics. This project will explore novel double-quenching, dual targeting probe design strategy to develop BlaC-specific substrate probes for rapid, highly sensitive Mtb detection (Aim #1) and carbapenemase-specific substrate probes for rapid, highly sensitive CRE detection (Aim #2). These new probes will be evaluated with clinical patient samples. The expected outcome of this research is that a series of novel fluorescent probes will be discovered as a novel assay platform to enable rapid, sensitive and specific detection of Mtb and CRE. We envision that these assays could reduce unnecessary healthcare costs associated with treatment of bacterial infection and prevent further expansion of existing drug-resistant strains.
项目摘要 2014年9月,美国总统奥巴马签署了一项行政命令,指示联邦资源改善 检测和预防抗生素耐药性,目标是到2020年开发一种诊断测试, 在至少20分钟内区分细菌和病毒感染。这项研究的长期目标是 为病原菌感染的快速、灵敏、特异检测提供了一种新的平台解决方案 通过开发特异于细菌中表达的单个β-内酰胺酶的荧光探针。 β-内酰胺酶是一类破坏β-内酰胺类抗生素并使抗生素降解的细菌水解酶 细菌病原体的耐药性。今天,许多疑似感染的患者都使用抗生素 (most通常是β-内酰胺类),而事先没有适当鉴定致病剂,导致 抗生素的过度使用和抗生素耐药性的过度传播,每年世界上有超过50万人死亡 这些感染的原因。 该提案将重点关注两种致命细菌:结核分枝杆菌(Mtb)和耐碳青霉烯类 肠杆菌科(CRE)。肺结核是世界上最危险的呼吸道病原体之一, 这是人类历史上最严重的疾病,每年造成100多万人死亡,感染世界三分之一的人口。 结核分枝杆菌表达Ambler A类β-内酰胺酶BlaC,因此Mtb对β-内酰胺具有内在耐药性 抗生素包括我们在内的累积结果支持使用BlaC作为生物标志物, 结核分枝杆菌检测。 广谱碳青霉烯类药物通常是有效治疗感染的最后选择, 抗生素耐药微生物,但碳青霉烯耐药肠杆菌科(CRE)的出现超过 过去的十年给临床医生留下了很少的治疗选择。CRE通常是由于生产 有效水解碳青霉烯类和其他β-内酰胺抗生素的碳青霉烯酶。 本项目将探索新的双淬灭、双靶向探针设计策略,开发BlaC特异性 用于快速、高灵敏度Mtb检测的底物探针(目标#1)和碳青霉烯酶特异性底物 用于快速、高灵敏度CRE检测的探针(目标#2)。这些新探头将通过临床评估 患者样本。 这项研究的预期成果是,一系列新的荧光探针将被发现,作为一种新的荧光探针。 新的检测平台,能够快速、灵敏和特异地检测结核分枝杆菌和CRE。我们设想这些 检测可以减少与治疗细菌感染相关的不必要的医疗费用, 进一步扩大现有的耐药菌株。

项目成果

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专利数量(2)

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Jianghong Rao其他文献

Jianghong Rao的其他文献

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{{ truncateString('Jianghong Rao', 18)}}的其他基金

PET tracer for imaging senescence
用于衰老成像的 PET 示踪剂
  • 批准号:
    10727823
  • 财政年份:
    2023
  • 资助金额:
    $ 58.42万
  • 项目类别:
Targeting apoptotic cells to enhance radiotherapy
靶向凋亡细胞以增强放射治疗
  • 批准号:
    10708827
  • 财政年份:
    2022
  • 资助金额:
    $ 58.42万
  • 项目类别:
Targeting apoptotic cells to enhance radiotherapy
靶向凋亡细胞以增强放射治疗
  • 批准号:
    10538071
  • 财政年份:
    2022
  • 资助金额:
    $ 58.42万
  • 项目类别:
Copper-depleting nanotheranostics for treating triple negative breast cancer
用于治疗三阴性乳腺癌的铜消耗纳米治疗剂
  • 批准号:
    10004020
  • 财政年份:
    2019
  • 资助金额:
    $ 58.42万
  • 项目类别:
Copper-depleting nanotheranostics for treating triple negative breast cancer
用于治疗三阴性乳腺癌的铜消耗纳米治疗剂
  • 批准号:
    10231101
  • 财政年份:
    2019
  • 资助金额:
    $ 58.42万
  • 项目类别:
Copper-depleting nanotheranostics for treating triple negative breast cancer
用于治疗三阴性乳腺癌的铜消耗纳米治疗剂
  • 批准号:
    10900851
  • 财政年份:
    2019
  • 资助金额:
    $ 58.42万
  • 项目类别:
Copper-depleting nanotheranostics for treating triple negative breast cancer
用于治疗三阴性乳腺癌的铜消耗纳米治疗剂
  • 批准号:
    10413265
  • 财政年份:
    2019
  • 资助金额:
    $ 58.42万
  • 项目类别:
Copper-depleting nanotheranostics for treating triple negative breast cancer
用于治疗三阴性乳腺癌的铜消耗纳米治疗剂
  • 批准号:
    10684918
  • 财政年份:
    2019
  • 资助金额:
    $ 58.42万
  • 项目类别:
Copper-depleting nanotheranostics for treating triple negative breast cancer
用于治疗三阴性乳腺癌的铜消耗纳米治疗剂
  • 批准号:
    10472523
  • 财政年份:
    2019
  • 资助金额:
    $ 58.42万
  • 项目类别:
Nanoparticle-Based Triple Modality Imaging and Photothermal Therapy of Brain Tumors
基于纳米颗粒的脑肿瘤三模态成像和光热疗法
  • 批准号:
    10000853
  • 财政年份:
    2016
  • 资助金额:
    $ 58.42万
  • 项目类别:

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Ecological and Evolutionary Drivers of Antibiotic Resistance in Patients
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