Recording the role of persisters in infection relapse

记录持续者在感染复发中的作用

基本信息

  • 批准号:
    10592618
  • 负责人:
  • 金额:
    $ 25.43万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-11-08 至 2024-10-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Beside the well‐researched antibiotic resistance, bacterial pathogens can survive antibiotic exposure through drug persistence. Persistence has been more difficult to study because of the transiency of the phenomenon, where some bacteria arrest growth, thus surviving several antibiotics. Resumption of growth by persister is thought to account for infection relapses but this has never been directly tested or demonstrated. With this proposal, we aim at answering the fundamental question: are persisters the future “relapsors” and thereby constitute a real reservoir for relapse of infections? In this project, we will make use of a remarkably useful model intracellular pathogen, Salmonella enterica serovar Typhimurium to establish whether Salmonella persisters are directly responsible for infection relapse. This proposal leverages further the development by our lab of model systems and tools to track persisters in the context of infection. First, in Aim 1 of this project, we will adapt a CRISPR‐based recorder that we recently built in the lab to record in the bacterial genome of persisters the state of growth‐arrest, thus leaving an indelible genetic scar in CRISPR arrays that is perpetuated and detectable in their progeny. We will further characterize this tool during infection of primary murine macrophages to determine if, in addition to recording growth arrest, it can also be used as recorder of length of growth arrest. We will also adapt pSCRATCH to record other signals in addition to growth arrest. Then, in Aim 2, we will use the growth‐arrest recorder to assess for Salmonella, for the first time, whether persisters are the direct reservoir for bacterial regrowth during relapse. This Aim will enable us to determine where relapsors originate from, from growth‐arrested persisters or few growers not eradicated by the drugs for other reasons, such as lack of antibiotic accessibility. It is of the utmost importance to determine whether persisters are the major source of infecting bacteria during relapse in order to efficiently target persistent infections with improved therapeutics and counteract the generation of antibiotic resistance.
项目摘要 除了经过充分研究的抗生素耐药性外,细菌病原体可以通过以下方式在抗生素暴露中存活下来: 药物持久性持久性更难研究,因为这种现象是短暂的, 其中一些细菌抑制生长,从而在几种抗生素中存活。恢复增长由persister是 被认为是感染复发的原因,但这从未被直接测试或证明。与此 我们的建议旨在回答一个基本问题:坚持者是未来的“复发者”, 是否构成了感染复发的真实的宿主?在这个项目中,我们将使用一个非常有用的模型 细胞内病原体,沙门氏菌血清型鼠伤寒,以确定是否沙门氏菌持久 直接导致感染复发。该提案进一步利用了我们实验室的模型开发 系统和工具来跟踪感染背景下的持久性。首先,在本项目的目标1中,我们将采用 我们最近在实验室中建立的基于CRISPR的记录器,用于记录持续存在的细菌基因组中的状态 因此,在CRISPR阵列中留下了不可磨灭的遗传疤痕,这种疤痕在体内永久存在并可检测到。 他们的后代我们将在感染原代鼠巨噬细胞期间进一步表征该工具, 确定除了记录生长停滞之外,它是否还可以用作生长停滞长度的记录器。 我们还将调整pSCRATCH以记录除生长停滞之外的其他信号。在目标2中,我们将使用 生长停滞记录仪首次评估沙门氏菌是否是直接储存库 复发时细菌的再生这一目标将使我们能够确定复发者的来源, 生长停滞的坚持者或少数种植者因其他原因(如缺乏抗生素)而未被药物根除 可访问性。确定持久性病原体是否为主要传染源至关重要 为了用改进的治疗剂有效地靶向持续性感染, 抑制抗生素耐药性的产生。

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 }}

Sophie Helaine其他文献

Sophie Helaine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('Sophie Helaine', 18)}}的其他基金

The physiological activation and consequences of Toxin-Antitoxin systems in Salmonella
沙门氏菌毒素-抗毒素系统的生理激活和后果
  • 批准号:
    10418802
  • 财政年份:
    2021
  • 资助金额:
    $ 25.43万
  • 项目类别:
The physiological activation and consequences of Toxin-Antitoxin systems in Salmonella
沙门氏菌毒素-抗毒素系统的生理激活和后果
  • 批准号:
    10295585
  • 财政年份:
    2021
  • 资助金额:
    $ 25.43万
  • 项目类别:
The physiological activation and consequences of Toxin-Antitoxin systems in Salmonella
沙门氏菌毒素-抗毒素系统的生理激活和后果
  • 批准号:
    10621790
  • 财政年份:
    2021
  • 资助金额:
    $ 25.43万
  • 项目类别:

相似海外基金

SBIR Phase II: Development of a urine dipstick test that can guide immediate and appropriate antibiotic therapy for treatment of complicated urinary tract infections
SBIR II 期:开发尿液试纸测试,可以指导复杂尿路感染的立即和适当的抗生素治疗
  • 批准号:
    2213034
  • 财政年份:
    2023
  • 资助金额:
    $ 25.43万
  • 项目类别:
    Cooperative Agreement
Personalized Antibiotic Therapy in the Emergency Department: PANTHER Trial
急诊科的个性化抗生素治疗:PANTHER 试验
  • 批准号:
    10645528
  • 财政年份:
    2023
  • 资助金额:
    $ 25.43万
  • 项目类别:
Strategies for improving the efficacy of combinatorial antibiotic therapy in chronic infections
提高慢性感染联合抗生素治疗疗效的策略
  • 批准号:
    10736285
  • 财政年份:
    2023
  • 资助金额:
    $ 25.43万
  • 项目类别:
A Novel Bone Targeted Antibiotic Therapy for the Treatment of Infected Fractures
一种治疗感染性骨折的新型骨靶向抗生素疗法
  • 批准号:
    10603486
  • 财政年份:
    2023
  • 资助金额:
    $ 25.43万
  • 项目类别:
Severe Cutaneous Adverse Reactions Following Outpatient Antibiotic Therapy: A Population-based Study
门诊抗生素治疗后的严重皮肤不良反应:一项基于人群的研究
  • 批准号:
    449379
  • 财政年份:
    2020
  • 资助金额:
    $ 25.43万
  • 项目类别:
    Studentship Programs
Sex-Specific Differences in End-of-Life Burdensome Interventions and Antibiotic Therapy in Nursing Home Residents With Advanced Dementia
患有晚期痴呆症的疗养院居民的临终干预和抗生素治疗的性别差异
  • 批准号:
    422034
  • 财政年份:
    2020
  • 资助金额:
    $ 25.43万
  • 项目类别:
Optimizing outpatient parenteral antibiotic therapy to support hospital-in-the-home program across the unique environmental conditions of Australia
优化门诊肠外抗生素治疗,以支持澳大利亚独特环境条件下的家庭医院计划
  • 批准号:
    nhmrc : 1197866
  • 财政年份:
    2020
  • 资助金额:
    $ 25.43万
  • 项目类别:
    Investigator Grants
Resistance evolution in the presence of combination antibiotic therapy
联合抗生素治疗下耐药性的演变
  • 批准号:
    2241853
  • 财政年份:
    2019
  • 资助金额:
    $ 25.43万
  • 项目类别:
    Studentship
Host-pathogen interactions in antibiotic therapy for listeriosis
李斯特菌病抗生素治疗中宿主与病原体的相互作用
  • 批准号:
    18K07106
  • 财政年份:
    2018
  • 资助金额:
    $ 25.43万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Multipurpose targeted nano-antibiotic therapy to fight tough infection in bones
多用途靶向纳米抗生素疗法可对抗骨骼中的严重感染
  • 批准号:
    9788269
  • 财政年份:
    2018
  • 资助金额:
    $ 25.43万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了