High Throughput Screen for Inhibitors of Shigella Flexneri Dissemination
福氏志贺氏菌传播抑制剂的高通量筛选
基本信息
- 批准号:10404510
- 负责人:
- 金额:$ 59.77万
- 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:2020-06-01 至 2024-05-31
- 项目状态:已结题
- 来源:
- 关键词:ActinsAddressAffectAnimal ModelAntibiotic ResistanceAttentionAttenuatedBacteriaBiologicalBiological AssayBiological ProcessCell physiologyCellsCellular biologyCessation of lifeChemicalsColonComputer-Assisted Image AnalysisCytoskeletonCytosolDevelopmentDoseEpithelialEpithelial CellsFailureFluorescence MicroscopyFoundationsFutureGoalsHemorrhagic colitisHumanInfantIntestinal MucosaIntestinesInvadedLaboratoriesLeadLibrariesMembraneModelingOryctolagus cuniculusParentsPathogenesisPathway interactionsPatientsPharmaceutical ChemistryProcessResearch Project GrantsResolutionSeveritiesShigella InfectionsShigella flexneriSymptomsTestingTherapeutic InterventionTriageVaccinesVacuoleanalogbasecell motilitycellular targetingcytotoxicitydesigndisorder preventionhigh throughput screeninghuman modelin vivo Modelinhibitormedical countermeasuremicrobialpathogenpreclinical evaluationpreventpreventive interventionresistant strainscaffoldsmall moleculetherapeutic candidatetherapeutic lead compound
项目摘要
Abstract
Shigella flexneri is the leading cause of bacillary dysentery (bloody diarrhea) with 165 million cases per year
worldwide, including 1 million deaths. There is no vaccine currently available and the isolation of multiple
antibiotic resistant strains from patients worldwide is becoming the norm. S. flexneri pathogenesis relies on the
colonization of the human colon where the pathogen invades epithelial cells and spreads directly from cell to
cell through actin-based motility. Using an infant rabbit model of human shigellosis recently developed by our
group, we have discovered that the severity of the symptoms observed during bacillary dysentery, including
bloody diarrhea and destruction of the intestinal mucosa, correlates with the efficiency of S. flexneri
dissemination through cell-to-cell spread. Targeting the cellular pathways supporting S. flexneri dissemination
therefore represents a potential medical countermeasure for bacillary dysentery. Here, we propose to discover
small molecules that inhibit S. flexneri dissemination (Aim 1) and to prioritize the hit set based on chemical and
biological triage (Aim 2) and limited and exploratory medicinal chemistry (Aim 3).
摘要
福氏志贺菌是细菌性痢疾(血性腹泻)的主要原因,每年有1.65亿例病例
全世界,包括100万人死亡。目前没有疫苗可用,
来自全世界患者的抗生素耐药菌株正在成为常态。S.弗氏病的发病机制依赖于
在人类结肠的定殖中,病原体侵入上皮细胞并直接从细胞扩散到
细胞通过肌动蛋白为基础的运动。本研究利用我们最近建立的人志贺氏菌病幼兔模型,
组,我们发现,在细菌性痢疾期间观察到的症状的严重程度,包括
出血性腹泻和肠粘膜破坏与S.福氏
通过细胞间传播进行传播。靶向支持S.弗氏散布
因此是细菌性痢疾的潜在医学对策。在这里,我们建议发现
抑制S.福氏传播(目标1),并根据化学品和
生物分类(目标2)和有限和探索性药物化学(目标3)。
项目成果
期刊论文数量(0)
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会议论文数量(0)
专利数量(0)
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{{ truncateString('HERVE F AGAISSE', 18)}}的其他基金
Characterization of virulence factors in shigellosis
志贺氏菌病毒力因子的表征
- 批准号:
10724770 - 财政年份:2023
- 资助金额:
$ 59.77万 - 项目类别:
Characterization of an infant rabbit model of bacillary dysentery
幼兔细菌性痢疾模型的表征
- 批准号:
10203818 - 财政年份:2020
- 资助金额:
$ 59.77万 - 项目类别:
High Throughput Screen for Inhibitors of Shigella Flexneri Dissemination
福氏志贺氏菌传播抑制剂的高通量筛选
- 批准号:
10626880 - 财政年份:2020
- 资助金额:
$ 59.77万 - 项目类别:
High Throughput Screen for Inhibitors of Shigella Flexneri Dissemination
福氏志贺氏菌传播抑制剂的高通量筛选
- 批准号:
10029698 - 财政年份:2020
- 资助金额:
$ 59.77万 - 项目类别:
Characterization of an infant rabbit model of bacillary dysentery
幼兔细菌性痢疾模型的表征
- 批准号:
10055925 - 财政年份:2020
- 资助金额:
$ 59.77万 - 项目类别:
Characterization of vacuole escape in Shigella infection
志贺氏菌感染中液泡逃逸的特征
- 批准号:
9976031 - 财政年份:2020
- 资助金额:
$ 59.77万 - 项目类别:
Characterization of vacuole escape in Shigella infection
志贺氏菌感染中液泡逃逸的特征
- 批准号:
10088399 - 财政年份:2020
- 资助金额:
$ 59.77万 - 项目类别:
Regulation of bacterial pathogen actin-based motility by host cell kinases
宿主细胞激酶对细菌病原体肌动蛋白运动的调节
- 批准号:
8095076 - 财政年份:2011
- 资助金额:
$ 59.77万 - 项目类别:
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