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Targeting chronic Pseudomonas aeruginosa wound infections

针对慢性铜绿假单胞菌伤口感染

基本信息

批准号：
8509966
负责人：
Colin Manoil
金额：
$ 23.01万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-03-01 至 2015-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8509966
关键词：
Affect Anti-Bacterial Agents Antibiotics Bacteria Bacterial Infections Bacterial Proteins Biological Assay Biological Factors Chronic Diabetic mouse Diabetic wound Drug Targeting Expenditure Gene Fusion Gene Targeting Genetic Genome Goals Growth Healed Healthcare In Vitro Individual Infection LacZ Genes Libraries Mass Spectrum Analysis Medical Methodology Microbial Biofilms Modeling Mutation Oxidative Stress Phagocytes Phase Productivity Proteins Proteome Pseudomonas aeruginosa Reporter Reporter Genes Research Resistance Technology Testing Widespread Disease Work Wound Infection Xenorhabdus luminescens antimicrobial peptide base db/db mouse design diabetic effective therapy healing in vitro testing inhibitor/antagonist killings mouse model mutant novel pathogen public health relevance research study screening small molecule small molecule libraries therapeutic target tool wound

项目摘要

DESCRIPTION (provided by applicant): The proposed experiments aim to identify novel anti-bacterial drug targets for treatment of chronic wound infections and to carry out screens for small molecule inhibitors of several such targets. To accomplish this goal, we exploit three tools: 1) a newly developed diabetic mouse wound model in which healing is delayed due to a Pseudomonas aeruginosa biofilm infection, 2) a genome-scale genetic approach (Tn- seq) that can identify bacterial functions required for wound infection persistence, and 3) highly sensitive methodology employing mass spectrometry to identify proteins induced in wound infections that may include persistence functions missed by Tn-seq. Potential drug targets will be prioritized using a battery of tests thought to reflect infection. Screening strains designed to detect inhibitors of the three top targets will then be constructed and employed for screening a 200,000 chemical library.

描述（由申请人提供）：拟定实验旨在鉴定用于治疗慢性伤口感染的新型抗菌药物靶标，并筛选几种此类靶标的小分子抑制剂。为了实现这一目标，我们使用了三种工具： 1)新开发的糖尿病小鼠伤口模型，其中愈合由于铜绿假单胞菌生物膜感染而延迟，2）基因组规模的遗传方法（Tn-seq），其可以鉴定伤口感染持续性所需的细菌功能，和3）采用质谱法鉴定伤口感染中诱导的蛋白质的高灵敏度方法，其可以包括Tn-seq遗漏的持续性功能。潜在的药物靶点将优先使用一组被认为能反映感染的测试。然后将构建设计用于检测三个顶级靶标的抑制剂的筛选菌株，并用于筛选200，000个化学文库。