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Optimized methods for isolation and characterization of bacteriophage by VT-FACS

VT-FACS 噬菌体分离和表征的优化方法

基本信息

批准号：
10364653
负责人：
Natasha Jayna Sharp
金额：
$ 24.67万
依托单位：
GUILD ASSOCIATES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-04 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10364653
关键词：
Anti-Bacterial Agents Antibiotic Resistance Antibiotic Therapy Antibiotics Antimicrobial Resistance Archives Bacteria Bacterial Infections Bacteriophages Biological Sciences Cells Code Collection Computer software Consumption Cost Savings Coupled Custom Data Development Engineering Ensure Environment Formulation Future Goals Individual Infection Life Metagenomics Methodology Methods Microbial Biofilms Multi-Drug Resistance Mutate Outcomes Research Population Preparation Process Production Pseudomonas aeruginosa Research Support Residual state Resistance Sampling Sewage Source Stains System Techniques Technology Testing Therapeutic Time United States Viral Work antibiotic resistant infections antimicrobial antimicrobial drug antimicrobial resistant pathogen bacterial resistance base blind clinical application combat cost cost effective drug resistant pathogen effective therapy emerging pathogen experience global health improved innovation interest lytic replication multi-drug resistant pathogen pathogen pathogenic bacteria personalized medicine screening success virtual

项目摘要

Abstract Antibiotic-resistant (AMR) pathogens are emerging at alarming rates and current treatment options are becoming increasingly limited, expensive, and in some cases, nonexistent. Two million antibiotic resistant infections occur annually in the U.S and, although there is an urgent and immediate need for agents with activity against these emerging multidrug-resistant pathogens, only 2 new antibiotics have been approved since 2009. Therefore, the development of alternative antibacterial agents is crucial. A promising alternative to antibiotics is bacteriophage (phage) which have a natural ability to selectively infect and kill target bacteria. Phage is receiving renewed interest as a safe and effective therapy, but techniques for the isolation, characterization, production and testing of phages to identify ‘suitable’ phage cocktail candidates are time consuming, expensive and low throughput. Here we propose innovative high-throughput methodologies based on a proven VT-FACS platform which mitigate or circumvent these constraints providing time- and cost-savings in development and production of therapeutic phage cocktails. The goal of this project is further development of VT-FACS, a high-throughput phage isolation pipeline, to advance, characterize and support the use and rapid selection of phage as an alternative to classical antibiotics. Aim 1 will define and validate methods for screening and predicting likelihood of insolating pathogen- specific phage in prepared and archived lysates for informed on-demand selection. In Aim 2 we will use VT- FACS and adapt current workflow to identify the optimal bacterial host for production of the most inclusive and highest titer phage to minimize final cocktail complexity and production cost. Finally, Aim 3 will use VT-FACS to develop and validate high-throughput methods that isolate phage with antibiofilm activity. Through these 3 independent aims we will develop essential methods which each accelerate development and production of bacteriophage as an antibacterial therapy. For highest throughput and efficiency in a future working environment, the proposed methods can be applied in tandem, are inherently scalable and have potential to be automated. Successful completion of this work will provide expedited and cost-effective means to select and produce pathogen specific phage with the required host-range and secondary activities necessary for phage therapy. The ultimate outcome of the research supports improved and personalized phage therapy options to combat today’s urgent antibiotic resistance threat.

摘要