A High-Throughput Molecular Platform for Antimicrobial Discovery and Study

用于抗菌药物发现和研究的高通量分子平台

基本信息

批准号：
9923526
负责人：
Bryan William Davies
金额：
$ 40.44万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-15 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9923526
关键词：
Acinetobacter baumannii Affect Amino Acid Substitution Antibiotic Resistance Antibiotics Area Back Bacteria Bacterial Antibiotic Resistance Bacterial Infections Cells Chemicals Chemistry Data Development Drug Screening Escherichia coli Event Failure Future Goals Individual Klebsiella pneumoniae Knowledge Literature Lytic Measures Medical Methods Molecular Molecular Target Multi-Drug Resistance Nature Peptides Physiological Pilot Projects Population Process Pseudomonas aeruginosa Research Resistance development Slide Specificity Testing Therapeutic Time Tube Work antibiotic design antimicrobial antimicrobial drug antimicrobial peptide base cost fighting high throughput screening improved microbial next generation sequencing novel pathogenic bacteria prevent protein aminoacid sequence quantum scaffold screening small molecule synthetic biology targeted treatment therapeutic target translational impact

项目摘要

Project Summary. While rates of antibiotic resistance bacterial infections continue to rise, our development of new antimicrobial agents has stagnated. The high failure rate of new candidate compounds demands the development of alternative pipelines for the discovery of new antimicrobial agents to prevent our slide back to the pre-antibiotic medical era. Our objective in this proposal is to develop and implement a new molecular approach to drug screening for an in-depth study of peptide chemistry with antimicrobial activity against antibiotic-resistant, Gram-negative bacterial pathogens. Our platform creates microenvironments for individual bacteria and peptide sequences to interact under physiologically relevant conditions, within a mixed bacterial population. Lytic events are measured using next-generation sequencing, allowing rapid and batch screening of millions of peptides in one tube. This proposal offers a quantum leap forward in antimicrobial peptide research. Completion of the planned work is expected to have a positive translational impact by greatly expanding our understanding of peptide chemistry with antimicrobial activity and identify new bacterial targets for therapeutic targeting, both of which will likely support the development of new antimicrobials and approaches to fight antibiotic-resistant bacteria.

项目摘要。虽然抗生素耐药性细菌感染的发生率继续升高，但我们的新抗菌剂发展代理人停滞不前。新候选人化合物的高失败率需要开发发现新抗菌剂的替代管道，以防止我们的滑动回到抗生素前医学时代。我们在此提案中的目标是开发和实施一种新的分子方法筛查对肽化学的深入研究，其抗生素抗生素的抗菌活性，革兰氏阴性细菌病原体。我们的平台为单个细菌和在混合细菌种群中，在生理相关条件下相互作用的肽序列。裂解事件是使用下一代测序测量的，可以快速筛选数百万一根管中的肽。该提案在抗菌肽研究中提供了量子飞跃。预计计划中的工作将通过大大扩展我们的了解具有抗菌活性的肽化学，并确定治疗的新细菌靶标针对目标，两者都可能支持开发新的抗微生物和战斗方法抗生素耐药菌。