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

• 批准号: 9155253
• 负责人: Bryan William Davies
• 金额: $ 41.72万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-15 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9155253
• 关键词: Acinetobacter baumannii; Affect; Amino Acid Substitution; Antibiotic Resistance; Antibiotics; Area; Back; Bacteria; Bacterial Infections; Cells; Chemicals; Chemistry; Data; Development; Escherichia coli; Event; Failure; Future; Goals; Individual; Klebsiella pneumonia bacterium; Knowledge; Literature; Lytic; Measures; Medical; Methods; Molecular; Molecular Target; Multi-Drug Resistance; Nature; Peptides; Physiological; Pilot Projects; Population; Preclinical Drug Evaluation; Process; Pseudomonas aeruginosa; Research; Resistance development; Slide; Specificity; Testing; Time; Translating; Tube; Work; antibiotic design; antimicrobial; antimicrobial drug; antimicrobial peptide; base; cost; fighting; high throughput screening; improved; microbial; next generation sequencing; novel; pathogen; prevent; protein aminoacid sequence; quantum; scaffold; screening; small molecule; synthetic biology; targeted treatment; therapeutic target

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比率持续上升，但我们开发新的抗菌药物 代理商停滞不前。新候选化合物的高失败率需要开发 发现新的抗菌剂的替代管道，以防止我们滑回前抗生素 医学时代我们的目标是开发和实施一种新的分子药物治疗方法， 筛选具有抗耐药性的抗微生物活性的肽化学的深入研究， 革兰氏阴性细菌病原体。我们的平台为单个细菌创造了微环境， 肽序列在生理相关条件下在混合细菌群体内相互作用。 使用下一代测序测量裂解事件，允许快速和批量筛选数百万个细胞。 一个试管中的肽。这一提议为抗菌肽研究提供了一个巨大的飞跃。 计划工作的完成预计将产生积极的翻译影响，大大扩大我们的 了解具有抗微生物活性的肽化学，并确定新的细菌治疗靶点 靶向，这两者都可能支持新的抗菌剂和方法的发展，以打击 耐药细菌。