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: 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
• 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

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.

项目总结。

项目成果

TsrA Regulates Virulence and Intestinal Colonization in Vibrio cholerae.

• DOI: 10.1128/msphere.01014-20
• 发表时间: 2020-12-09
• 期刊: mSphere
• 影响因子: 4.8
• 作者: DuPai CD;Cunningham AL;Conrado AR;Wilke CO;Davies BW
• 通讯作者: Davies BW

Desiccation Tolerance Assays for Acinetobacter baumannii.

鲍曼不动杆菌的干燥耐受性测定。

• DOI: 10.1007/978-1-4939-9118-1_18
• 发表时间: 2019
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Wang,Xun;Trent,MStephen;Davies,BryanW
• 通讯作者: Davies,BryanW