Discovery of Next-Generation Antimicrobials through Bacterial Self-Screening of Surface-Displayed Peptide Libraries
| Autor: | Cory D. DuBois, Gregory A. Knauf, Claus O. Wilke, Sean P. Leonard, Bryan William Davies, Ashley L. Cunningham, Ashley T. Tucker, M. Stephen Trent |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification Antimicrobial peptides Peptide Computational biology Biology Antimicrobial Article General Biochemistry Genetics and Molecular Biology Anti-Bacterial Agents High-Throughput Screening Assays Single tube Mice 03 medical and health sciences 030104 developmental biology Antibiotic resistance chemistry Peptide Library Drug Discovery Escherichia coli Animals Self screening Function (biology) |
| Zdroj: | Cell. 172:618-628.e13 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2017.12.009 |
| Popis: | Summary Peptides have great potential to combat antibiotic resistance. While many platforms can screen peptides for their ability to bind to target cells, there are virtually no platforms that directly assess the functionality of peptides. This limitation is exacerbated when identifying antimicrobial peptides because the phenotype, death, selects against itself and has caused a scientific bottleneck that confines research to a few naturally occurring classes of antimicrobial peptides. We have used this seeming dissonance to develop Surface Localized Antimicrobial Display (SLAY), a platform that allows screening of unlimited numbers of peptides of any length, composition, and structure in a single tube for antimicrobial activity. Using SLAY, we screened ∼800,000 random peptide sequences for antimicrobial function and identified thousands of active sequences, dramatically increasing the number of known antimicrobial sequences. SLAY hits present with different potential mechanisms of peptide action and access to areas of antimicrobial physicochemical space beyond what nature has evolved. Video Abstract |
| Databáze: | OpenAIRE |
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