title: A Common Platform for Antibiotic Dereplication and Adjuvant Discovery.
abstract: Solving the antibiotic resistance crisis requires the discovery of new antimicrobial drugs and the preservation of existing ones. The discovery of inhibitors of antibiotic resistance, antibiotic adjuvants, is a proven example of the latter. A major difficulty in identifying new antibiotics is the frequent rediscovery of known compounds, necessitating laborious "dereplication" to identify novel chemical entities. We have developed an antibiotic resistance platform (ARP) that can be used for both the identification of antibiotic adjuvants and for antibiotic dereplication. The ARP is a cell-based array of mechanistically distinct individual resistance elements in an identical genetic background. In dereplication mode, we demonstrate the rapid identification, and thus discrimination, of common antibiotics. In adjuvant discovery mode, we show that the ARP can be harnessed in screens to identify inhibitors of resistance. The ARP is therefore a powerful tool that has broad application in confronting the resistance crisis.
authors.affiliation: Department of Biochemistry and Biomedical Sciences, M.G. DeGroote Institute for Infectious Disease Research, DeGroote School of Medicine, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4K1, Canada.
authors.forename: Georgina
authors.initials: G
authors.lastname: Cox
authors.affiliation: Department of Biochemistry and Biomedical Sciences, M.G. DeGroote Institute for Infectious Disease Research, DeGroote School of Medicine, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4K1, Canada.
authors.forename: Arthur
authors.initials: A
authors.lastname: Sieron
authors.affiliation: Department of Biochemistry and Biomedical Sciences, M.G. DeGroote Institute for Infectious Disease Research, DeGroote School of Medicine, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4K1, Canada.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: King
authors.affiliation: Department of Biochemistry and Biomedical Sciences, M.G. DeGroote Institute for Infectious Disease Research, DeGroote School of Medicine, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4K1, Canada.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: De Pascale
authors.affiliation: Department of Biochemistry and Biomedical Sciences, M.G. DeGroote Institute for Infectious Disease Research, DeGroote School of Medicine, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4K1, Canada.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Pawlowski
authors.affiliation: Department of Biochemistry and Biomedical Sciences, M.G. DeGroote Institute for Infectious Disease Research, DeGroote School of Medicine, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4K1, Canada.
authors.forename: Kalinka
authors.initials: K
authors.lastname: Koteva
authors.affiliation: Department of Biochemistry and Biomedical Sciences, M.G. DeGroote Institute for Infectious Disease Research, DeGroote School of Medicine, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4K1, Canada. Electronic address: wrightge@mcmaster.ca.
authors.forename: Gerard D
authors.initials: GD
authors.lastname: Wright
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D055808:Drug Discovery; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D057166:High-Throughput Screening Assays; D015394:Molecular Structure
chemical_list: D000277:Adjuvants, Pharmaceutic; D000900:Anti-Bacterial Agents
keywords: adjuvant; antibiotic; antibiotic resistance; dereplication; natural products; potentiation