Antibiotic Resistance Platform

About

Background Solving the antibiotic resistance crisis requires the discovery of new antimicrobial drugs and the preservation of existing ones. With no new antibiotics on the horizon, blocking resistance with antibiotic adjuvants have emerged as a viable strategy. Antibiotics are co-formulated with an inhibitor of resistance, blocking the resistance element and freeing the antibiotic to target the bacterium. A major difficulty in identifying new antibiotics is the frequent rediscovery of known compounds, necessitating laborious “dereplication” to identify novel chemical entities. Researchers at McMaster University 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. Technology Overview The strength of the ARP lies within the mechanistic diversity and rigorously curated substrate specificity of the resistance strains. The platform consists of a cell-based library of Escherichia coli expressing individual resistance genes. Using either a low copy plasmid or integration of the gene into the bacterial chromosome, the researchers are able to control resistance gene copy number. Expression is further regulated through the use of two promoter systems differing in strength. This platform is optimized for antibiotic dereplication and the identification of potentiators of existing antibiotics. Further Details: https://www.ncbi.nlm.nih.gov/pubmed/28017602 Stage of Development: The minimal ARP kit is available for academic use.