Platform for Discovering Antibiotics Targeting Gram Negative Pathogens

Kim Lewis of Northeastern University in the U.S. will lead a team that will develop an advanced platform to resolve intractable bottlenecks in antibiotic discovery. The focus will be on 30 targets in the cell envelope of Gram-negative bacteria. An AI-based search of genomic libraries for biosynthetic gene clusters associated with these targets produces candidate hits for isolation and also identifies producing taxa for selective capture of soil microbes. Encapsulating single cells from the environment in microdroplets obviates library construction. A pair of differently colored detector strains, susceptible/resistant to a compound hitting the desired target, identifies attractive hits at a test rate of 1,000,000/hour. Uncultured bacteria are incorporated into the screen, and the platform provides access to silent operons. Antibiotics discovered in this project will serve as a starting point for subsequent medicinal chemistry optimization.

This grant is funded by The Novo Nordisk Foundation.