Jonathan M. Stokes, Arnaud Gutierrez, Allison J. Lopatkin, Ian W. Andrews, Shawn French, Ivan Matic, Eric D. Brown & James J. Collins

Nature Methods (2019)

Antibiotic screens typically rely on growth inhibition to characterize compound bioactivity—an approach that cannot be used to assess the bactericidal activity of antibiotics against bacteria in drug-tolerant states. To address this limitation, we developed a multiplexed assay that uses metabolism-sensitive staining to report on the killing of antibiotic-tolerant bacteria. This method can be used with diverse bacterial species and applied to genome-scale investigations to identify therapeutic targets against tolerant pathogens.