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A multiplexable assay for screening antibiotic lethality against drug-tolerant bacteria

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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… Click to show full abstract

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.The solid media portable cell killing assay uses metabolism-sensitive staining to illuminate the killing of antibiotic-tolerant bacteria under resource-depleted conditions, thereby enabling multiplex, genome-scale analyses for the identification of target strains.

Keywords: tolerant bacteria; multiplexable assay; tolerant; drug tolerant; assay screening

Journal Title: Nature Methods
Year Published: 2019

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