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

Stokes, Jonathan M; Gutierrez, Arnaud; Lopatkin, Allison J; Andrews, Ian W; French, Shawn; Matic, Ivan; Brown, Eric D; Collins, James J · Nat Methods · 2019

basic_science · Level V

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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.

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