Institute for Medical Engineering & Science, Department of Biological Engineering, and Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA, USA.
Infectious Disease and Microbiome Program, Broad Institute, Cambridge, MA, USA.
Nat Methods. 2019 Apr;16(4):303-306. doi: 10.1038/s41592-019-0333-y. Epub 2019 Mar 11.
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.
抗生素筛选通常依赖于生长抑制来描述化合物的生物活性——这种方法不能用于评估抗生素对处于药物耐受状态的细菌的杀菌活性。为了解决这一限制，我们开发了一种多重分析方法，该方法使用代谢敏感染色来报告抗生素耐受细菌的杀伤情况。这种方法可用于多种细菌物种，并可应用于全基因组研究，以确定针对耐受病原体的治疗靶点。
