a differential drug screen for compounds that select against antibiotic resistance一个微分药物筛选化合物选择对抗生素耐药性.pdfVIP

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a differential drug screen for compounds that select against antibiotic resistance一个微分药物筛选化合物选择对抗生素耐药性.pdf

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a differential drug screen for compounds that select against antibiotic resistance一个微分药物筛选化合物选择对抗生素耐药性

A Differential Drug Screen for Compounds That Select Against Antibiotic Resistance 1 2. 2. 1 1,3 Remy Chait , Shreya Shrestha , Aakash Kaushik Shah , Jean-Baptiste Michel , Roy Kishony * 1 Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, United States of America, 2 Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Cambridge, Massachusetts, United States of America, 3 School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, United States of America Abstract Antibiotics increase the frequency of resistant bacteria by providing them a competitive advantage over sensitive strains. Here, we develop a versatile assay for differential chemical inhibition of competing microbial strains, and use it to identify compounds that preferentially inhibit tetracycline-resistant relative to sensitive bacteria, thus ‘‘inverting’’ selection for resistance. Our assay distinguishes compounds selecting directly against specific resistance mechanisms and compounds whose selection against resistance is based on their physiological interaction with tetracycline and is more general with respect to resistance mechanism. A pilot screen indicates that both types of selection-inverting compounds are secreted by soil microbes, suggesting that nature has evolved a repertoire of chemicals that counteracts antibiotic resistance. Finally, we show that our assay can more generally permit simple, direct screening for drugs based on their differential activity against different strains or targets. Citation: Chait R, Shrestha S, Shah AK, Michel J-B, Kishony R (2010) A Differential Drug Screen for Compounds That Select