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Compounds that select against the tetracycline-resistance efflux pump

2016; Nature Portfolio; Volume: 12; Issue: 11 Linguagem: Inglês

10.1038/nchembio.2176

1552-4469

Laura K. Stone, Michael Baym, Tami D. Lieberman, Remy Chait, Jon Clardy, Roy Kishony,

Evolution and Genetic Dynamics

We developed a competition-based screening strategy to identify compounds that invert the selective advantage of antibiotic resistance. Using our assay, we screened over 19,000 compounds for the ability to select against the TetA tetracycline-resistance efflux pump in Escherichia coli and identified two hits, β-thujaplicin and disulfiram. Treating a tetracycline-resistant population with β-thujaplicin selects for loss of the resistance gene, enabling an effective second-phase treatment with doxycycline.