Compounds that select against the tetracycline resistance efflux pump

Abstract

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 E. 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.