Compounds that select against the tetracycline-resistance efflux pump Journal Article


Author(s): Stone, Laura K; Baym, Michael; Lieberman, Tami D; Chait, Remy; Clardy, Jon C; Kishony, Roy K
Article Title: Compounds that select against the tetracycline-resistance efflux pump
Affiliation IST Austria
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 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.
Journal Title: Nature Chemical Biology
Volume: 12
Issue 11
ISSN: 1552-4469
Publisher: Nature Publishing Group  
Date Published: 2016-11-01
Start Page: 902
End Page: 904
DOI: 10.1038/nchembio.2176
Notes: This work was supported in part by National Institute of Allergy and Infectious Diseases grant U54 AI057159, US National Institutes of Health grants R01 GM081617 (to R.K.) and GM086258 (to J.C.), European Research Council FP7 ERC grant 281891 (to R.K.) and a National Science Foundation Graduate Fellowship (to L.K.S.).
Open access: no