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A duplexed CRISPRi-based approach to predict synergistic antibiotic targets in Escherichia coli.

Xianyi Xiong, Hannah Furseth, Brady McCoy, Lauren Slavic, Xun Feng YuaniD, Sydney Chen, Anthony D. BaughniD, Yusuke MinatoiD, William R. HarcombeiD

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Abstract

Co-repressing drug targets with CRISPR interference (CRISPRi) has the potential to predict both synergistic and additive drug combinations. In a screen experiment with Escherichia coli, pairwise gene co-repression assays correctly predicted the interaction type observed for 36 antibiotic pairs in checkerboard assays. Furthermore, we used this approach to identify promising synergistic interactions with a gene currently not targeted by clinical antibiotics. CRISPRi can systematically test the impact of gene inhibitions and identify novel drug targets.

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