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

Xiong, X.; Furseth, H.; McCoy, B.; Slavic, L.; Yuan, X.; Chen, S.; Baughn, A. D.; Minato, Y.; Harcombe, W. R.

2024-05-16 microbiology
10.1101/2024.05.15.594409 bioRxiv
Show 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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