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Directed evolution of multiple genomic loci allows the prediction of antibiotic resistance [Evolution]

Antibiotic development is frequently plagued by the rapid emergence of drug resistance. However, assessing the risk of resistance development in the preclinical stage is difficult. By building on multiplex automated genome engineering, we developed a method that enables precise mutagenesis of multiple, long genomic segments in multiple species without off-target modifications. Thereby, it enables the exploration of vast numbers of combinatorial genetic alterations in their native genomic context. This method is especially well-suited to screen the resistance profiles of antibiotic compounds. It allowed us to predict the evolution of resistance against antibiotics currently in clinical trials. We anticipate that it will be a useful tool to identify resistance-proof antibiotics at an early stage of drug development.

Authors:   Ákos Nyerges; Bálint Csörgő; Gábor Draskovits; Bálint Kintses; Petra Szili; Györgyi Ferenc; Tamás Révész; Eszter Ari; István Nagy; Balázs Bálint; Bálint Márk Vásárhelyi; Péter Bihari; Mónika Számel; Dávid Balogh; Henrietta Papp; Dorottya Kalapis; Balázs Papp; Csaba Pál
Journal:   Proceedings of the National Academy of Sciences current issue
Volume:   115
edition:   25
Year:   2018
Pages:   E5726
DOI:   10.1073/pnas.1801646115
Publication date:   19-Jun-2018
More about Proceedings of the National Academy of Sciences
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