Directed evolution of multiple genomic loci allows the prediction of antibiotic resistance.

ABSTRACT: 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. Standard laboratory evolution approaches explore only a small fraction of the sequence space and fail to identify exceedingly rare resistance mutations and combinations thereof. Therefore, new rapid and exhaustive methods are needed to accurately assess the potential of resistance evolution and uncover the underlying mutational mechanisms. Here, we introduce directed evolution with random genomic mutations (DIvERGE), a method that allows an up to million-fold increase in mutation rate along the full lengths of multiple predefined loci in a range of bacterial species. In a single day, DIvERGE generated specific m

SUBMITTER: Nyerges A 

PROVIDER: S-EPMC6016788 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature