Dominant resistance and negative epistasis can limit the co-selection of de novo resistance mutations and antibiotic resistance genes.

ABSTRACT: To tackle the global antibiotic resistance crisis, antibiotic resistance acquired either vertically by chromosomal mutations or horizontally through antibiotic resistance genes (ARGs) have been studied. Yet, little is known about the interactions between the two, which may impact the evolution of antibiotic resistance. Here, we develop a multiplexed barcoded approach to assess the fitness of 144 mutant-ARG combinations in Escherichia coli subjected to eight different antibiotics at 11 different concentrations. While most interactions are neutral, we identify significant interactions for 12% of the mutant-ARG combinations. The ability of most ARGs to confer high-level resistance at a low fitness cost shields the selective dynamics of mutants at low drug concentrations. Therefore, high-fitne

SUBMITTER: Porse A 

PROVIDER: S-EPMC7057998 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature