Evolutionary action of mutations reveals antimicrobial resistance genes in Escherichia coli.

ABSTRACT: Since antibiotic development lags, we search for potential drug targets through directed evolution experiments. A challenge is that many resistance genes hide in a noisy mutational background as mutator clones emerge in the adaptive population. Here, to overcome this noise, we quantify the impact of mutations through evolutionary action (EA). After sequencing ciprofloxacin or colistin resistance strains grown under different mutational regimes, we find that an elevated sum of the evolutionary action of mutations in a gene identifies known resistance drivers. This EA integration approach also suggests new antibiotic resistance genes which are then shown to provide a fitness advantage in competition experiments. Moreover, EA integration analysis of clinical and environmental isolates of anti

SUBMITTER: Marciano DC 

PROVIDER: S-EPMC9184624 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature