Non-monotonic Relationship between Mutation Rate and Speed of adaptation under Antibiotic Exposure in Escherichia coli

Abstract

The mutation is a fundamental source of biological evolution that create genetic variation in populations. Mutations can create new advantageous traits, but also potentially interfere with pre-existing organismal functions. Therefore, organisms may have evolved their mutation rates to appropriate levels to maintain or improve their fitness. In this study, we aimed to experimentally quantify the relationship between mutation rate and the speed of antibiotic resistance evolution. We conducted experimental evolution using twelve Escherichia coli mutator strains with increased mutation rates and five antibiotics. Our results showed that the highest mutation rate did not necessarily lead to the highest speed of adaptation, indicating a non-monotonic relationship between the speed of drug resistance evolution and mutation rate as expected. Moreover, this relationship was observed to differ among drugs, with significant differences in peak size observed between bacteriostatic and bactericidal antibiotics. We also successfully reproduced the mutation-rate dependence of the speed of adaptation using numerical simulation of a population dynamics model. These findings offer significant insights into the mutation rates evolution concomitant with the development of antibiotic resistance.