Effects of Environment on Compensatory Mutations to Ameliorate Costs of Antibiotic Resistance

TLDR

Antibiotic resistance generally imposes a fitness cost that can be alleviated by second‑site mutations during evolution in hosts or laboratory media. The study investigates how the evolutionary environment—mice versus laboratory medium—affects the spectrum of fitness‑compensating mutations. Resistant bacteria were serially passaged in mice and in laboratory medium to identify the resulting compensatory mutations. The mutation spectra differed by environment, showing that compensatory evolution follows distinct trajectories inside versus outside a host.

Abstract

Most types of antibiotic resistance impose a biological cost on bacterial fitness. These costs can be compensated, usually without loss of resistance, by second-site mutations during the evolution of the resistant bacteria in an experimental host or in a laboratory medium. Different fitness-compensating mutations were selected depending on whether the bacteria evolved through serial passage in mice or in a laboratory medium. This difference in mutation spectra was caused by either a growth condition–specific formation or selection of the compensated mutants. These results suggest that bacterial evolution to reduce the costs of antibiotic resistance can take different trajectories within and outside a host.