Rapid decline of bacterial drug-resistance in an antibiotic-free environment through phenotypic reversion

Abstract

Antibiotic resistance typically induces a fitness cost that shapes the fate of antibioticresistant bacterial populations. However, the cost of resistance can be mitigated by compensatory mutations elsewhere in the genome, and therefore the loss of resistance may proceed too slowly to be of practical importance. We present our study on the efficacy and phenotypic impact of compensatory evolution in Escherichia coli strains carrying multiple resistance mutations. We have demonstrated that drug-resistance frequently declines within 480 generations during exposure to an antibiotic-free environment. The extent of resistance loss was found to be generally antibioticspecific, driven by mutations that reduce both resistance level and fitness costs of antibioticresistance mutations. We conclude that phenotypic reversion to the antibiotic-sensitive state can be mediated by the acquisition of additional mutations, while maintaining the original resistance mutations. Our study indicates that restricting antimicrobial usage could be a useful policy, but for certain antibiotics only.