Grant: Operating Grant

The initial optimism accompanying the introduction of antibiotic drugs to control infection over 60 years ago has been steadily eroded by growing reports of antimicrobial resistance in nearly all human-associated pathogens. What little faith remains in the long-term utility of antibiotics for treatment is now being undermined on a second front: resistance, once it evolves, is not readily lost when the offending antibiotic is removed from general use. The causes of persistence remain unresolved and form the subject of this proposal. The main objective of the work outlined here is to evaluate the hypothesis that the resistance mutations that most commonly arise in clinical settings actually pay little or no cost of resistance in the absence of antibiotic. Our work makes use of a combination of experimental, genomic and epidemiological approaches using resistance to quinolone antibiotics in two Pseudomonas species as a model. The results of this work will thus be crucial to designing strategies to eliminate or control resistance.