Assessing the impact of horizontal gene transfer on the evolution of antimicrobial resistance in Enterobacteriaceae

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The development of antimicrobial resistance (AMR) often incurs a fitness cost to the bacterial cell. Multiple AMR sometimes results in more, or less of a fitness cost than expected. This project is aimed at understanding this phenomenon, known as epistasis, specifically for clinically relevant resistances so we can determine optimal drug combinations for treatment of infectious disease.Proof of concept studies which would translate rapidly to evidence based treatment choice. We aim to determine antibiotic combinations which would lead to less fit, multiple resistant strains which would not persist in the environment once cessation of antibiotic treatment had occurred. Once reproducible evolutionary trajectories, based on drug resistance, had been identified we would aim to implement a change in clinical use to determine if background resistance to these drugs reduced.