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

抗菌素耐药性（AMR）的发展通常会导致细菌细胞的适应性成本。多重AMR有时会导致比预期更多或更少的适应度成本。该项目旨在了解这种被称为上位的现象，特别是与临床相关的耐药性，以便我们能够确定治疗传染病的最佳药物组合。概念证明研究将迅速转化为基于证据的治疗选择。我们的目标是确定抗生素组合，这将导致不太适合，多重耐药菌株不会在环境中持续存在，一旦停止抗生素治疗发生。一旦确定了基于耐药性的可重复进化轨迹，我们将致力于在临床应用中实施改变，以确定对这些药物的背景耐药性是否减少。

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.