Antimicrobial resistance is acquired via mutations and/or mobile genetic elements (plasmids and transposons), containing antibiotic resistance genes.
These mutations and acquired antimicrobial resistance genes can have differing impacts on bacterial fitness (the ability of a bacterium to grow). Multiple mutations and/or mobile genetic elements can interact and alter the fitness landscape of the cell, a process termed epistasis. Additionally these fitness effects are often alleviated via further, compensatory, mutations within the cell. This in turn can lead to collateral sensitivity effects where the development of resistance to one antibiotic alters the sensitivity to another.
We use an in vitro experimental evolutionary approach supported by whole genome sequencing and comparative genomics to characterize these evolutionary trajectories and interactions with the aim of translating these findings into policy and treatment decisions and optimizing the use of antimicrobials in clinical practice.
Currently this work is funded by the MRC and the NIHR.