Resistance Evolution in the Presence of Combination Antibiotic Therapy

Antimicrobial resistance (AMR) is a major global public health issue [1]. Antibiotic combination therapy is often used to prevent the spread of antibiotic resistance [2]. This presents a complex selection landscape for bacteria, with an interplay between mutation rates, fitness effects and epistasis determining the profile of the antibiotic resistant bacteria ultimately selected. This project will combine mathematical modelling with experimental analysis to explore resistance evolution within a pathogen group of importance in man and animals: the mycobacteria. The results will inform our understanding of the importance of heterogeneity in bacterial evolution but will also, ultimately, inform combination therapy design.