Context-dependent acquisition of antibiotic resistance mechanisms

The dramatic increase in antimicrobial resistance (AMR) forms a global challenge to public health. It is increasingly understood that the natural environment plays a key role in AMR evolution. Pharmaceutical residues and other pollutants in the environment such as metals can select for AMR. Moreover, largescale mixing of human-associated- and environmental bacteria can promote the exchange of resistance genes between strains, providing the genetic substrate for selection. Recent work suggests that such horizontal gene transfer might occur at the same rate as mutation but the relative importance of these two fundamentally distinct genetic mechanisms in generating AMR is not known. In this PhD project, we will design experiments to quantify and compare the prevalence of point mutations versus horizontal gene transfer events in generating resistance. Using flow cytometry and genome sequencing, we will measure the type and rate of genetic change under different realistic pollution scenarios. These data will provide fundamental data on bacterial genome evolution but also provide a scientific basis for pollution management.