Speaker
Description
Resistance evolution is often described as an instantaneous event--the acquisition of a resistance mutation or a gene via horizontal transfer. However, in antibiotic fitness landscapes, this is often only the initial foothold on an adaptive peak, with many more steps required before reaching a fitness optimum. How important are these initial footholds for determining ultimate evolutionary outcomes on antibiotic fitness landscapes? Using fluoroquinolone-resistant Escherichia coli, we investigate how initial resistance mechanisms dictate how bacteria traverse antibiotic fitness landscapes, both under selection and genetic drift. We find that historical processes are a major driving force in dictating the potential for adaptation, with some regions of the landscape becoming accessible only to some foothold mutations. Unexpectedly, initial resistance mutations also differ in their robustness against the deleterious effects of mutation accumulation, suggesting that fitness landscapes around resistance mutations are rugged. We also investigate the connection between phylogeny and fitness in antibiotic fitness landscapes in clinical E. coli, which reveals a complex interplay between historical contingency and resistance alleles in determining fitness. Overall, our findings highlight the important role of historical contingency in determining how bacterial populations traverse fitness landscapes.
