Speaker
Description
It became clear shortly after the discovery of the first antibiotics that bacteria are able to survive and evade antibiotic treatment. Ever since, understanding the emergence of antimicrobial resistance is of great interest and a large number of studies have addressed the mechanisms of bacterial evolution in the presence of antibiotics. However, such studies often focus exclusively on antibiotic resistance, while other effects such as tolerance and persistence evolution remain poorly understood. Here, we present a theoretical framework to describe the decline and recovery of a bacterial population under periodic antibiotic stress. Based on a well established model of Dose Response Curves, we define an effective fitness measure that quantifies the net growth rate per cycle. We show that tolerant mutants, characterized by a lower death rate, can significantly increase the bacterial fitness and potentially threaten the treatment efficacy, even if no change in resistance is involved. Based on the effective fitness model, we generalize the concept of trade-off induced fitness landscapes to the trade-off between growth and death rates, and study the evolution of tolerance as a random adaptive walk in this two-dimensional phenotype space.
