Beyond resistance and tolerance: rethinking evolutionary responses to antibiotics from the perspective of individual bacterial cells

Antibiotic resistance and tolerance are thought to be the key phenotypic traits that underpin evolutionary adaptation to antibiotics. However, the concepts of resistance and tolerance can be traced back to population-level assays developed by Fleming in the 1920s. Recent single-cell studies have shown that population responses to antibiotics are driven by a dynamic interplay between cell birth and death, challenging the concepts of resistance and tolerance at the level of individual cells. In this Perspective, we show that ecological models of population growth provide a tool to connect the population-level responses to antibiotics measured by classic assays (ie growth rate) with individual cellular phenotypes (ie birth and death rates). In this model, resistance and tolerance represent emergent properties of bacterial populations that change as an indirect consequence of selection on cell birth and death rates. We argue that this model challenges established concepts and highlights the need to better understand evolutionary responses to antibiotics from the perspective of cellular phenotypes.