Heterogeneity in bacterial filamentation survival dynamics decrease in response to increased stress

The evolution of antibiotic resistance is a fundamental and lethal problem in disease management. Yet, while phenotypic diversity serves as the substrate for adaptation to emerge, including resistance, it is rarely quantified on a single cell level. Through the use of a novel dual reporter strain of E. coli we show that increased survival is correlated with continued DNA replication at both moderate and high levels of ciprofloxacin treatment but that the heterogeneity in response is increased at the lower treatment level. Similarly, we show that the survival time is also increased through a reduction in the abundance of misfolded proteins but that the mechanism of misfolded protein reduction is dependent on the treatment level. Taken as a whole, our results show the diverse range of survival tactics that are employed by cells in response to stress and highlight the power of single cell phenotyping in revealing potential evolutionary routes to resistance.