A single-cell view of multiple antibiotic resistance in Escherichia coli

From Q-bio

The chromosomal mar operon is responsible for the multiple antibiotic resistance phenotype in Escherichia coli. This operon is composed of a repressor, marR, and an activator, marA. MarA governs the expression of the efflux pump AcrAB-TolC, which is the main determinant of multi drug resistance. The genetics of multiple antibiotic resistance has been studied solely at the population level. Single cell studies of the dynamics of the mar operon are necessary in order to understand cellular variability of resistance to antibiotics. Using the fluorescent protein Venus-YFP, we monitor in real time the activity of the mar promoter in single cells across micro-colonies. This approach enables us to construct genealogies of promoter activities across several generations. We determine the activity of the mar promoter for different values of the inducer salicylate. We find that in response to a steady level of inducer, mar promoter activity is widely heterogeneous across genetically identical daughter cells. Often different promoter activity levels are maintained and inherited for several generations. We find that heterogeneity in promoter activity varies with inducer level. The mar promoter activity is homogeneous throughout colonies in a ΔmarR mutant strain.