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Bistable Expression of Virulence Genes in Salmonella Leads to the Formation of an Antibiotic-Tolerant Subpopulation

Figure 3

Selection for genetically avirulent mutants is reversed when exposed to antibiotic.

Dynamics of the fraction of ΔhilD cells in mixed cultures with wild-type cells over time. Cultures were inoculated with approximately 1∶1 ratios of the two strains. A kanamycin resistance marker was used to distinguish between strains. Without antibiotic challenge, ΔhilD cells increase in frequency relative to wild-type cells (blue boxes), whereas exposure to 0.05 µg/ml ciprofloxacin reverses the trend, and ΔhilD cells decrease in frequency relative to wild type (red boxes). Boxes span the range between upper and lower quartile; thick lines denote the median; whiskers denote the highest and lowest values still within 1.5 interquartile ranges of the upper and lower quartiles, respectively; empty circles represent data points that are outside this range. The addition of ciprofloxacin has a significant influence on the outcome of competition (two way ANOVA, Time×Treatment interaction, p<2×10−16, N = 20).

Figure 3