Bistable Expression of Virulence Genes in Salmonella Leads to the Formation of an Antibiotic-Tolerant Subpopulation
Pooled results of three independent experiments analogous to the one shown in Figure 1, except that cells were exposed to a higher ciprofloxacin concentration, 10 µg/ml. We determined the ttss-1 expression levels of a total of 3,337 cells (measured as GFP fluorescence intensity at the last time point during antibiotic exposure) and recorded their fate during exposure to antibiotics. The histogram shows the number of cells in different GFP intensity categories, indicating ttss-1 expression levels. Background fluorescence intensity (measured in areas of the image not containing cells) was subtracted from the measured GFP values in order to allow pooling of different experiments. Color-coding denotes the probabilities to survive exposure to 10 µg/ml ciprofloxacin for each GFP intensity category. In three independent experiments, cells that express ttss-1 have a significantly higher survival probability (logistic regression with ANOVA, p = 0.03, 6.2×10−8, 4.2×10−3; N = 653, 1,208, and 1,476). In addition, columns were assigned visually to two categories according to their GFP expression (“GFP on,” “GFP off”), and the percentage of cells surviving in the different categories was calculated.