Fig. 2
Fitness cost kinetics of DCSR mutants. a Relative fitness of DCSR mutants calculated using competition assays in vitro. DCSR mutants are grouped according to their mutations and the relative fitness is followed over time. Parent strain relative fitness W = 1. The data are representative of three independent experiments. The data points are representative of the mean, whereas error bars represent standard error SEM, n = 2. b Relative fitness of DCSR mutants obtained during macrophage infection. DCSR mutants are grouped according to their mutations. Experiments were carried out with human blood-derived monocytes differentiated into macrophages. Bacterial uptake and survival inside naive or interferon-gamma-activated macrophages is compared over time with the wild-type strain (black dots and line). The data shown are from one experiment representative of three independent experiments, where each macrophage culture originated from at least three blood donors and were pooled prior to infection to minimize donor variability. The data points are representative of the mean whereas error bars represent standard error SEM, n = 3. c Assessment of fitness cost associated with DCS resistance in the mouse model of infection. DCSR mutants (1, 4, 5, 6, 9, and 11) and parent strain were used in a low-dose aerosol infection murine model (using C57BL/6 mice). The CFUs obtained from mouse lungs are shown for days 0, 30, 70 and 120 post infection. The data for DCSR4 are representative of two independent experiments, whereas for DCSR mutants (1, 5, 6, 9, and 11) are from a single infection experiment. Five mice were infected per strain per timepoint. The data points are representative of the mean, whereas error bars represent standard error SEM, n = 5. d The relative fitness calculated for representative DCSR mutants (1, 4, 5, 6, 9, and 11) at the endpoint in vitro (day 56) competition assays, macrophages infection assays (day 3), and in vivo experiments (day 120), compared with the parent strain. Source data are provided as a Source Data file
