Fig. 1: K. pneumoniae population dynamics during bacteremic pneumonia.
From: Patterns of Klebsiella pneumoniae bacteremic dissemination from the lung
Mice were infected with KPPR1-STAMPR, a wild-type K. pneumoniae barcoded library in a model of pneumonia that progresses to bacteremia. Tissues were harvested 24- or 48-hours post-infection (black circles or blue squares, respectively) and analyzed with quantitative culture and the STAMPR pipeline. A The bacterial burden in each tissue at the time of harvest is displayed as log10 CFU/site. The dotted line indicates the infection inoculum, 1 x 106 CFU/mouse. B The founding population size in each tissue was estimated by the STAMPR pipeline and displayed as log10 Ns. The dotted line indicates the resolution limit of the library, ~8 × 105 founders, the maximum complexity for any site. C The extent of clonal replication is estimated by log10(CFU/Ns). D The extent of replication evenness is displayed as log10(Ns/Nb). The dotted line indicates a theoretical value 0, representing even replication. E The genetic distance (GD) between the lung and secondary organs, or (F) the spleen and other secondary organs was modeled by the STAMPR pipeline at 24- or 48-hours. In all, data is represented as a box plot with points representing individual animals, whisker end points indicating the minimum and maximum observed values, box boundaries representing the 25th and 75th percentile, and the middle line representing the median value. In (A–F), differences between tissues at 24- or 48- hours were assessed with two-tailed unpaired t-tests and corrected for multiple comparisons; p-values are displayed above each comparison. In (A–F), comparisons between the lung and secondary organs (A–E) or the spleen and other organs F within each timepoint was assessed by ordinary one-way ANOVA and corrected for multiple comparisons: #p < 0.05, ##p < 0.01, ###p < 0.001, ####p < 0.0001 for the 24- hour group and +p < 0.05, ++p < 0.01, +++p < 0.001, ++++p < 0.0001 for the 48-hour group. Specifically, in (A) the p-value between the lung and spleen, liver, or blood at 24-hours is <0.0001, <0.0001, and 0.0003; the p-value between the lung and spleen, liver, or blood at 48-hours is 0.0002, 0.0022, and 0.6254, respectively. In (B) the p-value between the lung and spleen, liver, or blood at 24-hours is <0.0001 for each comparison; the p-value between the lung and spleen, liver, or blood at 48-hours is <0.0001, 0.0012, and <0.0001, respectively. In (C) the p-value between the lung and spleen, liver, or blood at 24-hours is 0.2747, 0.0738, and 0.9801; the p-value between the lung and spleen, liver, or blood at 48-hours is 0.4235, 0.5367, and 0.2186, respectively. In (D) the p-value between the lung and spleen, liver, or blood at 24-hours is 0.0004, 0.0172, and 0.0012; the p-value between the lung and spleen, liver, or blood at 48-hours is 0.0384, 0.1405, and 0.0042, respectively. In (E) the p-value between the spleen and liver is 0.9775 and between the spleen and blood is 0.9994 at 24-hours; the p-value between the spleen and liver is 0.9932 and between the spleen and blood is 0.6551 at 48-hours. In (F) the p-value between the lung and liver or the lung and blood is <0.0001 for both comparisons at 24-hours; the p-value between the lung and liver is 0.0223 and between the liver and blood is 0.9897 at 48-hours. For the 24-hour group, n = 17 mice in 5 independent trials. For the 48-hour group, n = 9 mice in a single trial. STAMPR analysis was excluded for animals with no detectable tissue CFU or any sample with low sequencing quality. Source data are provided within the Source Data file.
