Fig. 3: M. tuberculosis single-cell analysis of PurF inhibition.
From: Targeting de novo purine biosynthesis for tuberculosis treatment
a, M. tuberculosis expressing TdTomato, cultured in a microfluidic device and imaged over 312 h at 1-h intervals, exposed to 0.6 µM JNJ-6640 (95–238 h). NB mix, nucleobase mix (239–311 h). Snapshot images of representative microcolony are shown in magenta (TdTomato fluorescence). Scale bars, 3 µm. b, Fraction of intact cells upon exposure to 0.6 µM JNJ-6640 (grey shading) and after washout and supplementation with 1× NB mix (blue shading), from the single-cell imaging experiments. The lines represent independent xy frames imaged. n = 1,195 cells, across 15 fields. A representative dataset from three independent experiments. c, Representative snapshots of M. tuberculosis replisome reporter strain (MTB::gfp-dnaN, green channel) expressing cytoplasmic TdTomato (magenta channel), before, during and after exposure to 0.6 µM JNJ-6640. Bacteria undergoing DNA replication identified by green foci representing active replisome complex. Scale bars, 3 µm. d, Number of bacteria with a GFP–DnaN foci when exposed to 0.6 µM JNJ-6640 (grey shading) and after washout and supplementation with 1× NB mix (blue shading). The lines (n = 8) represent individual xy positions imaged over time. A representative dataset from two independent experiments.
