Fig. 2: Subcellular localization of intracellular M. tuberculosis governs its bioenergetic state, replication rate, and response to drugs.

a A representative image of THP-1 macrophages infected with Mtb-overexpressing PHR-mCherry. The inset shows the ratiometric view of perinuclear and peripheral bacilli. b Plot of ATP/ADP ratio of mycobacteria infecting THP-1 macrophages at different distances from the nucleus (n = 60) (One-tailed, Mann–Whitney U test, CI-95%). c THP-1 macrophages were infected with MtbH37Rv (SSB-GFP, smyc’:: mCherry). The figure shows the representative image of THP-1 macrophages infected with Mtb-overexpressing SSB-GFP. d Percent MtbH37Rv expressing SSB-GFP (n = 60) foci located at different distances from the nucleus was quantified from experiments described in (c) (One-tailed, unpaired Student’s t test, CI-95%). e THP-1 macrophages were infected with GFP-MtbH37Rv for 3 h and treated with Rifampicin or Isoniazid for 48 h post-infection. The figure shows the representative image of GFP-MtbH37Rv in untreated, Rifampicin-treated, and Isoniazid-treated macrophages. f Percent population of GFP-MtbH37Rv survived at different distances from the nucleus upon antibiotic treatments (n > 200) was quantified from experiments described in (e) (One-tailed, unpaired Student’s t test, CI-95%). Data in b, d, f represent mean ± SEM from three independent biological experiments. Scale Bar: 10 μm.