Supplementary Materials

The PDF file includes:

  • Materials and Methods
  • Fig. S1. Phenotypic drug tolerance in Mtb during infection.
  • Fig. S2. Flow cytometry–based quantification of redox heterogeneity in Mtb using Mrx1-roGFP2.
  • Fig. S3. EMSH-reduced population is tolerant to Inh.
  • Fig. S4. Transcriptome of Mtb from EMSH-reduced and EMSH-basal fractions.
  • Fig. S5. Measuring phagosomal pH of THP-1 macrophages infected with Mtb/Mrx1-roGFP2.
  • Fig. S6. The transcriptome of Mtb from the EMSH-reduced fraction overlaps with low pH–specific WhiB3 regulon.
  • Fig. S7. WT Mtb generates H2S gas in a pH-dependent manner.
  • Fig. S8. Generation and characterization of MtbmetB and MtbsufR.
  • Fig. S9. Deletion of metB and sufR does not impair growth and metabolism of Mtb.
  • Fig. S10. Phagosomal acidification is required for the redox-dependent multidrug tolerance of Mtb.
  • Fig. S11. Drug-tolerant EMSH-reduced population is replicative and has high efflux pump activity.
  • Fig. S12. CQ counteracts drug tolerance in vivo to reduce lung tissue damage in chronic model of Mtb infection.
  • Fig. S13. Long-term CQ treatment of chronically infected BALB/c mice deacidifies macrophage pH without affecting oxidative stress and necrosis.
  • Fig. S14. Model depicting various mechanisms underlying redox-mediated drug tolerance in replicating Mtb.
  • References (94112)

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Other Supplementary Material for this manuscript includes the following:

  • Table S1 (Microsoft Excel format). List of differentially expressed genes from DESeq2 for EMSH-reduced, EMSH-basal, and in vitro control samples.
  • Table S2 (Microsoft Excel format). List of differentially expressed genes from DESeq2 for WT Mtb, MtbwhiB3, and whiB3-Comp strains at pH 6.6 and pH 4.5 used to specify the low pH–inducible WhiB3 regulon.
  • Table S3 (Microsoft Excel format). List of EMSH-reduced and EMSH-basal differentially expressed genes used to generate custom heat maps.
  • Table S4 (Microsoft Excel format). List of strains and primers used in this study.