Supplementary Materials

Supplementary Material for:

Metformin as adjunct antituberculosis therapy

Amit Singhal,* Liu Jie, Pavanish Kumar, Gan Suay Hong, Melvin Khee-Shing Leow, Bhairav Paleja, Liana Tsenova, Natalia Kurepina, Jinmiao Chen, Francesca Zolezzi, Barry Kreiswirth, Michael Poidinger, Cynthia Chee, Gilla Kaplan, Yee Tang Wang, Gennaro De Libero*

*Corresponding author. E-mail: amit_singhal{at}immunol.a-star.edu.sg(A.S.); gennaro_delibero{at}immunol.a-star.edu.sg (G.D.L.)

Published 19 November 2014, Sci. Transl. Med. 6, 263ra159 (2014)
DOI: 10.1126/scitranslmed.3009885

This PDF file includes:

  • Fig. S1. Inhibition of the intracellular growth of mycobacteria by FDA-approved compounds.
  • Fig. S2. MET inhibits the intracellular growth of mycobacteria in an AMPK-dependent manner.
  • Fig. S3. MET does not have direct effect on Mtb.
  • Fig. S4. MET induces mROS but not cROS in the early phase of infection.
  • Fig. S5. Scavenging ROS inhibits MET-mediated mROS production and antimycobacterial effects.
  • Fig. S6. Autophagy is not required for MET-mediated inhibition of mycobacterial growth.
  • Fig. S7. MET does not induces neither cell death and cytochrome c release in mycobacterium-infected cells.
  • Fig. S8. MET enhances INH and ETH efficacy in a mouse model of infection.
  • Fig. S9. Effect of MET on infiltration of CD4+ and CD8+ T cells in the lungs of Mtb-infected mice.
  • Fig. S10. MET enhances CD8+ T cell responses in uninfected mice.
  • Fig. S11. MET modulates the genes associated with inflammatory responses during mycobacterial infection.
  • Table S1. List of FDA-approved compounds used, indicating the class they belong, their action, clinical indication they are prescribed for and their effect on intracellular M. bovis BCG survival.
  • Table S2. MET induces phagosome-lysosome fusion in M. bovis BCG-infected hMDM and THP-1 cells.
  • Table S3. Proportion of mice with no detectable CFUs during INH therapy with and without MET after 4 weeks of treatment (that is, day 35 after infection) in two different experiments.
  • Table S4. Differentially expressed genes between lung cells of untreated Mtb-infected mice versus uninfected mice.
  • Table S5. Differentially expressed genes between lung cells of MET-treated versus untreated Mtb-infected mice.
  • Table S6. Enrichment of significant canonical pathways (IPA analysis) in differentially expressed genes between lung cells of untreated Mtb-infected mice versus uninfected mice.
  • Table S7. Enrichment of significant canonical pathways (IPA analysis) in differentially expressed genes between lung cells of MET-treated Mtb-infected mice versus untreated Mtb-infected mice.
  • Table S8. Clinical characteristics of patients with comorbidity of TB and DM.
  • Table S9. Clinical characteristics of 220 diabetic (DM) patients.
  • Table S10. Characteristics of MDR strains of Mtb used in the study.
  • Table S11. P values for Fig. 1.
  • Table S12. P values for Fig. 2.
  • References (50, 51)

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