Supplementary Materials

Supplementary Material for:

Targeting protein biotinylation enhances tuberculosis chemotherapy

Divya Tiwari, Sae Woong Park, Maram M. Essawy, Surendra Dawadi, Alan Mason, Madhumitha Nandakumar, Matthew Zimmerman, Marizel Mina, Hsin Pin Ho, Curtis A. Engelhart, Thomas Ioerger, James C. Sacchettini, Kyu Rhee, Sabine Ehrt, Courtney C. Aldrich, Véronique Dartois,* Dirk Schnappinger*

*Corresponding author. Email: dis2003{at}med.cornell.edu (D.S.); dartoiva{at}njms.rutgers.edu (V.D.)

Published 25 April 2018, Sci. Transl. Med. 10, eaal1803 (2018)
DOI: 10.1126/scitranslmed.aal1803

This PDF file includes:

  • Materials and Methods
  • Fig. S1. Bio-AMS kills Mtb in medium with different carbon sources and is not acutely toxic to mouse macrophages.
  • Fig. S2. Evaluation of mitochondrial toxicity.
  • Fig. S3. Emergence of Mtb mutants resistant to Bio-AMS.
  • Fig. S4. Quantification of Mtb-associated Bio-AMS and biotin sulfonamide.
  • Fig. S5. PK profiles and metabolism of Bio-AMS in mice.
  • Fig. S6. Putative Bio-AMS metabolic and degradation pathways.
  • Fig. S7. Construction of the Mtb BPL-DUC strain.
  • Fig. S8. Impact of atc on BPL expression and protein biotinylation.
  • Fig. S9. Histopathology of lungs infected with the Mtb BPL-DUC strain.
  • Fig. S10. Bio-AMS treatment inhibits protein biotinylation and results in loss of Mtb acid-fastness.
  • Fig. S11. Growth of Mtb ΔbioA in low concentrations of biotin increases potency of rifampicin but not ethambutol.
  • Table S1. Whole-genome sequencing of Bio-AMS–resistant Mtb strains.
  • Table S2. Genes whose transcripts changed more than threefold in three Bio-AMS–resistant strains.
  • Table S3. Kinetic parameters of Mtb Rv3406.
  • Table S4. PK parameters of Bio-AMS after intravenous, intraperitoneal, and oral administration.
  • Table S5. Tolerability of Bio-AMS at ascending intraperitoneal doses in CD-1 mice.
  • Table S6. Concentrations of rifampicin and doxycycline in the plasma of CD-1 mice receiving rifampicin alone or rifampicin with doxycycline in the diet after a single dose (10 mg/kg) of rifampicin and at a steady state.
  • Table S7. Distribution of doxycycline in Mtb-infected rabbit lung lesions relative to plasma after administration of doxycycline in chow for 7 days.
  • Table S8. Strains and plasmids.

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