Supplementary Materials

Supplementary Material for:

TarO-specific inhibitors of wall teichoic acid biosynthesis restore β-lactam efficacy against methicillin-resistant staphylococci

Sang Ho Lee, Hao Wang, Marc Labroli, Sandra Koseoglu, Paul Zuck, Todd Mayhood, Charles Gill, Paul Mann, Xinwei Sher, Sookhee Ha, Shu-Wei Yang, Mihir Mandal, Christine Yang, Lianzhu Liang, Zheng Tan, Paul Tawa, Yan Hou, Reshma Kuvelkar, Kristine DeVito, Xiujuan Wen, Jing Xiao, Michelle Batchlett, Carl J. Balibar, Jenny Liu, Jianying Xiao, Nicholas Murgolo, Charles G. Garlisi, Payal R. Sheth, Amy Flattery, Jing Su,* Christopher Tan,* Terry Roemer*

*Corresponding author. E-mail: jing.su2{at}merck.com (J.S.); christopher_tan{at}merck.com (C.T.); terry_roemer{at}merck.com (T.R.)

Published 9 March 2016, Sci. Transl. Med. 8, 329ra32 (2016)
DOI: 10.1126/scitranslmed.aad73648

This PDF file includes:

  • Materials and Methods
  • Fig. S1. Validation of wall teichoic acid–targeted phenotypic screen strategy.
  • Fig. S2. Microbiological and biochemical activity of tarocin A derivatives.
  • Fig. S3. Comparative protein alignment of TarO and MraY TM domains.
  • Fig. S4. Alignment of TarO homologs.
  • Fig. S5. Surface modeling of TarO intracellular binding pocket.
  • Fig. S6. Bactericidal effect of β-lactam and tarocin combination.
  • Fig. S7. FOR of tarocin A2 in combination with imipenem or dicloxacillin.
  • Fig. S8. Comparative analysis of tarocin, tunicamycin, and ticlopidine.
  • Fig. S9. Structure verification of ticlopidine by LC-MS and nuclear magnetic resonance.
  • Fig. S10. Comparative analysis of clinical MRSA coverage versus TarO biochemical activities.
  • Table S1. Antibiogram of clinical MRSA isolates.
  • Table S2. Dicloxacillin and tarocin A2 synergy profile of MRSA and MRSE clinical isolates.
  • Table S3. Pharmacokinetic analysis of dicloxacillin by subcutaneous administration.

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