Antibiotics (Sep 2017)

Identification of Staphylococcus aureus Cellular Pathways Affected by the Stilbenoid Lead Drug SK-03-92 Using a Microarray

  • William R. Schwan,
  • Rebecca Polanowski,
  • Paul M. Dunman,
  • Sara Medina-Bielski,
  • Michelle Lane,
  • Marc Rott,
  • Lauren Lipker,
  • Amy Wescott,
  • Aaron Monte,
  • James M. Cook,
  • Douglas D. Baumann,
  • V.V.N. Phani Babu Tiruveedhula,
  • Christopher M. Witzigmann,
  • Cassandra Mikel,
  • Md Toufiqur Rahman

DOI
https://doi.org/10.3390/antibiotics6030017
Journal volume & issue
Vol. 6, no. 3
p. 17

Abstract

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The mechanism of action for a new lead stilbene compound coded SK-03-92 with bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) is unknown. To gain insight into the killing process, transcriptional profiling was performed on SK-03-92 treated vs. untreated S. aureus. Fourteen genes were upregulated and 38 genes downregulated by SK-03-92 treatment. Genes involved in sortase A production, protein metabolism, and transcriptional regulation were upregulated, whereas genes encoding transporters, purine synthesis proteins, and a putative two-component system (SACOL2360 (MW2284) and SACOL2361 (MW2285)) were downregulated by SK-03-92 treatment. Quantitative real-time polymerase chain reaction analyses validated upregulation of srtA and tdk as well as downregulation of the MW2284/MW2285 and purine biosynthesis genes in the drug-treated population. A quantitative real-time polymerase chain reaction analysis of MW2284 and MW2285 mutants compared to wild-type cells demonstrated that the srtA gene was upregulated by both putative two-component regulatory gene mutants compared to the wild-type strain. Using a transcription profiling technique, we have identified several cellular pathways regulated by SK-03-92 treatment, including a putative two-component system that may regulate srtA and other genes that could be tied to the SK-03-92 mechanism of action, biofilm formation, and drug persisters.

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