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Antibiotics 2017, 6(3), 17; https://doi.org/10.3390/antibiotics6030017

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

1
Department of Microbiology, University of Wisconsin-La Crosse, La Crosse, WI 54601, USA
2
Emerging Technology Center for Pharmaceutical Development, University of Wisconsin-La Crosse, La Crosse, WI 54601, USA
3
School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA
4
Department of Chemistry and Biochemistry, University of Wisconsin-La Crosse, La Crosse, WI 54601, USA
5
Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, USA
6
Department of Mathematics and Statistics, University of Wisconsin-La Crosse, La Crosse, WI 54601, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Christopher C. Butler
Received: 28 July 2017 / Revised: 25 August 2017 / Accepted: 7 September 2017 / Published: 11 September 2017
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Abstract

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. View Full-Text
Keywords: stilbene; microarray; Staphylococcus aureus; gene regulation; drug mechanism of action; sortase; biofilm stilbene; microarray; Staphylococcus aureus; gene regulation; drug mechanism of action; sortase; biofilm
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Schwan, W.R.; Polanowski, R.; Dunman, P.M.; Medina-Bielski, S.; Lane, M.; Rott, M.; Lipker, L.; Wescott, A.; Monte, A.; Cook, J.M.; Baumann, D.D.; Tiruveedhula, V.P.B.; Witzigmann, C.M.; Mikel, C.; Rahman, M.T. Identification of Staphylococcus aureus Cellular Pathways Affected by the Stilbenoid Lead Drug SK-03-92 Using a Microarray. Antibiotics 2017, 6, 17.

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