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

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. Fou...

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Autores principales: Schwan, William R., Polanowski, Rebecca, Dunman, Paul M., Medina-Bielski, Sara, Lane, Michelle, Rott, Marc, Lipker, Lauren, Wescott, Amy, Monte, Aaron, Cook, James M., Baumann, Douglas D., Tiruveedhula, V.V.N. Phani Babu, Witzigmann, Christopher M., Mikel, Cassandra, Rahman, Md Toufiqur
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617981/
https://www.ncbi.nlm.nih.gov/pubmed/28892020
http://dx.doi.org/10.3390/antibiotics6030017
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author Schwan, William R.
Polanowski, Rebecca
Dunman, Paul M.
Medina-Bielski, Sara
Lane, Michelle
Rott, Marc
Lipker, Lauren
Wescott, Amy
Monte, Aaron
Cook, James M.
Baumann, Douglas D.
Tiruveedhula, V.V.N. Phani Babu
Witzigmann, Christopher M.
Mikel, Cassandra
Rahman, Md Toufiqur
author_facet Schwan, William R.
Polanowski, Rebecca
Dunman, Paul M.
Medina-Bielski, Sara
Lane, Michelle
Rott, Marc
Lipker, Lauren
Wescott, Amy
Monte, Aaron
Cook, James M.
Baumann, Douglas D.
Tiruveedhula, V.V.N. Phani Babu
Witzigmann, Christopher M.
Mikel, Cassandra
Rahman, Md Toufiqur
author_sort Schwan, William R.
collection PubMed
description 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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spelling pubmed-56179812017-09-29 Identification of Staphylococcus aureus Cellular Pathways Affected by the Stilbenoid Lead Drug SK-03-92 Using a Microarray Schwan, William R. Polanowski, Rebecca Dunman, Paul M. Medina-Bielski, Sara Lane, Michelle Rott, Marc Lipker, Lauren Wescott, Amy Monte, Aaron Cook, James M. Baumann, Douglas D. Tiruveedhula, V.V.N. Phani Babu Witzigmann, Christopher M. Mikel, Cassandra Rahman, Md Toufiqur Antibiotics (Basel) Article 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. MDPI 2017-09-11 /pmc/articles/PMC5617981/ /pubmed/28892020 http://dx.doi.org/10.3390/antibiotics6030017 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Schwan, William R.
Polanowski, Rebecca
Dunman, Paul M.
Medina-Bielski, Sara
Lane, Michelle
Rott, Marc
Lipker, Lauren
Wescott, Amy
Monte, Aaron
Cook, James M.
Baumann, Douglas D.
Tiruveedhula, V.V.N. Phani Babu
Witzigmann, Christopher M.
Mikel, Cassandra
Rahman, Md Toufiqur
Identification of Staphylococcus aureus Cellular Pathways Affected by the Stilbenoid Lead Drug SK-03-92 Using a Microarray
title Identification of Staphylococcus aureus Cellular Pathways Affected by the Stilbenoid Lead Drug SK-03-92 Using a Microarray
title_full Identification of Staphylococcus aureus Cellular Pathways Affected by the Stilbenoid Lead Drug SK-03-92 Using a Microarray
title_fullStr Identification of Staphylococcus aureus Cellular Pathways Affected by the Stilbenoid Lead Drug SK-03-92 Using a Microarray
title_full_unstemmed Identification of Staphylococcus aureus Cellular Pathways Affected by the Stilbenoid Lead Drug SK-03-92 Using a Microarray
title_short Identification of Staphylococcus aureus Cellular Pathways Affected by the Stilbenoid Lead Drug SK-03-92 Using a Microarray
title_sort identification of staphylococcus aureus cellular pathways affected by the stilbenoid lead drug sk-03-92 using a microarray
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617981/
https://www.ncbi.nlm.nih.gov/pubmed/28892020
http://dx.doi.org/10.3390/antibiotics6030017
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