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...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2017-09-01
|
| Series: | Antibiotics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-6382/6/3/17 |
| _version_ | 1818084277239152640 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | William R. Schwan |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-10T19:51:20Z |
| format | Article |
| id | doaj.art-2b79c41766a14937a9b1eef60589aabb |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-12-10T19:51:20Z |
| publishDate | 2017-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-2b79c41766a14937a9b1eef60589aabb2022-12-22T01:35:45ZengMDPI AGAntibiotics2079-63822017-09-01631710.3390/antibiotics6030017antibiotics6030017Identification of Staphylococcus aureus Cellular Pathways Affected by the Stilbenoid Lead Drug SK-03-92 Using a MicroarrayWilliam R. Schwan0Rebecca Polanowski1Paul M. Dunman2Sara Medina-Bielski3Michelle Lane4Marc Rott5Lauren Lipker6Amy Wescott7Aaron Monte8James M. Cook9Douglas D. Baumann10V.V.N. Phani Babu Tiruveedhula11Christopher M. Witzigmann12Cassandra Mikel13Md Toufiqur Rahman14Department of Microbiology, University of Wisconsin-La Crosse, La Crosse, WI 54601, USADepartment of Microbiology, University of Wisconsin-La Crosse, La Crosse, WI 54601, USASchool of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USADepartment of Microbiology, University of Wisconsin-La Crosse, La Crosse, WI 54601, USADepartment of Microbiology, University of Wisconsin-La Crosse, La Crosse, WI 54601, USADepartment of Microbiology, University of Wisconsin-La Crosse, La Crosse, WI 54601, USADepartment of Microbiology, University of Wisconsin-La Crosse, La Crosse, WI 54601, USADepartment of Microbiology, University of Wisconsin-La Crosse, La Crosse, WI 54601, USAEmerging Technology Center for Pharmaceutical Development, University of Wisconsin-La Crosse, La Crosse, WI 54601, USADepartment of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, USADepartment of Mathematics and Statistics, University of Wisconsin-La Crosse, La Crosse, WI 54601, USADepartment of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, USADepartment of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, USADepartment of Microbiology, University of Wisconsin-La Crosse, La Crosse, WI 54601, USADepartment of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, USAThe 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.https://www.mdpi.com/2079-6382/6/3/17stilbenemicroarrayStaphylococcus aureusgene regulationdrug mechanism of actionsortasebiofilm |
| spellingShingle | 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 Identification of Staphylococcus aureus Cellular Pathways Affected by the Stilbenoid Lead Drug SK-03-92 Using a Microarray Antibiotics stilbene microarray Staphylococcus aureus gene regulation drug mechanism of action sortase biofilm |
| 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 | stilbene microarray Staphylococcus aureus gene regulation drug mechanism of action sortase biofilm |
| url | https://www.mdpi.com/2079-6382/6/3/17 |
| work_keys_str_mv | AT williamrschwan identificationofstaphylococcusaureuscellularpathwaysaffectedbythestilbenoidleaddrugsk0392usingamicroarray AT rebeccapolanowski identificationofstaphylococcusaureuscellularpathwaysaffectedbythestilbenoidleaddrugsk0392usingamicroarray AT paulmdunman identificationofstaphylococcusaureuscellularpathwaysaffectedbythestilbenoidleaddrugsk0392usingamicroarray AT saramedinabielski identificationofstaphylococcusaureuscellularpathwaysaffectedbythestilbenoidleaddrugsk0392usingamicroarray AT michellelane identificationofstaphylococcusaureuscellularpathwaysaffectedbythestilbenoidleaddrugsk0392usingamicroarray AT marcrott identificationofstaphylococcusaureuscellularpathwaysaffectedbythestilbenoidleaddrugsk0392usingamicroarray AT laurenlipker identificationofstaphylococcusaureuscellularpathwaysaffectedbythestilbenoidleaddrugsk0392usingamicroarray AT amywescott identificationofstaphylococcusaureuscellularpathwaysaffectedbythestilbenoidleaddrugsk0392usingamicroarray AT aaronmonte identificationofstaphylococcusaureuscellularpathwaysaffectedbythestilbenoidleaddrugsk0392usingamicroarray AT jamesmcook identificationofstaphylococcusaureuscellularpathwaysaffectedbythestilbenoidleaddrugsk0392usingamicroarray AT douglasdbaumann identificationofstaphylococcusaureuscellularpathwaysaffectedbythestilbenoidleaddrugsk0392usingamicroarray AT vvnphanibabutiruveedhula identificationofstaphylococcusaureuscellularpathwaysaffectedbythestilbenoidleaddrugsk0392usingamicroarray AT christophermwitzigmann identificationofstaphylococcusaureuscellularpathwaysaffectedbythestilbenoidleaddrugsk0392usingamicroarray AT cassandramikel identificationofstaphylococcusaureuscellularpathwaysaffectedbythestilbenoidleaddrugsk0392usingamicroarray AT mdtoufiqurrahman identificationofstaphylococcusaureuscellularpathwaysaffectedbythestilbenoidleaddrugsk0392usingamicroarray |