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
Department of Microbiology, University of Wisconsin-La Crosse, La Crosse, WI 54601, USA.
Emerging Technology Center for Pharmaceutical Development, University of Wisconsin-La Crosse, La Crosse, WI 54601, USA.
Antibiotics (Basel). 2017 Sep 11;6(3):17. doi: 10.3390/antibiotics6030017.
The mechanism of action for a new lead stilbene compound coded SK-03-92 with bactericidal activity against methicillin-resistant (MRSA) is unknown. To gain insight into the killing process, transcriptional profiling was performed on SK-03-92 treated vs. untreated . 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 and 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 and mutants compared to wild-type cells demonstrated that the 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 and other genes that could be tied to the SK-03-92 mechanism of action, biofilm formation, and drug persisters.
一种新型先导芪化合物SK-03-92对耐甲氧西林金黄色葡萄球菌（MRSA）具有杀菌活性，但其作用机制尚不清楚。为深入了解其杀菌过程，对经SK-03-92处理和未处理的菌株进行了转录谱分析。SK-03-92处理后，14个基因上调，38个基因下调。参与分选酶A产生、蛋白质代谢和转录调控的基因上调，而编码转运蛋白、嘌呤合成蛋白以及一个假定的双组分系统（SACOL2360（MW2284）和SACOL2361（MW2285））的基因则下调。定量实时聚合酶链反应分析证实了药物处理群体中相关基因的上调以及MW2284/MW2285和嘌呤生物合成基因的下调。与野生型细胞相比，对相关突变体进行定量实时聚合酶链反应分析表明，与野生型菌株相比，两个假定的双组分调节基因突变体均使相关基因上调。通过转录谱分析技术，我们确定了几种受SK-03-92处理调节的细胞途径，包括一个可能调节相关基因以及其他可能与SK-03-92作用机制、生物膜形成和药物持久性相关的基因的假定双组分系统。
