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
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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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