## 2 Results and Discussion
### General Transcriptome Response of SK-03-92 Treatment
\begin{table}
\begin{tabular}{l c l} \hline \hline
**Locus** & **Fold-Difference** & **Description** \\ \hline Stress Response & & \\ \hline SACOL1759 & \(-2.3\) & universal stress protein family \\ \hline Transporter & & \\ \hline SACOL0086 & \(-2.0\) & drug transporter, putative \\ SACOL0155 & \(-5.7\) & cation efflux family protein \\ SACOL0178 & \(-2.9\) & PTS system, IIBC components (\(scrBC\)) \\ SACOL0400 & \(-2.6\) & ascorbate-specific PTS system subunit IIC (\(ulaA\)) \\ SACOL0454 & \(-2.3\) & sodium:dicarboxylate symporter family protein \\ SACOL1018 & \(-2.3\) & sodium:alanine symporter family protein \\ SACOL1872 & \(-3.0\) & epidermin immunity protein F (\(epiE\)) \\ SACOL2146 & \(-2.7\) & PTS system, mannitol-specific IIBC components (\(mtIA\)) \\ SACOL2333 & \(-2.8\) & YnfiA family protein \\ SACOL2573 & \(-3.2\) & copper ion binding protein (\(copZ\)) \\ SACOL2664 & \(-2.3\) & mannose-6-phosphate isomerase (\(manA\)) \\ SACOL2718 & \(-4.6\) & 2-oxoglutate/malate translocator, sodium sulfate symporter \\ \hline Signaling/Regulation & & \\ \hline SACOL2360 & \(-14.1\) & LyfTR family regulator protein \\ SACOL2361 & \(-26.9\) & histidine kinase sensor membrane protein \\ SACOL2340 & \(2.2\) & transcriptional regulator TetR-family \\ \hline Cell Wall Associated & & \\ \hline SACOL0151 & \(-2.7\) & UDP-N-acetylglucosamine 2-epimerase Cap5P (\(cap5P\)) \\ SACOL0247 & \(-3.2\) & holin-like protein LrgA (\(lrgA\)) \\ SACOL0612 & \(-2.1\) & glycosyl transferase, group 1 family protein \\ SACOL1071 & \(-2.2\) & chitinase-related protein (\(iraE\)) \\ SACOL2554 & \(-2.0\) & holin-like protein CidB (\(cidB\)) \\ SACOL2539 & \(4.2\) & sortase A (\(strA\)) \\ \hline Anabolism/Nucleic Acids & & \\ \hline SACOL013 & \(-2.1\) & \(5^{\prime}\) nucleotide family protein \\ SACOL1078 & \(-3.2\) & phosphoribosylformylglycinaidine synthase II (\(purL\)) \\ SACOL1082 & \(-2.5\) & bifunctional purine biosynthesis protein (\(purH\)) \\ SACOL1083 & \(-2.6\) & phosphoribosylamine-glycine ligase (\(purD\)) \\ SACOL2329 & \(-3.5\) & ribose 5-phosphate isomerase (\(priA\)) \\ SACOL2111 & \(2.2\) & thymidine kinase (\(dtk\)) \\ SACOL2377 & \(2.3\) & conserved hypothetical protein \\ \hline Anabolism/Proteostasis & & \\ \hline SACOL0085 & \(-2.5\) & peptidase, M20.M25/M40 family \\ SACOL2605 & \(-9.6\) & ribulosamine 3-kinase \\ SACOL0457 & \(2.6\) & conserved hypothetical protein, heat induced stress \\ SACOL0590 & \(2.4\) & 305 ribosomal protein L7 Ae \\ SACOL0877 & \(2.5\) & glycine cleavage system H protein (\(gcvH\)) \\ SACOL1907 & \(2.4\) & ribosomal large subunit pseudouridine synthase (\(tluD\)) \\ SACOL1939 & \(2.3\) & phosphotyrosine protein phosphatase (\(ptpA\)) \\ SACOL2596 & \(2.6\) & metallo-dependent amidohydrolase \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Microarray analysis of genes dysregulated in _S. aureus_ MW2 cells treated with 8\(\times\) the SK-03-92 MIC vs. untreated cells. Three genes associated with purine synthesis were downregulated: _purD_, _purH_, and _purL_. Purine metabolism is a necessary part of DNA synthesis and energy production in _S. aureus_[50]. Genes involved in purine metabolism are often downregulated after treatment with a drug or plant extract [51; 52; 53]. In addition, one gene associated with pyrimidine synthesis, _tdk_, was upregulated. Thymidine kinase transfers the terminal phosphate from ATP to thymidine or deoxyuridine [54]. A decrease in the synthesis of purines coupled with an increase in phosphorylation of pyrimidines could result in a dramatic reorganization of the intracellular nucleotide pool. Moreover, less purine metabolism is often tied to drug persister populations [55; 56]. Disruption of nucleotide metabolism in a library of _S. aureus_ transposon insertion mutants caused a decrease in persister formation frequency when treated with rifampicin [57]. Consistent with the formation of persister strains, mRNA levels of genes linked to programmed cell death (PCD) were decreased in _S. aureus_ cultures treated with SK-03-92.