# Global Transcriptomic Response of _Staphylococcus aureus_ to Viulent Bacteriophage Infection
## 4 Discussion  
The current work, along with our previous study, describes changes in the gene expression profiles during _S. aureus_ SA515 infection with the vB_SauM-515A1 bacteriophage. Previously, we established the transcriptional landscape of the vB_SauM-515A1 bacteriophage and demonstrated that most of the genes are constitutively expressed throughout the infection. Only by the 30 th minute of infection was late gene transcription observed, without evident shutdown of the early genes [25]. Here we showed that only 10% of _S. aureus_ genes altered their expression, which is consistent with previously published reports on various phage-infected bacteria, e.g., 7.1% of host genes were differentially expressed in PaP1-infected (_Myoviridae_) _Pseudomonas aeruginosa_[18], 2.7% in o29-infected \begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Region** & **Contigs** & \multicolumn{2}{c}{**Possible Phage Match and Its Characteristics**} \\ \hline  & & **Phase** & **Phase Size, bp** & **Phage CDSs** \\ \hline
1 &
\begin{tabular}{c} Saur515\_contig\_7 \\ Saur515\_contig\_22 \\ \end{tabular} & _Staphylococcus phage_ phiJB (NC\_028669) & 43,012 & 70 \\ \hline
2 &
\begin{tabular}{c} Saur515\_contig\_5 \\ Saur515\_contig\_21 \\ Saur515\_contig\_28 \\ \end{tabular} & _Staphylococcus phage_ phi2958 PVL (NC\_011344.1) & 47,342 & 59 \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Prediction of prophage regions in the _S. aureus_ strain SA515 genome using PHASTER. \begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Virulence Factor** & **Gene** & \multicolumn{3}{c}{**Fold Change \({}^{*}\)**} \\  & & **5 min** & **15 min** & **30 min** \\ \hline \multicolumn{5}{c}{**Downregulated genes**} \\ \hline toxin superantigen-like protein, exotoxin 14 & _set14_ & \(\mathbf{-2.09}\) & \(1.10\) & \(-1.36\) \\ staphylocoagulase & _caa_ & \(\mathbf{-2.31}\) & \(-1.00\) & \(1.34\) \\ triacylglycerolglycerol lipase & _lip_ & \(\mathbf{-2.20}\) & \(-1.19\) & \(-1.09\) \\ \hline \multicolumn{5}{c}{**UPEgulated genes**} \\ \hline gamma-hemolysin component C precursor, HlgB & _hlgB_ & \(-1.53\) & \(\mathbf{2.53}\) & \(\mathbf{4.31}\) \\ gamma-hemolysin component C precursor, HlgC & _hllgC_ & \(-1.36\) & \(\mathbf{2.98}\) & \(\mathbf{4.00}\) \\ superantigen-like protein, exotoxin set40 & _set15_ & \(-1.27\) & \(1.28\) & \(\mathbf{2.85}\) \\ fibrinogen-binding protein & _efb_ & \(-1.26\) & \(1.66\) & \(\mathbf{2.99}\) \\ ESAT-6/WXG100 family secreted protein EsxA/YukE & _esxA_ & \(1.14\) & \(\mathbf{3.04}\) & \(\mathbf{4.99}\) \\ protein secretion system Essa & _esxA_ & \(1.00\) & \(1.29\) & \(\mathbf{2.04}\) \\ immunoglobulin G-binding protein SBI & _sbi_ & \(-1.14\) & \(1.46\) & \(\mathbf{2.62}\) \\ staphylococcal complement inhibitor SCIN & _scn_ & \(-1.00\) & \(1.68\) & \(\mathbf{3.11}\) \\ \hline \hline \end{tabular} \({}^{*}\) Values in bold meet the corresponding selection criteria (FC \(\geq\) 12; FDR \(<\) 0.001).  
\end{table} 
Table 2: Expression of SA515 genes related to virulence after phage infection. (_Podoviridae_) _Bacillus subtilis_[19], and 15.6% in \(\varphi\)Abp1-infected (_Autographviridae_) _Acineobacter bumanii_[20]. Notably, the strongest response of _S. aureus_ was registered at the onset of infection (5 min post-infection), when a relatively equal number of genes were up- and downregulated. Intriguingly, most of the phage genes were also expressed at 5 min post-infection; this may suggest a phage-controlled regulation of bacterial gene expression. During the onset of infection, the nucleic acid metabolism underwent the most significant changes, which is typical for various phage-infected bacterial species [42]. The purine biosynthesis pathway is crucial for cell growth and is involved in bacterial survival and virulence [43]. Moreover, purine synthesis is associated with (p)ppGpp alarmone level [44]. The accumulation of (p)ppGpp can lead to the inhibition of transcription, translation, and premature cell death [45; 46], following which the bacteriophage does not multiply effectively within the cell.