GSE184753
The novel peptide ScrA acts through the SaeRS two component system to regulate virulence gene expression in Staphylococcus aureus
Staphylococcus aureus is a Gram-positive opportunistic pathogen, which is carried by approximately 30 % of the population at any time. In addition to being a commensal S. aureus can cause an array of infections, ranging from mild skin and soft tissue infections to life threatening endocarditis and septicemia. S. aureus encodes a variety of virulence factors that facilitate its pathogenic lifestyle. Genes encoding these virulence factors are under tight control by a complex regulatory network, which includes, sigma factors, sRNAs, and protein-based systems, such as Two-Component Systems (TCS). Previous work in our lab demonstrated that overexpression of the sRNA tsr37 leads to an increase in cellular aggregation in the absence of host serum. We determined that the clumping phenotype was dependent on a previously unannotated 88 amino acid protein encoded within the tsr37 sRNA transcript (which we named ScrA for S. aureus clumping regulator A).  In addition to increased clumping, overexpression of ScrA also leads to increased biofilm formation. To investigate the mechanism of action of ScrA we performed mass spectrometry proteomics and RNA-sequencing in the ScrA overexpressing strain. A variety of virulence factors, including several surface adhesins were upregulated while several proteases were downregulated. Moreover, results showed a significant upregulation of the SaeRS two component system, suggesting that ScrA is influencing SaeRS activity. We go on to demonstrate that overexpression of ScrA in a saeR mutant abrogates the clumping/biofilm phenotypes confirming that ScrA functions via the Sae system. Finally, we identified the ArlRS TCS as a potential positive regulator of scrA expression. Collectively our results show that ScrA is an activator of the SaeRS system and suggests that ScrA may act as an intermediary between the ArlRS and SaeRS systems. Overall design: Six data sets in total.  Three biological replicates from wild type S. aureus cells containing the pMK4 empty vector, and three biological replicates from the wild type overproducing scrAB