Impacts of the Type I Toxin–Antitoxin System, SprG1/SprF1, on Staphylococcus aureus Gene Expression

Abstract

Type I toxin–antitoxin (TA) systems are widespread genetic modules in bacterial genomes. They express toxic peptides whose overexpression leads to growth arrest or cell death, whereas antitoxins regulate the expression of toxins, acting as labile antisense RNAs. The Staphylococcus aureus (S. aureus) genome contains and expresses several functional type I TA systems, but their biological functions remain unclear. Here, we addressed and challenged experimentally, by proteomics, if the type I TA system, the SprG1/SprF1 pair, influences the overall gene expression in S. aureus. Deleted and complemented S. aureus strains were analyzed for their proteomes, both intracellular and extracellular, during growth. Comparison of intracellular proteomes among the strains points to the SprF1 antitoxin as moderately downregulating protein expression. In the strain naturally expressing the SprG1 toxin, cytoplasmic proteins are excreted into the medium, but this is not due to unspecific cell leakages. Such a toxin-driven release of the cytoplasmic proteins may modulate the host inflammatory response that, in turn, could amplify the S. aureus infection spread.

Differential Virulence of Aggregatibacter actinomycetemcomitans Serotypes Explained by Exoproteome Heterogeneity

“…It is important to note here that different mechanisms have been implicated in the release of ECPs into the extracellular milieu, including cell death, autolysis, membrane weakening by toxins, and cell lysis due to the induction of prophages ( 45 – 47 ). For S. Aureus , it was also reported that upregulation of the cell division protein FtsA promoted the release of the cytoplasmic proteins into the growth medium, and it was proposed that the excretion of cytoplasmic proteins coincided with the moment of cell division when the bacterial cell integrity may be partially compromised ( 48 ). In our present study, we detected the FtsA protein only in the medium of the 25R isolate, which makes it difficult to correlate FtsA to the detection of ECPs.…”

Thirty Years of sRNA-Mediated Regulation in Staphylococcus aureus: From Initial Discoveries to In Vivo Biological Implications

“…Few proteins were evidenced as potential targets of SprF1, as their expressions were downregulated when SprF1 was overexpressing. Some are glycolysis-related proteins, of which three have reduced the transcript levels in intracellular persisters [101,102]. In silico analyses predicted a potential interaction between SprF1 and the ppiB mRNA target, but this hypothesis was not further validated by the EMSA experiments [101].…”

“…This novel discovery may serve as a starting point for the development of sRNA-based therapies if it is confirmed in vivo (within the host). Potential SprF1 targets were also screened [101]. Few proteins were evidenced as potential targets of SprF1, as their expressions were downregulated when SprF1 was overexpressing.…”