Infection-mimicking conditions alter expression patterns of the highly abundant extracellular protease Jep in a mouse-adapted Staphylococcus aureus strain.

The opportunistic pathogen Staphylococcus aureus colonizes a broad spectrum of different hosts and intra-host niches. Recently, it has been demonstrated that mouse-adapted S. aureus strains are better suited to investigate S. aureus infections in the mouse model than human-adapted strains. One of the most studied mouse-adapted strains is JSNZ (CC88-MSSA). Under control conditions at 37 °C, JSNZ secretes very large amounts of the prophage-encoded serine protease Jep (JSNZ extracellular protease). Given S. aureus' ability to colonize a broad variety of host niches, we investigated Jep expression at transcript and protein levels under several physiological conditions, such as different temperatures (37 °C, 42 °C and 32 °C), and infection-relevant stress conditions (iron and oxygen limitation). Gene expression and protein abundance of Jep differed between the different conditions, with elevated levels at 42 °C and under iron limitation and reduced levels at 32 °C and under oxygen limitation. Mass spectrometry analysis proved that Jep is the major protein in the JSNZ supernatant making up to 75% at 37 °C and 42 °C, as well as under iron limitation. In silico predictions and Northern blot analyses revealed that jep is encoded as a monocistronic transcript of approximately 900 bp, showing prophage-independent regulation. Correlation analysis of protein abundances and additional in silico analysis suggest SaeR and PurR as potential regulators of jep. To extend these observations to a pathophysiological context, we additionally examined Jep abundance in a murine infection model and found it to be the most abundant secreted protein there as well.