Exoproteome profiling reveals the involvement of the foldase PrsA in the cell surface properties and pathogenesis of S. aureus

Staphylococcus aureus is a bacterial pathogen that produces and exports many virulence factors that cause human diseases. PrsA, a membrane-bound foldase that is found ubiquitously in Gram-positive bacteria, is required for the folding of exported proteins into a stable and active structure. However, the involvement of PrsA in post-translocational protein folding in S. aureus remains unclear. In this study, a PrsA-deficient mutant of S. aureus HG001 was constructed and prsA deletion was shown to enhance auto-aggregation and increase the ability of S. aureus HG001 to adhere to human lung epithelial cells. The lack of PrsA made the bacteria more sensitive to sonication-induced lysis. In a mouse infection model, mice that were infected with a prsA-knockout strain HG001ΔprsA had a higher survival rate than those infected with the wild-type strain. An iTRAQ-based quantitative exoproteome analysis was conducted to identify the proteins whose secretion was affected by PrsA. The exoproteomic analysis revealed that prsA deletion altered the amounts of several proteins that were related to the properties of the cell surface and virulence. These include proteins involved in cellular adhesion and cell wall synthesis such as extracellular adhesion protein (Eap), undecaprenyl-diphosphatase (UppP) and FmtA, and proteins involved in subverting host innate immunity such as immunoglobulin-binding proteins Spa and Sbi, chemotaxis inhibitory protein (CHIP) and staphylococcal complement inhibitor (SCIN). The results of this study suggested that PrsA is required for the post-translocational folding of many exported proteins and critically affects the cell surface properties and pathogenesis of S. aureus.