Functional Analysis of Staphylococcus Aureus Secretion Chaperone Prsa and Its Roles in Regulating Protein a Secretion

Staphylococcus aureus is an important community and nosocomial-associated pathogen, which produces and exports many virulence factors to cause human diseases. As is generally known, proteins are transported across the membrane in an unfolded state. After membrane translocation, the proteins need to be folded into its correct conformation to prevent them from degradation by quality control proteases, which are present in the interface between cytoplasmic membrane and cell wall. PrsA, a membrane-bound foldase found ubiquitously in Gram-positive bacteria, assists post-translocational folding of exported proteins. However, the role of PrsA in S. aureus is unclear. Our earlier studies found that deletion in prsA enhanced auto-aggregation and the cells tended to clump and precipitate at the bottom of the culture tubes. In a mice infection model, the mice infected with a prsA-knockout strain had higher survival rate than that of the mice infected with the wild-type strain. Deleting the prsA gene promotes bacterial survival in the hosts, resulting in persistent infection, increased bacterial loads and abscess formation in the organs of infected mice. Furthermore, immune response assay showed that the wild-type strain elicits more cytokines production in mice than a prsA-deficient strain. Additionally, PrsA is required for the secretion of protein A, which is a virulent factor of S. aureus and involved in host immune evasion. The preliminary results from this study indicated that PrsA plays an important role in pathogenesis of S. aureus. This study hypothesizes that PrsA influences cell surface properties and is required for the post-translocational folding of protein A. During infection, the wild-type strain which expresses PrsA and protein A may induce immune storm, which subsequently causes death of infected mice. Moreover, the wild-type strain is eliminated easily by the host immune system even though the bacteria escape from the immune storm. By contrast, the prsA-deficient strain, which lacks protein A, is being taken up by phagocytes and the engulfed bacteria may be resistant to intracellular killing and survive in the cells, which cause persistent infection. Accordingly, the objectives of this study are (1) studying how PrsA affects the surface properties of S. aureus; (2) investigating how PrsA influences secretion of protein A; (3) elucidating the impacts of PrsA deficiency on protein A-mediated functions. The information derived from this study will provide new insights into the protein export pathways that are crucial to pathogenesis of S. aureus.

Project ID:PC10507-0253
External Project ID:MOST105-2320-B182-027-MY3