Determinants of Staphylococcus aureus Colonization and Infection. “Exploring the Role of Cell Wall Anchored Proteins in Adhesion and Immune Evasion”

Abstract

Staphylococcus aureus is an efficient human colonizer and pathogen. S.aureus' ability to colonize and/or cause infections in humans is due to its expression of many virulence factors. These virulence factors aid the bacterium in adhering, invading and evading the host´s immune defences. This study focused on exploring the role of two cell wall anchored proteins: Serine-aspartate containing protein D (SdrD) and S. aureus surface protein G (SasG) in S. aureus adhesion and/or immune evasion. First, we identified Desmoglein 1 (Dsg1) as a host ligand for S. aureus SdrD. Desmogleins are part of the intercellular junctions that facilitate adhesion between the keratinocytes of the epidermis. We showed that the interaction between Dsg1 and SdrD is specific and dose-dependent. In addition, we showed that deletion of sdrD in S. aureus NCTC8325-4 attenuated the bacterial adhesion to Dsg1 expressing cells. Using Lactobacillus lactis expressing SdrD, we further confirmed that SdrD mediated bacterial adhesion to keratinocytes. Furthermore, we showed genetic variability within A region sequences of the sdrD gene of S. aureus strains isolated from the anterior nares of healthy adults. We classified the sdrD variants into seven types and showed that the variations occurred within other regions of the SdrD protein. However, the N2-N3-B1 subdomains and R domain of SdrD have the most variations. The variations within the N2-N3-B1 subdomains were surface associated. Functional analyses using in vitro cell adhesion assay showed a significant difference between two of the sdrD variants. In addition, we showed SasG promoted bacterial adhesion to human keratinocytes. In human blood, sasG expression was upregulated. Serum components induced early expression of SasG in a bacteriological medium. However, SasG did not promote the bacterial survival in an ex vivo human blood model but promoted bacterial aggregation when serum components were present. Our findings show that both SdrD and SasG are involved in adhesion and that the mechanisms involved in S. aureus interaction with the host are complex. Additional studies are required to further understand the complete functions of these S. aureus virulence factors.