Staphylococcus aureus causes a wide spectrum of infections in humans. Virulence in S. aureus is mediated by cell wall-associated and secreted proteins. Cell wall-associated proteins enable the bacteria to adhere to tissue components. Our studies have focused on the contribution to virulence of bacterial surface adhesins, such as the fibrinogen-binding protein, or clumping factor A (ClfA), and the fibronectin-binding protein A (FnbA), using a gene transfer approach. Our current work addressed how these proteins interact in the initiation and further development of the infection process.