Abstract: Provided herein is a method for identifying small molecule inhibitors of S. aureus SdrD protein attachment to a host cell receptor using a structural model of SdrD protein-receptor interaction. Also provided are the small molecule inhibitors so identified and synthetic small molecules effective to bind SdrD protein and/or the host cell receptor. In addition, antibodies directed against SdrD protein are provided. Further provided are methods of treating or preventing S. aureus associated lung infections and of inhibiting S. aureus adherence to a lung cell using the small molecules and antibodies described herein.