The present invention relates to methods of inducing an immune response to Staphylococcus comprising administering a composition comprising an SA2493-related polypeptide from Staphylococcus aureus as well as derivatives or fragments thereof. The present invention also encompasses methods of treating and/or reducing the likelihood of a Staphylococcus infection by administering a composition comprising an SA2493-related polypeptide or an antibody that specifically binds to an SA2493 polypeptide, derivative or fragments thereof. Compositions administered in the methods of the invention can include one or more additional antigens including, but not limited to, IsdB. Compositions used to practice the methods of the invention are also encompassed.