Disclosed are antisense molecules and compositions for the treatment of Staphylococcus aureus infection. The antisense molecules and compositions comprise nucleic acid molecules, such as RNA, DNA, or nucleic acid molecules with modified backbones, such as PNA. The antisense molecules and compositions inhibit gene expression in Staphylococcus aureus; are optionally conjugated to cell penetration molecules such as peptides; and are optionally administered in the form of a nanoparticle composition.