Some clinical isolates of Staphylococcus aureus produce the superantigenic toxic shock syndrome toxin TSST-1, encoded by tst and located on pathogenicity islands. The expression of tst is complex, and influenced by environmental conditions such as pH, CO2 and glucose. We identified a putative catabolite responsive element (cre) in the promoter region of all known tst genes, indicating that tst transcription may be regulated by the catabolite control protein CcpA. By introducing tst-genes under their native promoter or tst-promoter-reporter gene fusions in wild type strain Newman, we showed that glucose was able to repress tst transcription and TSST-1 production, whereas glucose repression was abolished in the corresponding DeltaccpA mutant. Stabilizing the pH ruled out a pH effect due to acid production during glucose catabolism. CcpA thus directly regulates tst transcription, linking carbohydrate utilization to virulence gene expression in S. aureus.