A Functional ClpXP Protease is Required for Induction of the Accessory Toxin Genes, tst, sed, and sec.

Staphylococcal toxic shock syndrome is a potentially lethal illness attributed to superantigens produced by Staphylococcus aureus, in particular toxic shock syndrome toxin 1 (TSST-1), but staphylococcal enterotoxins (SEs) are also implicated. The genes encoding these important toxins are carried on mobile genetic elements, and the regulatory networks controlling expression of these toxins remain relatively unexplored. We show here that the highly conserved ClpXP protease stimulates transcription of tst (TSST-1), sec (SEC), and sed (SED) genes in the prototypical strains, SA564 and RN4282. In the wild-type cells, the post-exponential upregulation of toxin gene transcription was proposed to occur via RNAIII-mediated downregulation of the Rot repressor. Contradictive to this model, we showed that the post-exponential induction of tst, sed, and sec transcription did not occur in cells devoid of ClpXP activity, despite the Rot level being diminished. To identify transcriptional regulators with a changed expression in cells devoid of ClpXP activity, RNA sequencing was performed. The RNAseq analysis revealed a number of global virulence regulators that might act downstream of ClpXP, to control expression of tst and other virulence genes. Collectively, the results extend our understanding of the complex transcriptional regulation of the tst, sed, and sec genes.