Staphylococcus aureus is a major human pathogen. Superantigens (SAg) are important virulence factors in S. aureus, but the regulation of SAg gene expression is largely unknown. Using 2 sequenced S. aureus strains (COL and Newman) and 4 clinical isolates, regulation of gene expression was investigated in more detail for 12 SAgs. The SAg-encoding genes were expressed in a growth phase-dependent manner: while the egc operon was mainly transcribed at low optical densities, the transcription of seb was induced at high optical densities. The transcript levels of sea, sek, seq, sep, and tst-1 did not change significantly during growth. The T cell-mitogenic activity of supernatants correlated with the transcription data. SaeRS and σ(B) strongly influenced SAg gene transcription. σ(B) activated transcription of seh, tst-1, and of the egc operon. A possible σ(B)-dependent promoter was identified in front of the egc operon. In contrast, a loss of σ(B) enhanced the transcript level of seb, suggesting an indirect effect of the alternative sigma factor on the transcription of this gene. Transcriptional studies of an saeS mutant showed that the two-component system only activates transcription of seb. The influence of σ(B) and SaeRS on the expression of SAg genes was validated by T cell proliferation assays. For sigB mutants in different strains, different effects on the T cell-mitogenic potential were observed depending on the SAg gene repertoire of the isolates.
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