Environmental regulation of virulence determinant expression in Staphylococcus aureus
Staphylococcus aureus is a highly versatile pathogen that causes a wide range of diseases. Appropriate gene expression in various niches within the human body and abiotic environments requires the sensing of environmental conditions. An important environmental parameter affecting S. aureus is NaC1 concentration. This study investigated S. aureus virulence determinant regulation in the presence and absence of NaCl stress. In the absence of NaCl stress, aB was found to repress hla transcription and protease activity, possibly via the repression of agr transcription. The effect of aB on agr probably occurs indirectly, although sarA, sarHi and rot are unlikely to function as intermediates in this pathway. Tn551 mutagenesis identified numerous genes, including lysC, ykuQ, lysA, brnQ and telA, which repress hla transcription and protease activity by upregulating aB activity. These genes are clustered in the SVS (S. aureus virulence and survival) region of the S. aureus genome, in which transposon insertion affected the virulence and survival of mutants isolated in numerous published screens. Other SVS region genes, including asd, dapA, hipO, ac1P and norQ were also found to repress hla transcription and protease activity by upregulating aB activity. In the presence of NaCl stress, virulence determinants (which are normally regulated by agr) come under the control of a novel regulatory system involving an-dependent and aB-independent pathways. Tn917 mutagenesis identified several genes, including citG, opuD, yugT, oppF, ykrP, eprH, yubA, unkl and unk2, which have putative roles in the aB-independent pathway. The SVS region genes analysed may function in the aB- dependent pathway. The sensor saeS was found to upregulate hla transcription in the absence of NaCI stress and may be involved in sensing NaCI stress. The NaCI stress signal may act in concert with other parameters to allow stringent virulence determinant regulation in response to the prevailing environmental conditions.