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Our previous studies suggested that the essential two-component signal transduction system, YhcSR, regulates the  opuCABCD  operon at the transcriptional level, and the  Pspac -driven  opuCABCD  partially complements the lethal effects of  yhcS  antisense RNA expression in  Staphylococcus aureus . However, the reason why  yhcSR  regulon is required for growth is still unclear. In this report, we present that the  lac  and  opuC  operons are directly transcriptionally regulated by YhcSR. Using real-time RT-PCR we showed that the down-regulation of  yhcSR  expression affected the transcription of  lacA  encoding galactose-6-phosphotase isomerase subunit LacA, and  opuCA  encoding a subunit of a glycine betaine/carnitine/choline ABC transporter. Promoter- lux  reporter fusion studies further confirmed the transcriptional regulation of  lac  by YhcSR. Gel shift assays revealed that YhcR binds to the promoter regions of the  lac  and  opuC  operons. Moreover, the  Pspac -driven  lacABC  expression  in trans  was able to partially complement the lethal effect of induced  yhcS  antisense RNA. Likewise, the  Pspac -driven  opuCABCD  expression  in trans  complemented the growth defect of  S. aureus  in a high osmotic strength medium during the depletion of YhcSR. Taken together, the above data indicate that the  yhcSR  system directly regulates the expression of  lac  and  opuC  operons, which, in turn, may be partially associated with the essentiality of  yhcSR  in  S. aureus . These results provide a new insight into the biological functions of the  yhcSR , a global regulator.

The Essential yhcSR Two-Component Signal Transduction System Directly Regulates the lac and opuCABCD Operons of Staphylococcus aureus