Characterizing the dynamics of the quorum-sensing system in Staphylococcus aureus.

The virulence determinants of Staphylococcus aureus are expressed in a growth phase-dependent manner governed by the autoinducible quorum-sensing system agr. Activation of the agr system results in a rapid increase in the regulator RNAIII and occurs in response to accumulation of AIP. In order to activate the agr system, a basal transcription of agr components must be assumed. This basal transcription of agr components seems to be stimulated by sarA. To better understand how SarA would affect activation of the agr system by modulating the basal agr activity, a mathematical model for autoactivation of the agr system was set up. The model predicted that the agr system is hysteretic, meaning that the agr system is activated at a specific concentration of autoinducing peptide (AIP), whereas it is inactivated at a specific lower concentration of AIP. According to the model, changing the basal agr activity only had a marginal effect on steady-state levels of RNAIII but changed the sensitivity of the cells to AIP. This was supported by Northern blot analysis of RNAIII in S. aureus mutants with different levels of SarA expression. Since natural antagonistic AIPs have been demonstrated, the effect of adding inhibitors to the system was analyzed.