Characterizing the Dynamics of the Quorum-Sensing System in <i>Staphylococcus aureus</i>

Abstract

The virulence determinants of <i>Staphylococcus aureus</i> are expressed in a growth phase-dependent manner governed by the autoinducible quorum-sensing system <i>agr</i>. Activation of the <i>agr</i> system results in a rapid increase in the regulator RNAIII and occurs in response to accumulation of AIP. In order to activate the <i>agr</i> system, a basal transcription of <i>agr</i> components must be assumed. This basal transcription of <i>agr</i> components seems to be stimulated by <i>sarA</i>. To better understand how SarA would affect activation of the <i>agr</i> system by modulating the basal <i>agr</i> activity, a mathematical model for autoactivation of the <i>agr</i> system was set up. The model predicted that the <i>agr</i> system is hysteretic, meaning that the <i>agr</i> 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 <i>agr</i> 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 <i>S. aureus</i> mutants with different levels of SarA expression. Since natural antagonistic AIPs have been demonstrated, the effect of adding inhibitors to the system was analyzed.