The Role of Regulators in the Expression of Quorum-Sensing Signals in <i>Pseudomonas aeruginosa</i>

Quorum-sensing systems provide Pseudomonas aeruginosa with a sensitive regulatory mechanism that allows for the induction of several phenotypic genes in a cell density fashion. In this work, a mathematical model of the acylated homoserine lactones regulatory network system in P. aeruginosa has been developed. It is the first integrated model to consider both quorum-sensing systems. The model has allowed us to disentangle the complex behavior exhibited by the system as the concentration of extracellular OdDHL is increased. At either low or high levels of extracellular OdDHL, the bacterium remains in an uninduced or induced state, respectively. At moderate levels, the behavior is characterized by several states. Here, the bacteria can switch suddenly from an uninduced to an induced phenotype in response to small changes in the concentration of extracellular OdDHL. Additionally, we have been able to address the roles of RsaL and Vfr as regulators of the quorum-sensing system. An important result from this analysis suggests that RsaL will increase the concentration of extracellular OdDHL required to induce the system, and it is a key regulator of the inhibition of the quorum-sensing system under low cell densities. Most importantly, our results suggest that Vfr has strong regulatory effects on the system as an increased affinity between the LasR/OdDHL complex, and the lasR promoter leads to significant qualitative changes in induction patterns. We also show experimental data that demonstrate that Vfr is required for signal production in the early phase of growth, but that in the latter stages of growth, the vfr mutant is able to synthesize wild-type levels of signal.