Quorum sensing is a widespread process in bacteria that controls collective behaviours in response to cell density. Populations of cells coordinate gene expression through the perception of self-produced chemical signals. Although this process is well-characterized genetically and biochemically, quantitative information about network properties, including induction dynamics and steady-state behaviour, is scarce. Here we integrate experiments with mathematical modelling to quantitatively analyse the LasI/LasR quorum sensing pathway in the opportunistic pathogen Pseudomonas aeruginosa. We determine key kinetic parameters of the pathway and, using the parametrized model, show that quorum sensing behaves as a bistable hysteretic switch, with stable on and off states. We investigate the significance of feedback architecture and find that positive feedback on signal production is critical for induction dynamics and bistability, whereas positive feedback on receptor expression and negative feedback on signal production play a minor role. Taken together, our data-based modelling approach reveals fundamental and emergent properties of a bacterial quorum sensing circuit, and provides evidence that native quorum sensing can indeed function as the gene expression switch it is commonly perceived to be.
Keywords: Pseudomonas aeruginosa; bistability; feedback; mathematical modelling; quorum sensing.