Uncovering quorum sensing and quenching structural properties: a systems biology approach

Bacteria have the ability to coordinate their behavior in a cell density-dependent manner by using diffusible signal molecules. The mechanism, known as quorum sensing, is a cell-to-cell communication process exploited either by pathogens to regulate the expression of virulence and antimicrobial resistance-related genes and by synthetic biologists to engineer bacterial density-dependent functions. Using a systems biology approach, we developed a novel quorum sensing mathematical model and performed a comprehensive study of the equilibrium properties of this communication process. This analysis highlighted crucial structural properties as a result of bistability in the genetic circuit and underlined that bacteria exploit feedback control strategies to produce a unified and robust response. Due to increased antibiotic-resistant infections, researchers investigated enzymatic methods to interfere with quorum sensing. In this paper, we simulated two quorum quenching strategies. Using a modeling approach, we discovered core parameter values which guarantee the effectiveness of these strategies and could be exploited in rational design of synthetic biology based engineered bacteria.