Noise Reduction by Diffusional Dissipation in a Minimal Quorum Sensing Motif

Cellular interactions are subject to random fluctuations (noise) in quantities of interacting molecules. Noise presents a major challenge for the robust function of natural and engineered cellular networks. Past studies have analyzed how noise is regulated at the intracellular level. Cell–cell communication, however, may provide a complementary strategy to achieve robust gene expression by enabling the coupling of a cell with its environment and other cells. To gain insight into this issue, we have examined noise regulation by quorum sensing (QS), a mechanism by which many bacteria communicate through production and sensing of small diffusible signals. Using a stochastic model, we analyze a minimal QS motif in Gram-negative bacteria. Our analysis shows that diffusion of the QS signal, together with fast turnover of its transcriptional regulator, attenuates low-frequency components of extrinsic noise. We term this unique mechanism “diffusional dissipation” to emphasize the importance of fast signal turnover (or dissipation) by diffusion. We further show that this noise attenuation is a property of a more generic regulatory motif, of which QS is an implementation. Our results suggest that, in a QS system, an unstable transcriptional regulator may be favored for regulating expression of costly proteins that generate public goods.Author Summary: Quorum sensing (QS) is a mechanism by which many bacteria regulate gene expression via the synthesis and detection of small, diffusible signals. Since its discovery, QS has been shown to control diverse physiological functions in numerous types of bacteria. It provides an elegant strategy for bacteria to sense their density and to achieve coordinated population behavior. By stochastic modeling, we show that QS can effectively reduce variability (“noise”) in the expression of its target genes. Surprisingly, the noise reduction does not significantly depend on the number of bacteria but rather results from the coupling of a bacterium and its environment through signal diffusion. Diffusion enables fast signal turnover, which, together with fast intracellular turnover of the cognate receptor of the signal, leads to noise reduction. Our work suggests a unique role of QS in achieving robust gene regulation, which is distinct from noise-regulation mechanisms that act at the intracellular level. As such, it offers novel insights into evolution of QS as well as its application in construction of synthetic gene circuits.