Quorum Activation at a Distance: Spatiotemporal Patterns of Gene Regulation from Diffusion of an Autoinducer Signal

Abstract

Quorum sensing (QS) bacteria regulate gene expression collectively by exchanging diffusible signal molecules known as autoinducers. Although QS is often studied in well-stirred laboratory cultures, QS bacteria colonize many physically and chemically heterogeneous environments where signal molecules are transported primarily by diffusion. This raises questions of the effective distance range of QS and the degree to which colony behavior can be synchronized over such distances. We have combined experiments and modeling to investigate the spatiotemporal patterns of gene expression that develop in response to a diffusing autoinducer signal. We embedded a QS strain in a narrow agar lane and introduced exogenous autoinducer at one terminus of the lane. We then measured the expression of a QS reporter as a function of space and time as the autoinducer diffused along the lane. The diffusing signal readily activates the reporter over distances of ~1 cm on time scales of ~10 h. However, the patterns of activation are qualitatively unlike the familiar spreading patterns of simple diffusion, as the kinetics of response are surprisingly insensitive to the distance the signal has traveled. We were able to reproduce these patterns with a mathematical model that combines simple diffusion of the signal with logistic growth of the bacteria and cooperative activation of the reporter. In a wild-type QS strain, we also observed the propagation of a unique spatiotemporal excitation. Our results show that a chemical signal transported only by diffusion can be remarkably effective in synchronizing gene expression over macroscopic distances.