The Evolution of Quorum Sensing in Bacterial Biofilms

Abstract

Bacteria have fascinating and diverse social lives. They display coordinated group behaviors regulated by quorum-sensing systems that detect the density of other bacteria around them. A key example of such group behavior is biofilm formation, in which communities of cells attach to a surface and envelope themselves in secreted polymers. Curiously, after reaching high cell density, some bacterial species activate polymer secretion, whereas others terminate polymer secretion. Here, we investigate this striking variation in the first evolutionary model of quorum sensing in biofilms. We use detailed individual-based simulations to investigate evolutionary competitions between strains that differ in their polymer production and quorum-sensing phenotypes. The benefit of activating polymer secretion at high cell density is relatively straightforward: secretion starts upon biofilm formation, allowing strains to push their lineages into nutrient-rich areas and suffocate neighboring cells. But why use quorum sensing to terminate polymer secretion at high cell density? We find that deactivating polymer production in biofilms can yield an advantage by redirecting resources into growth, but that this advantage occurs only in a limited time window. We predict, therefore, that down-regulation of polymer secretion at high cell density will evolve when it can coincide with dispersal events, but it will be disfavored in long-lived (chronic) biofilms with sustained competition among strains. Our model suggests that the observed variation in quorum-sensing behavior can be linked to the differing requirements of bacteria in chronic versus acute biofilm infections. This is well illustrated by the case of Vibrio cholerae, which competes within biofilms by polymer secretion, terminates polymer secretion at high cell density, and induces an acute disease course that ends with mass dispersal from the host. More generally, this work shows that the balance of competition within and among biofilms can be pivotal in the evolution of quorum sensing. Bacteria are increasingly recognized as highly interactive organisms with complex social lives, which are critical to their capacity to cause disease. In particular, many species inhabit dense, surface-bound communities, termed biofilms, within which they communicate and respond to local cell density through a process known as quorum sensing. Enormous effort has been devoted to understanding the genetics and biochemistry of biofilm formation and quorum sensing, but how and why they evolve remain virtually unexplored. Many bacteria use quorum sensing to regulate the secretion of sticky extracellular slime, an integral feature of biofilm life. Intriguingly, however, some pathogenic species turn on slime production at high cell density, whereas others turn it off. Using an individual-based model of biofilm growth, we investigated why different species use quorum sensing to control slime production in opposite ways. The secret underlying this variation appears to reside in the nature of infections. Turning slime on at high cell density can allow one strain to suffocate another when competition is intense, as occurs in long-lived chronic infections. Meanwhile, turning slime secretion off at high cell density can benefit a strain causing an acute infection by allowing rapid growth before departing the host.