The languages of bacteria.

Bacteria communicate with one another using chemical signaling molecules as words. Specifically, they release, detect, and respond to the accumulation of these molecules, which are called autoinducers. Detection of autoinducers allows bacteria to distinguish between low and high cell population density, and to control gene expression in response to changes in cell number. This process, termed quorum sensing, allows a population of bacteria to coordinately control the gene expression of the entire community. Quorum sensing confuses the distinction between prokaryotes and eukaryotes because it allows bacteria to behave as multicellular organisms, and to reap benefits that would be unattainable to them as individuals. Many bacterial behaviors are regulated by quorum sensing, including symbiosis, virulence, antibiotic production, and biofilm formation. Recent studies show that highly specific as well as universal quorum sensing languages exist which enable bacteria to communicate within and between species. Finally, both prokaryotic and eukaryotic mechanisms that interfere with bacterial quorum sensing have evolved. Specifically, the secretion of enzymes that destroy the autoinducers, and the production of autoinducer antagonists, are used by competitor bacteria and susceptible eukaryotic hosts to render quorum sensing bacteria mute and deaf, respectively. Analogous synthetic strategies are now being explored for the development of novel antimicrobial therapies. Bacteria in communities convey their presence to one another by releasing and responding to the accumulation of chemical signaling molecules called autoinducers. This process of intercellular communication, called quorum sensing, was first described in the bioluminescent marine bacterium Vibrio fischeri (Hastings and Nealson 1977; Nealson and Hastings 1979). V. fischeri lives in symbiotic associations with a number of marine animal hosts. In these partnerships, the host uses the light produced by V. fischeri for specific purposes such as attracting prey, avoiding predators, or finding a mate. In exchange for the light it provides, V. fischeri obtains a nutrient-rich environment in which to reside (Ruby 1996; Visick and McFall-Ngai 2000). A luciferase enzyme complex is responsible for light production in V. fischeri. Bioluminescence only occurs when V. fischeri is at high cell number, and this process is controlled by quorum sensing. Specifically, the production and accumulation of, and the response to, a minimum threshold concentration of an acylated homoserine lactone (HSL) autoinducer regulates density-dependent light production in V. fischeri, and enables V. fischeri to emit light only inside the specialized light organ of the host but not when free-living in the ocean. The reason for this is twofold. First, only under the nutrient-rich conditions of the light organ can V. fischeri grow to high population densities, and second, trapping of the diffusible autoinducer molecule in the light organ with the bacterial cells allows it to accumulate to a sufficient concentration that V. fischeri can detect it. Engebrecht and Silverman discovered the regulatory circuit controlling quorum sensing in V. fischeri (Engebrecht et al. 1983; Engebrecht and Silverman 1984, 1987). They showed that two regulatory components are required for the process. The LuxI protein is responsible for production of the HSL autoinducer, and the LuxR protein is responsible for binding the HSL autoinducer and activating transcription of the luciferase structural operon at high cell density (Engebrecht et al. 1983; Engebrecht and Silverman 1984). They showed that, as an autoinducer-producing population of V. fischeri cells grows, the concentration of autoinducer increases as a function of increasing cell-population density. When the autoinducer concentration reaches the micromolar range, it can interact with the LuxR protein, and the LuxR-autoinducer complex binds the luciferase promoter to activate transcription. Therefore, this quorum sensing circuit allows light production to be tightly correlated with the cell population density. For over 10 years the V. fischeri LuxI/LuxR signal–response system was considered a curious, but isolated, example of bacterial communication that had presumably evolved for a specific purpose required for the colonization of a symbiotic host. However, we now understand that most bac1Corresponding author. E-MAIL bbassler@molbio.princeton. edu; FAX (609) 258–6175. Article and publication are at http://www.genesdev. org/cgi/doi/10.1101/ gad.899601.