Quorum Sensing in Bacteria: We Two Are One

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Quorum sensing is the ability of bacteria to communicate and coordinate behavior via signaling molecules. The reason for these systems seem to have evolved is to coordinate behaviours or actions between individual bacterial cells depending on their number. For example, opportunistic bacteria can grow within a host without harming it, until they reach a certain concentration. When their numbers are sufficient to overcome the host’s immune system, they change their behavior and cause disease.

The first organisms in which quorum sensing was observed were Myxobacteria and Streptomyces species. However, the most popular example of quorum sensing is the regulation of light production in Vibrio fischeri, a bioluminiscent (glow in the dark) bacterium that lives as a symbiont in the light-producing organ of the Hawaiian bobtail squid(!). In the 1960s it was discovered that when Vibrio fischeri cells are free-living, the autoinducer is present at low concentration and so the cells do not luminesce. In the light organ of the squid, they are highly concentrated and transcription of the luciferase gene is induced, leading to bioluminescence.

Bacteria which use quorum sensing produce and secrete signaling compounds called autoinducers. These bacteria also have a receptor which can specifically detect the inducer. When the inducer binds to it’s receptor, it activates transcription of certain genes, including those for inducer synthesis. When only a few other bacteria of the same kind are in the vicinity, diffusion reduces the concentration of the inducer in the surrounding medium, so the bacteria produce little inducer. With high concentrations of bacteria, the concentration of the inducer passes a threshold, so more inducer is synthesised. This forms a positive feedback loop, and the receptor becomes fully activated.

Two chemically different autoinducers are involved in regulation, autoinducer-1 and autoinducer-2. An interesting observation is that autoinducer-2 is conserved among many different bacterial species, including Escherichia coli and other enteric bacteria. Because of this, autoinducer-2 is used for interspecies communication. The discovery that bacteria are able to communicate with each other changed our general perception of many isolated, simple organisms inhabiting our world. Both Gram-positive and Gram-negative bacteria use quorum sensing to regulate a diverse array of physiological activities. These processes include symbiosis, virulence, competence, conjugation, antibiotic production, motility, and spore and biofilm formation (Miller MB, Bassler BL. Quorum sensing in bacteria. Ann Rev Microbiol. 2001 55: 165-199).

Although the actual chemical signals, signal relay mechanisms, and the target genes controlled by bacterial quorum sensing systems differ, the ability to communicate with one another allows bacteria to coordinate their gene expression, and therefore the behavior of the entire community. Many bacteria can form multicellular aggregates on surfaces called biofilms, where they are protected against agents such as antibiotics or antibodies. Bacteria organized in biofilms are very difficult to control and often even high dosages
of antibiotics cannot clear infectious biofilms, for example on implanted medical devices. To form biofilms bacteria need to start a complicated genetic program to switch from a free-living planktonic lifestyle to a sessile existence. This starts with determination of their cell density by means of quorum sensing. From the structure of quorum sensing autoinducers, several derivatives have been developed which prevent biofilm formation in many Gram-positive bacteria, including Staphylococcus aureus, a particular problem in hospitals. Some of these compounds are already in clinical studies (Abraham WR. Controlling biofilms of gram-positive pathogenic bacteria. Curr Med Chem. 2006 13: 1509-24).

Microorganisms communicate and cooperate to perform a wide range of multicellular behaviours, such as nutrient acquisition, biofilm formation through quorum sensing. These complex multicellular behaviours are interesting from the perspective of social evolution - why do microorganisms engage in these behaviours given that cooperative individuals can be exploited by selfish cheaters, who gain the benefit of cooperation without paying their share of the cost? A new paper just published describes an overview of the different mechanisms through which cooperative behaviours can be stabilized, the novel problems that microorganisms pose and the new insights that can be gained from applying evolutionary theory to microorganisms (West SA, et al. Social evolution theory for microorganisms. Nat Rev Microbiol. 2006 4: 597-607).

Quorum sensing is providing a new dimension to our understanding of how complex micro-organisms really are.

Links:

• The Quorum Sensing Site
• Wikipedia: Quorum Sensing