Quorum sensing

Quorum sensing is the ability of populations of bacteria to communicate and coordinate behavior via signaling molecules which are often small peptides or homoserine lactones.

A general name for quorum sensing signaling compounds is autoinducer, refering to their ability to trigger gene expression in the cells (autoinduction) of the same species that produce the compound. Pheromone is another term with a very similar meaning to autoinducer.

In Gram negative bacteria, at least two main classes of autoinducer have been defined, namely AI-1 and AI-2. AI-1s are various forms of acyl homoserine lactones (AHLs). AHLs are synthesized from acyl carrier proteins by LuxI-type AHL synthases. The enzyme producing AI-2 is called called LuxS, which forms the molecule 4,5-dihydroxy-2,3-pentanedione (DPD) that undergoes a variety of spontaneous rearrangements which generate different AI-2 compounds.

In Gram positive bacteria such as Bacillus and Enterococcus, autoinducers are usually short peptides.

General biological function of quorum sensing

A major function of quorum sensing is to coordinate certain behaviour or actions between bacteria of the same kind, depending on their number. The use of the word quorum is an allusion to the attendance numbers required for valid business meetings that legally require a "quorum".

An example of bacterial coordination is when opportunistic bacteria, such as Pseudomonas aeruginosa can grow within a host without harming it, until they reach a certain concentration. Then at a certain cell density (the quorum) they can channel their activities into activities (such as specialised biofilm formation and immune system suppression where the presence of large number of cooperating bacteria may overwhelm the large host.

It is hoped that the therapeutic useful enzymatic degradation of the signalling molecules might be used prevent the formation of bacterial biofilms and possibly weaken established biofilms. Disrupting the signalling process in this way is called quorum quenching.

Role of quorum sensing in specific organisms

Quorum sensing has been implicated in many different microorganisms as a mechanism for triggering of a wide range of complex or highly evolved responses whose effectiveness depends on large numbers of cells with the same capabilities working together in a particular location. These include :

• Bioluminescence by Vibrio bacteria, discovered in the 1970s
• Mating ability of the Gram positive coccus Enterococcus faecalis, Clewell, 1975
• Cytolysin (virulence factor) production by Enterococcus
• Antibiotic production by various Streptomyces and Erwinia bacteria
• Fruiting body production by Myxococcus bacteria
• Virulence, biofilm formation by Pseudomonas aeruginosa
• Biofilm formation ability coded by F factor in Escherichia coli
• Virulence in Vibrio cholerae
• DNA injection into plants by Agrobacterium tumefaciens]
• Erwinia bacteria's virulence for plants
• DNA uptake (transformation) competence in Streptococcus pneumoniae
• Competence for DNA transformation , spore formation in Bacillus
• Staphylococcus aureus virulence

The first organisms in which quorum sensing was observed were Myxobacteria and Streptomyces species. However, the most well known (and beautiful) example is the regulation of light production in Vibrio fischeri, a bioluminiscent bacterium that lives as a symbiont in the light-producing organ of the Hawaiian bobtail squid. When V. fischeri cells are free-living, the autoinducer is at low concentration and thus cells do not luminesce. In the light organ of the squid (photophore), they are highly concentrated (about 10¹¹ cells/ml) and transcription of luciferase is induced, leading to bioluminescence.

Processes possibly regulated or partially regulated by AI-2-mediated quorum sensing in E. coli include cell division. In other species such as Pseudomonas aeruginosa quorum-related processes include biofilm development, exopolysaccharide production, and cell aggregation. AI-2 was found to increase expression of sdiA, a transcriptional regulator of promoters which promote ftsQ, part of the ftsQAZ operon essential for cell division.

Streptococcus pneumoniae uses quorum sensing to become competent for DNA uptake natural gene transformation.

Methods and mechanisms of quorum sensing

Figure 1. Quorum-Sensing Circuit of the Bacterial Pathogen Vibrio cholerae Red arrows indicate phosphoryl-group transfer [1]. (Figure: Matthew B. Neiditch, Princeton University, Princeton, New Jersey, United States). Cooperation among Microorganisms Ned S. Wingreen, Simon A. Levin PLoS Biol 4(9): e299. DOI:10.1371/journal.pbio.0040299 Published: September 12, 2006

Bacteria that use quorum sensing produce and secrete certain signaling compounds (called autoinducers or pheromones), one example of which are N-acyl homoserine lactones (AHL). These bacteria also have a receptor that can specifically detect the AHL (inducer). When the inducer binds the receptor, it activates transcription of certain genes, including those for inducer synthesis. There is a low likelihood of a bacterium detecting its own secreted AHL.

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 to almost zero, so the bacteria produce little inducer. With many bacteria of the same kind, the concentration of the inducer passes a threshold, whereupon more inducer is synthesised. This forms a positive feedback loop, and the receptor becomes fully activated. This induces the up regulation of other specific genes, such as luciferase in V. fishcheri. This is useful since a single V. fischeri bacterium that is luminescent would have no evolutionary advantage and would be wasting energy.

In Escherichia coli, AI-2 is produced by the lsr operon, encoding an ABC transporter which imports AI-2 into the cells during the early stationary (latent) phase of growth. AI-2 is then phosphorylated by lsrK and the newly produced phospho-AI-2 can either be internalized or used to suppress lsrR, an inhibitor of the lsr operon (thereby activating the operon). The lsr operon is also thought to be inhibited by dihydroxyacetone phosphate (DHAP) through its competitive binding to lsrR. Glyceraldehyde 3-phosphate has also been shown to inhibit the lsr operon through cAMP-CAPK-mediated inhibition. This explains why when grown with glucose E. coli will lose the ability to internalize AI-2 (because of catabolite repression). When grown normally, AI-2 presence is transient.

A first X-ray structure of a receptor (LuxP) was discovered in Vibrio harveyi in 2002, together with its inducer (AI-2), which is one of the few biomolecules containing boron (Nature 415, 545ff PDF). Autoinducer-2 is conserved among many bacterial species, including Escherichia coli, an enteric bacterium and model organism for Gram negative bacteria. Autoinducer-2 appears to be used for interspecies communication because of this conservation.

References

Further reading

• Banin, E., M. L. Vasil, and E. P. Greenberg (2005). Iron and Pseudomonas aeruginosa biofilm formation. Proc Natl Acad Sci U S A 102: 11076-81.
• Bassler BL (2006). Cell-to-cell communication in bacteria: a chemical discourse. Harvey Lect. 2004-2005 100: 123-142.
• Bassler BL and Losick R (2006). Bacterially speaking. Cell 125: 237-246.
• Camilli A and Bassler BL (2006). Bacterial small-molecule signaling pathways. Science 311: 1113-1116.

• Kolter, R. and E. P. Greenberg (2006). Microbial sciences: the superficial life of microbes. Nature 441: 300-2.

• Waters CM and Bassler BL (2005). Quorum sensing: cell-to-cell communication in bacteria. Annu Rev Cell Dev Biol 21: 319-346.

• Waters CM, Bassler BL (2006). The Vibrio harveyi quorum-sensing system uses shared regulatory components to discriminate between multiple autoinducers. Genes Dev 20: 2754-2767.

• Xavier KB and Bassler BL (2005). Regulation of uptake and processing of the quorum-sensing autoinducer AI-2 in Escherichia coli. J Bacteriol 187: 238-248.

• Xavier KB and Bassler BL (2005). Interference with AI-2-mediated bacterial cell-cell communication. Nature 437: 750-753.

External links

• The Quorum Sensing Website
• Bacterial quorum sensing in pathogenic relationships. (Infect. Immunol. 68: 4839-4849) Free Full Text 2000
• Cell-to-Cell Communication in Bacteria
• Department of Molecular Biology, Princeton University.