In biology, quorum sensing or quorum signaling (QS) is the process of cell-to-cell communication that allows bacteria to detect and respond to cell population density by gene regulation, typically as a means of acclimating to environmental disadvantages.
Quorum sensing is a type of cellular signaling, and can be more specifically considered a type of paracrine signaling. However, it also contains traits of autocrine signaling: a cell produces both an autoinducer molecule and the receptor for the autoinducer. As one example, quorum sensing enables bacteria to restrict the expression of specific genes to the high cell densities at which the resulting phenotypes will be most beneficial, especially for phenotypes that would be ineffective at low cell densities and therefore too energetically costly to express.
Many species of bacteria use quorum sensing to coordinate gene expression according to the density of their local population. In a similar fashion, some social insects use quorum sensing to determine where to nest. Quorum sensing in pathogenic bacteria activates host immune signaling and prolongs host survival, by limiting the bacterial intake of nutrients, such as tryptophan, which further is converted to serotonin. As such, quorum sensing allows a commensal interaction between host and pathogenic bacteria. Quorum sensing may also be useful for cancer cell communications.
In addition to its function in biological systems, quorum sensing has several useful applications for computing and robotics. In general, quorum sensing can function as a decision-making process in any decentralized system in which the components have: (a) a means of assessing the number of other components they interact with and (b) a standard response once a threshold of the number of components is detected.
Discovery The first observations of an autoinducer-controlled phenotype in bacteria were reported in 1970, by Kenneth Nealson, Terry Platt, and J. Woodland Hastings, who observed what they described as a conditioning of the medium in which they had grown the bioluminescent marine bacterium Aliivibrio fischeri. These bacteria did not synthesize luciferase—and therefore did not luminesce—in freshly inoculated culture but only after the bacterial population had increased significantly.
In a series of publications from 1998 to 2001, Bonnie Bassler showed that quorum sensing is not just an isolated mechanism in Aliivibrio fischeri, but is used ubiquitously across bacteria to communicate. This advance demonstrated that bacteria are capable of carrying out complex, collective behaviors.
Etymology Because Nealson, Platt, and Hastings attributed the conditioning of the growth medium to the growing population of cells itself, they referred to the phenomenon as autoinduction.
In 1994, after study of the phenomenon had expanded into several additional bacteria, Stephen Winans did not believe the word autoinduction fully characterized the true process so, in a review article coauthored with W. Claiborne Fuqua and E. Peter Greenberg, he introduced the term quorum sensing. Its use also avoided confusion between the terms autoinduction and autoregulation. The new term was not stumbled onto, but rather created through trial and error. Among the alternatives that Winans had created and considered were gridlockins, communiolins, and quoromones.
Bacteria
Some of the best-known examples of quorum sensing come from studies of bacteria. Bacteria use quorum sensing to regulate certain phenotype expressions, which in turn, coordinate their behaviors. Some common phenotypes include biofilm formation, virulence factor expression, and motility. Certain bacteria are able to use quorum sensing to regulate bioluminescence, nitrogen fixation and sporulation.
The quorum-sensing function is based on the local density of the bacterial population in the immediate environment. It can occur within a single bacterial species, as well as between diverse species. Both gram-positive and gram-negative bacteria use quorum sensing, but there are some major differences in their mechanisms.
Mechanism For the bacteria to use quorum sensing constitutively, they must possess three abilities: secretion of a signaling molecule, secretion of an autoinducer (to detect the change in concentration of signaling molecules), and regulation of gene transcription as a response. This process is highly dependent on the diffusion mechanism of the signaling molecules. QS signaling molecules are usually secreted at a low level by individual bacteria. At low cell density, the molecules may just diffuse away. At high cell density, the local concentration of signaling molecules may exceed its threshold level, and trigger changes in gene expression.
Gram-positive bacteria Gram-positive bacteria use autoinducing peptides (AIP) as their autoinducers.
When gram-positive bacteria detect high concentration of AIPs in their environment, that happens by way of AIPs binding to a receptor to activate a kinase. The kinase phosphorylates a transcription factor, which regulates gene transcription. This is called a two-component system.
Another possible mechanism is that AIP is transported into the cytosol, and binds directly to a transcription factor to initiate or inhibit transcription.
Gram-negative bacteria Gram-negative bacteria produce N-acyl homoserine lactones (AHL) as their signaling molecule. Usually AHLs do not need additional processing, and bind directly to transcription factors to regulate gene expression.
Some gram-negative bacteria may use two-component systems as well.
Examples
Aliivibrio fischeri The bioluminescent bacterium Aliivibrio fischeri is the first organism in which QS was observed. It lives as a mutualistic symbiont in the photophore (or light-producing organ) of the Hawaiian bobtail squid. When A. fischeri cells are free-living (or planktonic), the autoinducer is at low concentration, and, thus, cells do not show luminescence. However, when the population reaches the threshold in the photophore (about cells/ml), transcription of luciferase is induced, leading to bioluminescence. In A. fischeri, bioluminescence is regulated by AHLs (N-acyl-homoserine lactones) which is a product of the LuxI gene whose transcription is regulated by the LuxR activator. LuxR works only when AHLs binds to the LuxR.
Curvibacter sp. Curvibacter sp. is a gram-negative curved rod-formed bacterium which is the main colonizer of the epithelial cell surfaces of the early branching metazoan Hydra vulgaris. Sequencing the complete genome uncovered a circular chromosome (4.37 Mb), a plasmid (16.5 kb), and two operons coding each for an AHL (N-acyl-homoserine lactone) synthase (curI1 and curI2) and an AHL receptor (curR1 and curR2). Moreover, a study showed that these host associated Curvibacter bacteria produce a broad spectrum of AHL, explaining the presence of those operons. As mentioned before, AHL are the quorum sensing molecules of gram-negative bacteria, which means Curvibacter has a quorum sensing activity.
Even though their function in host-microbe interaction is largely unknown, Curvibacter quorum-sensing signals are relevant for host-microbe interactions. Indeed, due to the oxidoreductase activity of Hydra, there is a modification of AHL signalling molecules (3-oxo-homoserine lactone into 3-hydroxy-homoserine lactone) which leads to a different host-microbe interaction. On one hand, a phenotypic switch of the colonizer Curvibacter takes place. The most likely explanation is that the binding of 3-oxo-HSL and 3-hydroxy-HSL causes different conformational changes in the AHL receptors curR1 and curR2. As a result, there is a different DNA-binding motif affinity and thereby different target genes are activated. On the other hand, this switch modifies its ability to colonize the epithelial cell surfaces of Hydra vulgaris. Indeed, one explanation is that with a 3-oxo-HSL quorum-sensing signal, there is an up-regulation of flagellar assembly. Yet, flagellin, the main protein component of flagella, can act as an immunomodulator and activate the innate immune response in Hydra. Therefore, bacteria have less chance to evade the immune system and to colonize host tissues. Another explanation is that 3-hydroxy-HSL induces carbon metabolism and fatty acid degradation genes in Hydra. This allows the bacterial metabolism to adjust itself to the host growth conditions, which is essential for the colonization of the ectodermal mucus layer of Hydrae.
Enterococcus faecalis Enterococcus faecalis is an opportunistic, gram-positive bacteria that forms biofilm in glass. This process is also known as forming a biofilm in vitro. The presence of (Esp), a certain cell surface protein, aids the formation of a biofilm by E. faecalis.
The ability of E. faecalis to form biofilms contributes to its capacity to survive in extreme environments, and facilitates its involvement in persistent bacterial infection, particularly in the case of multi-drug resistant strains. Biofilm formation in E. faecalis is associated with DNA release, and such release has emerged as a fundamental aspect of biofilm formation. Conjugative plasmid DNA transfer in E. faecalis is enhanced by the release of peptide sex pheromones.
Escherichia coli In the gram-negative bacterium Escherichia coli, cell division may be partially regulated by AI-2-mediated quorum sensing. This species uses AI-2, which is produced and processed by the lsr operon. Part of it encodes an ABC transporter, which imports AI-2 into the cells during the early stationary (latent) phase of growth. AI-2 is then phosphorylated by the LsrK kinase, and the newly produced phospho-AI-2 can be either internalized or used to suppress LsrR, a repressor of the lsr operon (thereby activating the operon). Transcription of 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.
E. coli and Salmonella enterica do not produce AHL signals commonly found in other gram-negative bacteria. However, they have a receptor that detects AHLs from other bacteria and change their gene expression in accordance with the presence of other "quorate" populations of gram-negative bacteria. AHL quorum sensing regulates a wide range of genes through cell density. Other species of bacteria produce AHLs that Escherichia and Salmonella can detect. E. coli and Salmonella produce a receptor like protein (SdiA) allowing the amino acid sequence that is similar to AHL show AHLs can be found in the bovine rumen and E. coli responds to AHLs taken out of the bovine rumen. Most animals do not have AHL in their gastrointestinal tracts.
Salmonella enterica Salmonella encodes a LuxR homolog, SdiA, but does not encode an AHL synthase. SdiA detects AHLs produced by other species of bacteria including Aeromonas hydrophila, Hafnia alvei, and Yersinia enterocolitica. When AHL is detected, SdiA regulates the rck operon on the Salmonella virulence plasmid (pefI-srgD-srgA-srgB-rck-srgC) and a single gene horizontal acquisition in the chromosome srgE. Salmonella does not detect AHL when passing through the gastrointestinal tracts of several animal species, suggesting that the normal microbiota does not produce AHLs. However, SdiA does become activated when Salmonella transits through turtles colonized with Aeromonas hydrophila or mice infected with Yersinia enterocolitica. Therefore, Salmonella appears to use SdiA to detect the AHL production of other pathogens rather than the normal gut flora.
Myxococcus xanthus