quorum sensing quorum sensing in biology, quorum sensing or quorum signaling (qs) is the ability to detect and respond to cell population density by gene regulation. quorum sensing is a type of cellular signaling, and more specifically can be considered a type of paracrine signaling. however, it also contains traits of both autocrine signaling: a cell produces both the autoinducer molecule and the receptor for the autoinducer. as one example, qs 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 number of components is detected. discovery quorum sensing was first 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. because they attributed this conditioning of the medium to the growing population of cells itself, they referred to the phenomenon as autoinduction. bacteria part of a series onmicrobial and microbot movement microswimmers taxa bacterial motility run-and-tumble twitching gliding protist locomotion amoeboids taxis aerotaxis (oxygen) anemotaxis (wind) chemotaxis (chemicals) electrotaxis(electric current) gravitaxis (gravity) magnetotaxis (magnetic field) phototaxis (light) rheotaxis (fluid flow) thermotaxis (temperature) kinesis kinesis chemokinesis photokinesis microbots and particles microbotics nanorobotics nanomotors dna machine microparticle nanoparticle janus particles self-propelled particles swarm robotics biohybrids biohybrid microswimmers bacterial biohybrids protist biohybrids robotic sperm collective motion active matter bacteria collective motion collective cell migration quorum sensing swarming motility molecular motors biological motors flagellum archaellum cilium axoneme motor switch intraflagellar evolution motor proteins myosin kinesin dynein synthetic motors synthetic molecular motor molecular modelling molecular propeller molecular sensor molecular shuttle molecular tweezers related brownian motor biochip endocytosis axophilic migration cytoskeleton prokaryotic eukaryotic cytoplasmic streaming gray goo mucilage molecular biophysics molecular machine nanoengineering non-motile bacteria virophysics category quorum sensing of gram-negative cell gram-positive bacteria quorum sensing 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 behaviours. 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 the two-component system as well. aliivibrio fischeri the bioluminescent bacterium a. 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 1011 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. escherichia coli in the gram-negative bacterium escherichia coli (e. 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 stationery (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. 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. pseudomonas aeruginosa the opportunistic pathogen pseudomonas aeruginosa uses quorum sensing to coordinate the formation of biofilm, swarming motility, exopolysaccharide production, virulence, and cell aggregation. these bacteria can grow within a host without harming it until they reach a threshold concentration. then they become aggressive, developing to the point at which their numbers are sufficient to overcome the host's immune system, and form a biofilm, leading to disease within the host as the biofilm is a protective layer encasing the bacterial population. another form of gene regulation that allows the bacteria to rapidly adapt to surrounding changes is through environmental signaling. recent studies have discovered that anaerobiosis can significantly impact the major regulatory circuit of quorum sensing. this important link between quorum sensing and anaerobiosis has a significant impact on the production of virulence factors of this organism. there is hope among some humans that the therapeutic enzymatic degradation of the signaling molecules will be possible when treating illness caused by biofilms, and prevent the formation of such biofilms and possibly weaken established biofilms. disrupting the signaling process in this way is called quorum sensing inhibition. acinetobacter sp. it has recently been found that acinetobacter sp. also show quorum sensing activity. this bacterium, an emerging pathogen, produces ahls. acinetobacter sp. shows both quorum sensing and quorum quenching activity. it produces ahls and also, it can degrade the ahl molecules as well. aeromonas sp. this bacterium was previously considered a fish pathogen, but it has recently emerged as a human pathogen. aeromonas sp. have been isolated from various infected sites from patients (bile, blood, peritoneal fluid, pus, stool and urine). all isolates produced the two principal ahls, n-butanoylhomoserine lactone (c4-hsl) and n-hexanoyl homoserine lactone (c6-hsl). it has been documented that aeromonas sobria has produced c6-hsl and two additional ahls with n-acyl side chain longer than c6. yersinia the yenr and yeni proteins produced by the gammaproteobacterium yersinia enterocolitica are similar to aliivibrio fischeri luxr and luxi. yenr activates the expression of a small non-coding rna, yens. yens inhibits yeni expression and acylhomoserine lactone production. yenr/yeni/yens are involved in the control of swimming and swarming motility. molecules involved three-dimensional structures of proteins involved in quorum sensing were first published in 2001, when the crystal structures of three luxs orthologs were determined by x-ray crystallography. in 2002, the crystal structure of the receptor luxp of vibrio harveyi with its inducer ai-2 (which is one of the few biomolecules containing boron) bound to it was also determined. many bacterial species, including e. coli, an enteric bacterium and model organism for gram-negative bacteria, produce ai-2. a comparative genomic and phylogenetic analysis of 138 genomes of bacteria, archaea, and eukaryotes found that "the luxs enzyme required for ai-2 synthesis is widespread in bacteria, while the periplasmic binding protein luxp is present only in vibrio strains," leading to the conclusion that either "other organisms may use components different from the ai-2 signal transduction system of vibrio strains to sense the signal of ai-2 or they do not have such a quorum sensing system