Quorum sensing
Encyclopedia
Quorum sensing is a system of stimulus and response correlated to population density. Many species of bacteria
use quorum sensing to coordinate gene expression
according to the density of their local population. In similar fashion, some social insects use quorum sensing to determine where to nest. In addition to its function in biological systems, quorum sensing has several useful applications for computing and robotics.
Quorum sensing can function as a decision-making process in any decentralized system, as long as individual 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.
. Bacteria use quorum sensing to coordinate certain behaviors based on the local density of the bacterial population. Quorum sensing can occur within a single bacterial species
as well as between diverse species, and can regulate a host of different processes, in essence, serving as a simple communication network. A variety of different molecules can be used as signals. Common classes of signaling molecules are oligopeptides in Gram-positive bacteria, N-Acyl Homoserine Lactones (AHL) in Gram-negative bacteria, and a family of autoinducer
s known as autoinducer-2
(AI-2) in both Gram-negative and Gram-positive bacteria.
s or pheromones). These bacteria also have a receptor
that can specifically detect the signaling molecule (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 inducer. Thus, in order for gene transcription to be activated, the cell must encounter signaling molecules secreted by other cells in its environment. 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. However, as the population grows, the concentration of the inducer passes a threshold, causing more inducer to be synthesized. This forms a positive feedback
loop, and the receptor becomes fully activated. Activation of the receptor induces the up-regulation
of other specific genes, causing all of the cells to begin transcription at approximately the same time. This coordinated behavior of bacterial cells can be useful in a variety of situations. For instance, the bioluminescent luciferase
produced by V. fischeri would not be visible if it were produced by a single cell. By using quorum sensing to limit the production of luciferase to situations when cell populations are large, V. fischeri cells are able to avoid wasting energy on the production of useless product.
, a bioluminiscent bacterium that lives as a mutualistic symbiont in the photophore
(or light-producing organ) of the Hawaiian bobtail squid
. When V. fischeri cells are free-living (or plankton
ic), the autoinducer is at low concentration, and, thus, cells do not luminesce. However, when they are highly concentrated in the photophore (about cells/ml), transcription of luciferase
is induced, leading to bioluminescence
.
(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 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.
use quorum sensing to coordinate the formation of biofilm
s, swarming motility
, exopolysaccharide
production, and cell aggregation. These bacteria can grow within a host without harming it, until they reach a certain concentration. Then they become aggressive, develop to the point at which their numbers become sufficient to overcome the host's immune system
, and form a biofilm
, leading to disease
within the host. 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 QS. This important link between QS and anaerobiosis has a significant impact on production of virulence factors of this organism
. Garlic
experimentally blocks quorum sensing in Pseudomonas aeruginosa
. It is hoped that the therapeutic enzymatic degradation of the signaling molecules will prevent the formation of such biofilms and possibly weaken established biofilms. Disrupting the signalling process in this way is called quorum inhibition.
s 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 at all."
Certain bacteria can produce enzymes called lactonase
s that can target and inactivate AHLs.
system occur in the Gram-negative
Proteobacteria
. A comparison between the Proteobacteria phylogeny as generated by 16S ribosomal RNA
sequences and phylogenies of LuxI-, LuxR-, or LuxS-homologs shows a notably high level of global similarity. Overall, the quorum sensing genes seem to have diverged along with the Protecobacteria phylum as a whole. This indicates that these quorum sensing systems are quite ancient, and arose very early in the Proteobacteria lineage.
Although examples of horizontal gene transfer
are apparent in LuxI, LuxR, and LuxS phylogenies, they are relatively rare. This result is in line with the observation that quorum sensing genes tend to control the expression of a wide array of genes scattered throughout the bacterial chromosome. A recent acquisition by horizontal gene transfer would be unlikely to have integrated itself to this degree. Given that the majority of autoinducer–synthase/receptor occurs in tandem in bacterial genomes, it is also rare that they switch partners and so pairs tend to co-evolve.
The phylogeny of quorum sensing genes in Gammaproteobacteria
(which includes Pseudomonas aeruginosa
and Escherichia coli
) is especially interesting. The LuxI/LuxR genes form a functional pair, with LuxI as the auto-inducer synthase and LuxR as the receptor. Gamma Proteobacteria are unique in possessing quorum sensing genes, which, although functionally similar to the LuxI/LuxR genes, have a markedly divergent sequence. This family of quorum-sensing homologs
may have arisen in the gamma Proteobacteria ancestor, although the cause of their extreme sequence divergence yet maintenance of functional similarity has yet to be explained. In addition, species that employ multiple discrete quorum sensing systems are almost all members of the gamma Proteobacteria, and evidence of horizontal transfer of quorum sensing genes is most evident in this class.
The current state of antibiotic affairs is due to the manner in which existing antibiotics work. All current antibiotics aim to kill the individual bacteria in one manner or another (by inhibiting synthesis of new bacteria, usually). This environmental pressure activates the evolutionary mechanisms that select for resistant strains. In other words, bacteria that are not resistant to the antibiotic are killed off, leaving the resistant organisms to multiply unchecked without competition. This is why resistant strains spread so rapidly and occur so frequently.
Recent research into quorum sensing systems has produced compounds that can disrupt the bacteria's ability to communicate, thereby disabling or diminishing the bacteria's ability to become pathogenic. Therefore, the body is not compromised by cell damage, inflammation, toxicity, or other detrimental effects of the bacteria. This gives the body time to eradicate the bacteria naturally through normal immune system functions.
The advantage of the anti-quorum sensing approach to controlling infection is that there are few evolutionary forces that select for resistance—there is little in the process that would create resistant strains. Since the compounds kill none of the bacteria, any resistant mutations must compete with living, non-resistant individuals. In other words, there is no survival advantage to the resistant mutations, and natural selection does not come into play. Resistant strains will be unlikely to occur.
. The waiting period is inversely related to the quality of the site; for instance, a worker that has found a poor site will wait longer than a worker that encountered a good site. As the new recruits visit the potential nest site and make their own assessment of its quality, the number of ants visiting the crevice increases. During this stage, ants may be visiting many different potential nests. However, because of the differences in the waiting period, the number of ants in the best nest will tend to increase at the greatest rate. Eventually, the ants in this nest will sense that the rate at which they encounter other ants has exceeded a particular threshold, indicating that the quorum number has been reached. Once the ants sense a quorum, they return to the destroyed nest and begin rapidly carrying the brood, queen, and fellow workers to the new nest. Scouts that are still tandem-running to other potential sites are also recruited to the new nest, and the entire colony moves. Thus, although no single worker may have visited and compared all of the available options, quorum sensing enables the colony as a whole to quickly make good decisions about where to move.
that hangs from a branch or overhanging structure. This swarm persists during the decision-making phase until a new nest site is chosen.
The quorum sensing process in honey bees is similar to the method used by Temnothorax ants in several ways. A small portion of the workers leave the swarm to search out new nest sites, and each worker assesses the quality of the cavity it finds. The worker then returns to the swarm and recruits other workers to her cavity using the honey bee waggle dance
. However, instead of using a time delay, the number of dance repetitions the worker performs is dependent on the quality of the site. Workers that found poor nests stop dancing sooner, and can therefore be recruited to the better sites. Once the visitors to a new site sense that a quorum number (usually 10–20 bees) has been reached, they return to the swarm and begin using a new recruitment method called piping. This vibration signal causes the swarm to take off and fly to the new nest location. In an experimental test, this decision-making process enabled honey bee swarms to choose the best nest site in four out of five trials.
Quorum sensing can also be used to coordinate the behavior of autonomous robot swarms. Using a process similar to that used by Temnothorax ants, robots can make rapid group decisions without the direction of a controller.
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
use quorum sensing to coordinate gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
according to the density of their local population. In similar fashion, some social insects use quorum sensing to determine where to nest. In addition to its function in biological systems, quorum sensing has several useful applications for computing and robotics.
Quorum sensing can function as a decision-making process in any decentralized system, as long as individual 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.
Quorum quenching
Quorum quenching may be achieved by degrading the signalling molecule. Using a KG medium, quorum quenching bacteria can be readily isolated from various environments including that which has previously been considered as unculturable. Recently, a well-studied quorum quenching bacteria has been isolated and its AHL degradation kinetic has been studied by using rapid resolution liquid chromatography (RRLC).Bacteria
Some of the best-known examples of quorum sensing come from studies of bacteriaBacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
. Bacteria use quorum sensing to coordinate certain behaviors based on the local density of the bacterial population. Quorum sensing can occur within a single bacterial species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...
as well as between diverse species, and can regulate a host of different processes, in essence, serving as a simple communication network. A variety of different molecules can be used as signals. Common classes of signaling molecules are oligopeptides in Gram-positive bacteria, N-Acyl Homoserine Lactones (AHL) in Gram-negative bacteria, and a family of autoinducer
Autoinducer
Autoinducers are chemical signaling molecules that are produced and used by bacteria participating in quorum sensing. Quorum sensing is a phenomenon that allows both Gram-negative and Gram-positive bacteria to sense one another and to regulate a wide variety of physiological activities. Such...
s known as autoinducer-2
Autoinducer-2
Autoinducer-2 , a furanosyl borate diester, is a member of a family of signaling molecules used in quorum sensing. AI-2 is unique in that it is one of only a few known biomolecules incorporating boron. First identified in the marine bacterium Vibrio harveyi, AI-2 is produced and recognized by many...
(AI-2) in both Gram-negative and Gram-positive bacteria.
Mechanism
Bacteria that use quorum sensing constantly produce and secrete certain signaling molecules (called autoinducerAutoinducer
Autoinducers are chemical signaling molecules that are produced and used by bacteria participating in quorum sensing. Quorum sensing is a phenomenon that allows both Gram-negative and Gram-positive bacteria to sense one another and to regulate a wide variety of physiological activities. Such...
s or pheromones). These bacteria also have a receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
that can specifically detect the signaling molecule (inducer
Inducer
In molecular biology, an inducer is a molecule that starts gene expression.For a gene to be expressed, its DNA sequence must be copied to make a smaller, mobile molecule called messenger RNA , which carries the instructions for making a protein to the site where the protein is manufactured...
). When the inducer binds the receptor, it activates transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
of certain genes
Gênes
Gênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...
, including those for inducer synthesis. There is a low likelihood of a bacterium detecting its own secreted inducer. Thus, in order for gene transcription to be activated, the cell must encounter signaling molecules secreted by other cells in its environment. When only a few other bacteria of the same kind are in the vicinity, diffusion
Diffusion
Molecular diffusion, often called simply diffusion, is the thermal motion of all particles at temperatures above absolute zero. The rate of this movement is a function of temperature, viscosity of the fluid and the size of the particles...
reduces the concentration of the inducer in the surrounding medium to almost zero, so the bacteria produce little inducer. However, as the population grows, the concentration of the inducer passes a threshold, causing more inducer to be synthesized. This forms a positive feedback
Positive feedback
Positive feedback is a process in which the effects of a small disturbance on a system include an increase in the magnitude of the perturbation. That is, A produces more of B which in turn produces more of A. In contrast, a system that responds to a perturbation in a way that reduces its effect is...
loop, and the receptor becomes fully activated. Activation of the receptor induces the up-regulation
Regulation
Regulation is administrative legislation that constitutes or constrains rights and allocates responsibilities. It can be distinguished from primary legislation on the one hand and judge-made law on the other...
of other specific genes, causing all of the cells to begin transcription at approximately the same time. This coordinated behavior of bacterial cells can be useful in a variety of situations. For instance, the bioluminescent luciferase
Luciferase
Luciferase is a generic term for the class of oxidative enzymes used in bioluminescence and is distinct from a photoprotein. One famous example is the firefly luciferase from the firefly Photinus pyralis. "Firefly luciferase" as a laboratory reagent usually refers to P...
produced by V. fischeri would not be visible if it were produced by a single cell. By using quorum sensing to limit the production of luciferase to situations when cell populations are large, V. fischeri cells are able to avoid wasting energy on the production of useless product.
Vibrio fischeri
Quorum sensing was first observed in Vibrio fischeriVibrio fischeri
Vibrio fischeri is a gram-negative rod-shaped bacterium found globally in marine environments. V. fischeri has bioluminescent properties, and is found predominantly in symbiosis with various marine animals, such as the bobtail squid. It is heterotrophic and moves by means of flagella. Free living...
, a bioluminiscent bacterium that lives as a mutualistic symbiont in the photophore
Photophore
A photophore is a light-emitting organ which appears as luminous spots on various marine animals, including fish and cephalopods. The organ can be simple, or as complex as the human eye; equipped with lenses, shutters, color filters and reflectors...
(or light-producing organ) of the Hawaiian bobtail squid
Hawaiian Bobtail Squid
Euprymna scolopes, also known as the Hawaiian Bobtail Squid, is a species of bobtail squid in the family Sepiolidae. It is native to the central Pacific Ocean, where it occurs in shallow coastal waters off the Hawaiian Islands and Midway Island...
. When V. fischeri cells are free-living (or plankton
Plankton
Plankton are any drifting organisms that inhabit the pelagic zone of oceans, seas, or bodies of fresh water. That is, plankton are defined by their ecological niche rather than phylogenetic or taxonomic classification...
ic), the autoinducer is at low concentration, and, thus, cells do not luminesce. However, when they are highly concentrated in the photophore (about cells/ml), transcription of luciferase
Luciferase
Luciferase is a generic term for the class of oxidative enzymes used in bioluminescence and is distinct from a photoprotein. One famous example is the firefly luciferase from the firefly Photinus pyralis. "Firefly luciferase" as a laboratory reagent usually refers to P...
is induced, leading to bioluminescence
Bioluminescence
Bioluminescence is the production and emission of light by a living organism. Its name is a hybrid word, originating from the Greek bios for "living" and the Latin lumen "light". Bioluminescence is a naturally occurring form of chemiluminescence where energy is released by a chemical reaction in...
.
Escherichia coli
In the Gram-negative bacteria Escherichia coliEscherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
(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
Operon
In genetics, an operon is a functioning unit of genomic DNA containing a cluster of genes under the control of a single regulatory signal or promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo trans-splicing to create...
. 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
Kinase
In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...
, 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
Glyceraldehyde 3-phosphate
Glyceraldehyde 3-phosphate, also known as triose phosphate or 3-phosphoglyceraldehyde and abbreviated as G3P, GADP, GAP, TP, GALP or PGAL, is a chemical compound that occurs as an intermediate in several central metabolic pathways of all organisms...
has also been shown to inhibit the lsr operon through cAMP
Cyclic adenosine monophosphate
Cyclic adenosine monophosphate is a second messenger important in many biological processes...
-CAPK-mediated inhibition. This explains why, when grown with glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
, E. coli will lose the ability to internalize AI-2 (because of catabolite repression
Catabolite repression
Carbon catabolite repression, or simply catabolite repression, is an important part of global control system of various bacteria and other micro-organisms. Catabolite repression allows bacteria to adapt quickly to a preferred carbon and energy source first...
). 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 bacteria Pseudomonas aeruginosaPseudomonas aeruginosa
Pseudomonas aeruginosa is a common bacterium that can cause disease in animals, including humans. It is found in soil, water, skin flora, and most man-made environments throughout the world. It thrives not only in normal atmospheres, but also in hypoxic atmospheres, and has, thus, colonized many...
use quorum sensing to coordinate the formation of biofilm
Biofilm
A biofilm is an aggregate of microorganisms in which cells adhere to each other on a surface. These adherent cells are frequently embedded within a self-produced matrix of extracellular polymeric substance...
s, swarming motility
Swarming motility
Swarming motility is a rapid and coordinated translocation of a bacterial population across solid or semi-solid surfaces. This type of motility is an example of an emerging concept in microbiology : bacterial multicellularity...
, exopolysaccharide
Exopolysaccharide
Exopolysaccharides are high-molecular-weight polymers that are composed of sugar residues and are secreted by a microorganism into the surrounding environment. Microorganisms synthesize a wide spectrum of multifunctional polysaccharides including intracellular polysaccharides, structural...
production, and cell aggregation. These bacteria can grow within a host without harming it, until they reach a certain concentration. Then they become aggressive, develop to the point at which their numbers become sufficient to overcome the host's immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
, and form a biofilm
Biofilm
A biofilm is an aggregate of microorganisms in which cells adhere to each other on a surface. These adherent cells are frequently embedded within a self-produced matrix of extracellular polymeric substance...
, leading to disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
within the host. Another form of gene regulation that allows the bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
to rapidly adapt to surrounding changes is through environmental signaling. Recent studies have discovered that anaerobiosis can significantly impact the major regulatory circuit of QS. This important link between QS and anaerobiosis has a significant impact on production of virulence factors of this organism
Organism
In biology, an organism is any contiguous living system . In at least some form, all organisms are capable of response to stimuli, reproduction, growth and development, and maintenance of homoeostasis as a stable whole.An organism may either be unicellular or, as in the case of humans, comprise...
. Garlic
Garlic
Allium sativum, commonly known as garlic, is a species in the onion genus, Allium. Its close relatives include the onion, shallot, leek, chive, and rakkyo. Dating back over 6,000 years, garlic is native to central Asia, and has long been a staple in the Mediterranean region, as well as a frequent...
experimentally blocks quorum sensing in Pseudomonas aeruginosa
Pseudomonas aeruginosa
Pseudomonas aeruginosa is a common bacterium that can cause disease in animals, including humans. It is found in soil, water, skin flora, and most man-made environments throughout the world. It thrives not only in normal atmospheres, but also in hypoxic atmospheres, and has, thus, colonized many...
. It is hoped that the therapeutic enzymatic degradation of the signaling molecules will prevent the formation of such biofilms and possibly weaken established biofilms. Disrupting the signalling process in this way is called quorum inhibition.
Acinetobacter sp.
It has recently been found that Acinetobacter sp. also show quorum sensing activity. This bacterium, an emerging pathogen, produces AHLs. Interestingly, 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 used to be 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.Molecules involved in quorum sensing
Three-dimensional structures of proteins involved in quorum sensing were first published in 2001, when the crystal structureCrystal structure
In mineralogy and crystallography, crystal structure is a unique arrangement of atoms or molecules in a crystalline liquid or solid. A crystal structure is composed of a pattern, a set of atoms arranged in a particular way, and a lattice exhibiting long-range order and symmetry...
s of three LuxS orthologs were determined by X-ray crystallography
X-ray crystallography
X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...
. In 2002, the crystal structure of the receptor LuxP of Vibrio harveyi
Vibrio harveyi
Vibrio harveyi is a species of Gram-negative, bioluminescent, marine bacteria in the genus Vibrio. V. harveyi are rod-shaped, motile , facultatively anaerobic, halophilic, and competent for both fermentative and respiratory metabolism. They do not grow at 4°C or above 35°C. V...
with its inducer AI-2 (which is one of the few biomolecules containing boron
Boron
Boron is the chemical element with atomic number 5 and the chemical symbol B. Boron is a metalloid. Because boron is not produced by stellar nucleosynthesis, it is a low-abundance element in both the solar system and the Earth's crust. However, boron is concentrated on Earth by the...
) 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
Periplasmic space
The periplasmic space or periplasm is a space between the peptidoglycan cell wall and inner membrane of Gram-negative bacteria or the equivalent space outside the inner membrane of Gram-positive bacteria. It may constitute up to 40% of the total cell volume in Gram-negative species, and is...
binding protein
Binding protein
A binding protein is any protein that acts as an agent to bind two or more molecules together.Examples include:*DNA-binding protein**Single-strand binding protein**Telomere-binding protein*RNA-binding protein**Poly-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 at all."
Certain bacteria can produce enzymes called lactonase
Lactonase
Lactonase is a metalloenzyme, produced by certain species of bacteria, which targets and inactivates acylated homoserine lactones ....
s that can target and inactivate AHLs.
Sequence analysis
The majority of quorum sensing systems that fall under the "two-gene" (an autoinducer synthase coupled with a receptor molecule) paradigm as defined by the Vibrio fischeriVibrio fischeri
Vibrio fischeri is a gram-negative rod-shaped bacterium found globally in marine environments. V. fischeri has bioluminescent properties, and is found predominantly in symbiosis with various marine animals, such as the bobtail squid. It is heterotrophic and moves by means of flagella. Free living...
system occur in the Gram-negative
Gram-negative
Gram-negative bacteria are bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color...
Proteobacteria
Proteobacteria
The Proteobacteria are a major group of bacteria. They include a wide variety of pathogens, such as Escherichia, Salmonella, Vibrio, Helicobacter, and many other notable genera....
. A comparison between the Proteobacteria phylogeny as generated by 16S ribosomal RNA
16S ribosomal RNA
16S ribosomal RNA is a component of the 30S subunit of prokaryotic ribosomes. It is approximately 1.5kb in length...
sequences and phylogenies of LuxI-, LuxR-, or LuxS-homologs shows a notably high level of global similarity. Overall, the quorum sensing genes seem to have diverged along with the Protecobacteria phylum as a whole. This indicates that these quorum sensing systems are quite ancient, and arose very early in the Proteobacteria lineage.
Although examples of horizontal gene transfer
Horizontal gene transfer
Horizontal gene transfer , also lateral gene transfer , is any process in which an organism incorporates genetic material from another organism without being the offspring of that organism...
are apparent in LuxI, LuxR, and LuxS phylogenies, they are relatively rare. This result is in line with the observation that quorum sensing genes tend to control the expression of a wide array of genes scattered throughout the bacterial chromosome. A recent acquisition by horizontal gene transfer would be unlikely to have integrated itself to this degree. Given that the majority of autoinducer–synthase/receptor occurs in tandem in bacterial genomes, it is also rare that they switch partners and so pairs tend to co-evolve.
The phylogeny of quorum sensing genes in Gammaproteobacteria
Gammaproteobacteria
Gammaproteobacteria is a class of several medically, ecologically and scientifically important groups of bacteria, such as the Enterobacteriaceae , Vibrionaceae and Pseudomonadaceae. An exceeding number of important pathogens belongs to this class, e.g...
(which includes Pseudomonas aeruginosa
Pseudomonas aeruginosa
Pseudomonas aeruginosa is a common bacterium that can cause disease in animals, including humans. It is found in soil, water, skin flora, and most man-made environments throughout the world. It thrives not only in normal atmospheres, but also in hypoxic atmospheres, and has, thus, colonized many...
and Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
) is especially interesting. The LuxI/LuxR genes form a functional pair, with LuxI as the auto-inducer synthase and LuxR as the receptor. Gamma Proteobacteria are unique in possessing quorum sensing genes, which, although functionally similar to the LuxI/LuxR genes, have a markedly divergent sequence. This family of quorum-sensing homologs
Homology (biology)
Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...
may have arisen in the gamma Proteobacteria ancestor, although the cause of their extreme sequence divergence yet maintenance of functional similarity has yet to be explained. In addition, species that employ multiple discrete quorum sensing systems are almost all members of the gamma Proteobacteria, and evidence of horizontal transfer of quorum sensing genes is most evident in this class.
Controversy
As quorum sensing implies a cooperative behavior, this concept has been challenged by the evolutionary implication of cooperative cheaters. This is circumvented by the concept of diffusion sensing, which has been an alternative and complementary model to quorum sensing. However, both explanations face the problems of signalling in either complex (multiple species sharing the same space) or simple (one single cell confined to a limited volume) environments where the spatial distribution of the cells can be more important for sensing than the cell population density. A new model, efficiency sensing, which takes into account both problematics, population density and spatial confinement, has been proposed as an alternative. One of the probable reasons for controversy is that current terminologies (quorum sensing, diffusion sensing, efficiency sensing) all imply an understanding of the motives and benefits of the process, and may be observed to apply under some circumstances but not others. Perhaps a sensible resolution to these controversies could be to return the terminology of the process to autoinduction, as originally described by Hastings and coworkers, as this term does not imply understanding of the intent(s) or benefit(s) of the process.Anti-quorum sensing medical treatments
Today, about 70% of the bacteria that cause infections are resistant to at least one of the drugs most commonly used for treatment. Some organisms are resistant to all approved antibiotics and can be treated only with experimental and potentially toxic drugs. A substantial increase in resistance of bacteria that cause community-acquired infections has also been documented, especially in the staphylococci and pneumococci, which are prevalent causes of disease and mortality. In a recent study, 25% of bacterial pneumonia cases were shown to be resistant to penicillin, and an additional 25% of cases were resistant to more than one antibiotic.The current state of antibiotic affairs is due to the manner in which existing antibiotics work. All current antibiotics aim to kill the individual bacteria in one manner or another (by inhibiting synthesis of new bacteria, usually). This environmental pressure activates the evolutionary mechanisms that select for resistant strains. In other words, bacteria that are not resistant to the antibiotic are killed off, leaving the resistant organisms to multiply unchecked without competition. This is why resistant strains spread so rapidly and occur so frequently.
Recent research into quorum sensing systems has produced compounds that can disrupt the bacteria's ability to communicate, thereby disabling or diminishing the bacteria's ability to become pathogenic. Therefore, the body is not compromised by cell damage, inflammation, toxicity, or other detrimental effects of the bacteria. This gives the body time to eradicate the bacteria naturally through normal immune system functions.
The advantage of the anti-quorum sensing approach to controlling infection is that there are few evolutionary forces that select for resistance—there is little in the process that would create resistant strains. Since the compounds kill none of the bacteria, any resistant mutations must compete with living, non-resistant individuals. In other words, there is no survival advantage to the resistant mutations, and natural selection does not come into play. Resistant strains will be unlikely to occur.
Social insects
Social insect colonies are an excellent example of a decentralized system, because no individual is in charge of directing or making decisions for the colony. Several groups of social insects have been shown to use quorum sensing in a process that resembles collective decision-making.Ants
Colonies of the ant Temnothorax albipennis nest in small crevices between rocks. When the rocks shift and the nest is broken open, these ants must quickly choose a new nest to move into. During the first phase of the decision-making process, a small portion of the workers leave the destroyed nest and search for new crevices. When one of these scout ants finds a potential nest, she assesses the quality of the crevice based on a variety of factors including the size of the interior, the number of openings (based on light level), and the presence or absence of dead ants. The worker then returns to the destroyed nest, where it will wait for a short period before recruiting other workers to follow her to the nest she found, using a process called tandem runningTandem running
Tandem running is a method of recruitment used by some species of ants, such as Temnothorax albipennis, to lead nestmates to food. It is dissimilar to other recruitment strategies used by social insects such as pheromone trails, in that ants using tandem running can recruit only one worker at a time...
. The waiting period is inversely related to the quality of the site; for instance, a worker that has found a poor site will wait longer than a worker that encountered a good site. As the new recruits visit the potential nest site and make their own assessment of its quality, the number of ants visiting the crevice increases. During this stage, ants may be visiting many different potential nests. However, because of the differences in the waiting period, the number of ants in the best nest will tend to increase at the greatest rate. Eventually, the ants in this nest will sense that the rate at which they encounter other ants has exceeded a particular threshold, indicating that the quorum number has been reached. Once the ants sense a quorum, they return to the destroyed nest and begin rapidly carrying the brood, queen, and fellow workers to the new nest. Scouts that are still tandem-running to other potential sites are also recruited to the new nest, and the entire colony moves. Thus, although no single worker may have visited and compared all of the available options, quorum sensing enables the colony as a whole to quickly make good decisions about where to move.
Honey bees
Honey bees (Apis mellifera) also use quorum sensing to make decisions about new nest sites. Large colonies reproduce through a process called budding, in which the queen leaves the hive with a portion of the workers to form a new nest elsewhere. After leaving the nest, the workers form a swarmSwarming (honeybee)
Swarming is the natural means of reproduction of honey bee colonies. A new honey bee colony is formed when the queen bee leaves the colony with a large group of worker bees, a process called swarming. In the prime swarm, about 60% of the worker bees leave the original hive location with the old...
that hangs from a branch or overhanging structure. This swarm persists during the decision-making phase until a new nest site is chosen.
The quorum sensing process in honey bees is similar to the method used by Temnothorax ants in several ways. A small portion of the workers leave the swarm to search out new nest sites, and each worker assesses the quality of the cavity it finds. The worker then returns to the swarm and recruits other workers to her cavity using the honey bee waggle dance
Waggle dance
Waggle dance is a term used in beekeeping and ethology for a particular figure-eight dance of the honey bee. By performing this dance, successful foragers can share with their hive mates information about the direction and distance to patches of flowers yielding nectar and pollen, to water...
. However, instead of using a time delay, the number of dance repetitions the worker performs is dependent on the quality of the site. Workers that found poor nests stop dancing sooner, and can therefore be recruited to the better sites. Once the visitors to a new site sense that a quorum number (usually 10–20 bees) has been reached, they return to the swarm and begin using a new recruitment method called piping. This vibration signal causes the swarm to take off and fly to the new nest location. In an experimental test, this decision-making process enabled honey bee swarms to choose the best nest site in four out of five trials.
Computing and robotics
Quorum sensing can be a useful tool for improving the function of self-organizing networks such as the SECOAS (Self-Organizing Collegiate Sensor) environmental monitoring system. In this system, individual nodes sense that there is a population of other nodes with similar data to report. The population then nominates just one node to report the data, resulting in power savings. Ad-hoc wireless networks can also benefit from quorum sensing, by allowing the system to detect and respond to network conditions.Quorum sensing can also be used to coordinate the behavior of autonomous robot swarms. Using a process similar to that used by Temnothorax ants, robots can make rapid group decisions without the direction of a controller.
External links
- The Quorum Sensing Website
- Cell-to-Cell Communication in Bacteria
- The SECOAS project—Development of a Self-Organising, Wireless Sensor Network for Environmental Monitoring
- Measurement of Space: From Ants to Robots
- Instant insight into quorum sensing from the Royal Society of ChemistryRoyal Society of ChemistryThe Royal Society of Chemistry is a learned society in the United Kingdom with the goal of "advancing the chemical sciences." It was formed in 1980 from the merger of the Chemical Society, the Royal Institute of Chemistry, the Faraday Society and the Society for Analytical Chemistry with a new...
- Bonnie Bassler: Discovering bacteria's amazing communication system
- "Cell-Cell Communication in Bacteria" (Quorum sensing) by Bonnie Bassler (Princeton)