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REVIEW ARTICLE
Year : 2016  |  Volume : 6  |  Issue : 2  |  Page : 93-96

Quorum sensing: Bacterial chit chat


1 Department of Periodontology, Guru Nanak Dev Dental College and Research Institute, Sunam, Punjab, India
2 Dasmesh Institute of Research and Dental Sciences, Faridkot, Punjab, India

Date of Web Publication3-May-2016

Correspondence Address:
Nazia Chopra
Department of Periodontology, Guru Nanak Dev Dental College and Research Institute, Sunam, Punjab
India
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DOI: 10.4103/2249-9725.181685

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  Abstract 

The oral cavity is similar to an ecosystem that is populated by physiologically distinct microorganisms which successfully live together and thrive by continually adapting and coordinately responding to other organisms in their local environment, to nutrient flux, and to other environmental stresses. For survival, oral organisms may express sophisticated intraspecies and/or interspecies communication mechanisms that facilitate a coordinated response by members of the microbial community to environmental flux. This review paper details the bacterial communicating signaling pathways, the impact that they have on regulating gene expression and its applied aspects.

Keywords: Bacterial communication, bacterial ecology, bacterial signaling, gene expression, quorum sensing


How to cite this article:
Chopra N, Abrol S. Quorum sensing: Bacterial chit chat. Univ Res J Dent 2016;6:93-6

How to cite this URL:
Chopra N, Abrol S. Quorum sensing: Bacterial chit chat. Univ Res J Dent [serial online] 2016 [cited 2017 Jun 25];6:93-6. Available from: http://www.urjd.org/text.asp?2016/6/2/93/181685


  Introduction Top


Quorum sensing (QS) is a biological process by which bacteria are able to communicate through recognition of signaling molecules which modulate the expression of genes involved in processes related to survival, biofilm formation, virulence, and pathogenicity.[1],[2] In other words, QS is the bacterial communication phenomenon which is a process that allows bacteria to communicate using secreted chemical signaling molecules called autoinducers.[3] QS is mediated by small diffusible molecules termed autoinducers that are synthesized intracellularly and released into the surrounding milieu. As the number of cells in a bacterial colony increases, so does the extracellular concentration of the autoinducer. Once a threshold concentration is reached (at which point the population is considered to be “quorate”), productive binding of the autoinducer to cognate receptors within the bacterial cells occurs, triggering a signal transduction cascade that results in population-wide changes in gene expression.[4]

This process enables a population of bacteria to collectively regulate gene expression and, therefore, the behavior. In QS, bacteria are somewhat aware of their population density, by detecting the concentration of a particular autoinducer, which is correlated with cell density.[2],[3] This cense enables the group to express specific genes only at particular population densities. The discovery of species-specific as well as universal intracellular signaling molecules reveals that bacteria interact with one another using surprisingly sophisticated mechanisms of communications. QS enables the control of bacterial functions or processes that are unproductive when undertaken by an individual bacterium but becomes effective when undertaken by the group.[4]

Greenberg termed QS based on the coordinate behavior of a minimal unit of microorganisms. QS enhances efficacy while maintaining specificity.[1],[2],[3] This phenomenon might be the foundation upon which the more sophisticated intracellular communication is found in higher-order organisms that have evolved.

QS was originally discovered in the luminescent bacterium Vibrio fischeri. These bacteria exist as free-living cells or as symbionts in the light-producing organ of an animal host, such as the Hawaiian bobtail squid. The host provides a nutrient-rich environment for the bacterium, and the bacterium provides light for the host. It was observed that liquid cultures of V. fischeri produced light only when a large number of bacteria were present.[4],[5],[6] The initial explanation for this was that the culture medium contained an inhibitor of luminescence, which was removed when large numbers of bacteria were present. However, it was later shown that this was not the case. When a V. fischeri cell is alone, the autoinducer acyl homoserine lactone (3-oxo-C6-HSL, an acylhomoserine lactone [AHL]) is at a low concentration. At high cell concentrations, the level of the autoinducer becomes sufficient to induce transcription of the genes that produce the enzyme luciferase, leading to bioluminescence.[6] On reflection, this system is clearly a sensible one. A single cell is not capable of producing enough luciferase to cause visible luminescence. Trying to do so would be a waste of valuable resources. The sensory mechanism that produced and responded to the signal was found to consist of only two proteins, which were designated as LuxI and LuxR. Using QS, the cell can save its effort for the time when sufficient similar cells are around so that their combined action produces a visible glow. The bacteria thus behave differently in the free-living and symbiotic states.[7],[8]

Another luminescent bacterium, Vibrio harveyi, produces two autoinducers. The first (autoinducer-1 [AI-1]) is an AHL used for communication only among V. harveyi bacteria. The other AI-2 is synthesized from S-adenosyl methionine. The enzyme which catalyzes the final step in this synthesis is called LuxS. The gene for LuxS is found in many different bacteria, all of which make and respond to AI-2. This suggests that perhaps AI-2 allows bacteria to sense and react not only to members of their own species, but also to all other species that produce AI-2.[7],[8] There are two kinds of QS: Species-specific and interspecies. Species-specific QS in Gram-negative bacteria (GNB) is mediated by AHLs with various moieties distinguishing signals among species. In Gram-positive bacteria (GPB), species-specific QS is mostly facilitated through small peptides. More recently discovered interspecies communication has been linked to AI-2, a furanosyl borate diester.[7],[8]

QS system can be divided into two paradigmatic classes LuxI/LuxR type QS system in GNB and oligopeptide/two-component type QS system in GPB.[9],[10] In GNB LuxI-like proteins are the enzymes responsible for producing specific acyl homoserine lactone autoinducer. Each species of GNB produces a unique AHL or unique combination of AHLs. As a result, only members of the same species recognized and responded to it. AHL detection and subsequent alteration of downstream gene expression are mediated by cognate LuxR protein.[1],[2] Following LuxI-diverted AHL synthesis, the autoinducer freely diffuse into and out of the cell. Thus, the external AHL concentration is equivalent to the internal AHL concentration, and it increases proportionally with an increase in cell density. Once a threshold of AHL concentration is achieved, the autoinducer can be bound by its cytoplasmic counterpart, the LuxR protein. Upon interaction with a cognate AHL, a LuxR-type protein binds specific DNA promoter elements and activates downstream target gene transcription. AHL-LuxR interaction is remarkably specific and thus appears to be extremely limited cross talk in a mixed population of bacteria that use AHL-LuxR-mediated cell communication.[3],[5],[6]

In stark contrast to GNB, GPB have never been to shown to AHL-mediated QS. Instead, GPB make and transport oligopeptide autoinducer in their environment. These oligopeptides are also known as auto inducing peptides (AIPs). In further contrast to AHL signaling, the bacterial cell membrane is not permeable to AIPs, necessitating dedicate cell surface oligopeptide transporter to facilitate AIP secretion into extracellular environment.[6],[7],[8] Detection of AIP is mediated by two-component sensory transduction system. This circuit is responsible for detecting fluctuation in the vast assortment of the extracellular clues and transducing that sensory information into the cells to appropriately modulate gene expression in response to a changing environment. All bacteria of a two-component systems function by a conserved phosphorylation cascade involving a sensor kinase and response regulator pair. AIPs are the ligand for the two-component sensor kinase, and phosphorylation cascade relay information about the population density of the cell.[9],[10]


  Application of Quorum Sensing Top


Pathogen management

Quorum quenching can be regarded as all mechanisms that prevent the correct operation of QS. Autoinducer antagonists, autoinducer destroying enzymes, and other mechanisms for consuming autoinducers are known to enable “quorum quenching.” The observation that QS is linked to virulence factor production and biofilm formation suggests that many virulent Gram-negative organisms could potentially be rendered nonpathogenic by inhibition of their QS systems. This demonstrates that the species have developed strategies to interfere with QS, since QS controls the fundamental processes involved in both bacterial physiology and virulence. Researches into QS, and inhibition thereof, may provide a means of treating many common and damaging chronic infections without the use of growth-inhibitory agents, such as antibiotics, preservatives, and disinfectants.[10],[11] Existing antibiotics generally inhibit bacterial cellular processes that are essential for microbial survival, thus stimulating bacterial evolution by creating a selective pressure for drug-resistant mutations. Although QS systems are used by many bacterial pathogens to regulate virulence, they are not essential for survival. Thus, disruption of QS should attenuate pathogenicity without imposing the level of selective pressure associated with antibacterial treatments. QS-inhibitory compounds might constitute a new generation of antimicrobial agents with applications in many fields, including medicine (human and veterinary), agriculture, and aquaculture, and the associated commercial interests are substantial. Indeed, in recent years, a number of biotechnology companies that aim specifically at developing anti-QS and anti-biofilm drugs have emerged.

Several strategies aiming at the interruption of bacterial QS circuits are possible, including:[11],[12],[13] (a) inhibition of AHL signal generation, (b) inhibition of AHL signal dissemination, and (c) inhibition of AHL signal reception.

Current natural and synthetic inhibitors belong to a class of secondary metabolites termed “furanones” which contain a furan ring substituted with an acyl side chain at C3 and a bromine at C4 and other halogenated substitutions at other sites. These chemicals are structurally similar to AHL and bind to LuxR-type receptors, but fail to activate them. This includes the observations that furanones [14],[15],[16],[17] (a) repress AHL-dependent expression of V. fischeri bioluminescence; (b) inhibit AHL-controlled virulence factor production and pathogenesis in Pseudomonas aeruginosa; (c) inhibit QS-controlled luminescence and virulence of the black tiger prawn pathogen V. harveyi; and, finally, (d) inhibit QS -controlled virulence of Erwinia carotovora.

Recombinant gene expression

Perhaps some of the most exciting areas of investigation in QS is the synthesis of recombinant gene products and metabolic engineering. QS has been used to regulate gene expression and control cellular growth.[2]


  Measuring Quorum Sensing Top


Bassler et al. developed one of the most commonly used technique for measuring QS or, more specifically, bacterial autoinduction is based on the bioluminescent response of V. harveyi.[18] In this method, a cell-free conditioned medium from a culture of interest is incubated with a culture of V. harveyi and the bioluminescent response is recorded. There is an inherent error in relying on an indicator organism for sensing culture conditions, but the reactive nature of species such as AI-2 makes direct assessment challenging.

A liquid chromatography-based concentration and separation method with mass spectrometer determination of various AHLs in bacterial culture is investigated by Frommberger et al.[19] A colorimetric method for determining salicylic acid carboxyl methyltransferase (SAMT) activity has been reported.[20] In this assay, SAMT converts S-adenosylmethionine into S-adenosylhomocysteine, which is converted sequentially into homocysteine by nucleosidase, and LuxS in vitro. Furthermore, a method for measuring bacterial proteins expressed during pathogenic infection was used to isolate infection-phase-specific proteins from Vibrio cholerae. Sera from patients infected with V. cholerae were adsorbed against in vitro V. cholerae and probed with a genomic expression library of  Escherichia More Details coli constructed from a variant of the infecting strain.[21] The researchers detected the quorum-related protein LuxP among others.

Polymerase chain reaction (PCR) techniques have greatly simplified quorum data gathering and differentiation between pathogenic and nonpathogenic strains of bacteria. Hernández and Olmos [22] used PCR probes and the random amplified polymorphic DNA method for distinguishing V. harveyi pathogenic to shrimp.[22] The researchers were able to positively identify V. harveyi by the QS transcript luxN by building a consensus quorum gene cassette consisting of an AIP, a receptor kinase, and a response regulator. Nakayama et al. PCR-amplified QS regions from Enterococcus, Clostridium, and Lactobacillus species.[23] In another PCR-based method, P. aeruginosa mutants were screened for infectivity in a rat model using signature-tagged mutagenesis (STM) and high-throughput screening.[24]


  Conclusion Top


It can be well said that QS is an important process in bacterial virulence, development of therapeutic agents which can inhibit QS may offer an alternative to antibiotic-mediated bactericidal or bacteriostatic approaches and reduce the risk for development of antibiotic resistance.

Financial support and sponsorship

Department of Periodontology, Guru Nanak Dev Dental College and Research Institute, Sunam, Punjab, India.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

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Greenberg EP. Bacterial communication and group behavior. J Clin Invest 2003;112:1288-90.  Back to cited text no. 1
    
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Manefield M, de Nys R, Kumar N, Read R, Givskov M, Steinberg P, et al. Evidence that halogenated furanones from Delisea pulchra inhibit acylated homoserine lactone (AHL)-mediated gene expression by displacing the AHL signal from its receptor protein. Microbiology 1999;145 (Pt 2):283-91.  Back to cited text no. 14
    
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Manefield M, Harris L, Rice SA, de Nys R, Kjelleberg S. Inhibition of luminescence and virulence in the black tiger prawn (Penaeus monodon) pathogen Vibrio harveyi by intercellular signal antagonists. Appl Environ Microbiol 2000;66:2079-84.  Back to cited text no. 16
    
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Manefield M, Welch M, Givskov M, Salmond GP, Kjelleberg S. Halogenated furanones from the red alga, Delisea pulchra, inhibit carbapenem antibiotic synthesis and exoenzyme virulence factor production in the phytopathogen Erwinia carotovora. FEMS Microbiol Lett 2001;205:131-8.  Back to cited text no. 17
    
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Bassler BL, Wright M, Showalter RE, Silverman MR. Intercellular signalling in Vibrio harveyi: Sequence and function of genes regulating expression of luminescence. Mol Microbiol 1993;9:773-86.  Back to cited text no. 18
    
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Frommberger M, Schmitt-Kopplin P, Ping G, Frisch H, Schmid M, Zhang Y, et al. A simple and robust set-up for on-column sample preconcentration – Nano-liquid chromatography – Electrospray ionization mass spectrometry for the analysis of N-acylhomoserine lactones. Anal Bioanal Chem 2004;378:1014-20.  Back to cited text no. 19
    
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Hang L, John M, Asaduzzaman M, Bridges EA, Vanderspurt C, Kirn TJ, et al. Use of in vivo-induced antigen technology (IVIAT) to identify genes uniquely expressed during human infection with Vibrio cholerae. Proc Natl Acad Sci U S A 2003;100:8508-13.  Back to cited text no. 21
    
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Hernández G, Olmos J. Molecular identification of pathogenic and nonpathogenic strains of Vibrio harveyi using PCR and RAPD. Appl Microbiol Biotechnol 2004;63:722-7.  Back to cited text no. 22
    
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Nakayama J, Akkermans AD, De Vos WM. High-throughput PCR screening of genes for three-component regulatory system putatively involved in quorum sensing from low-G + C gram-positive bacteria. Biosci Biotechnol Biochem 2003;67:480-9.  Back to cited text no. 23
    
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