COVID-19 Update - This is to inform you that the Government of India has announced a complete lockdown in India 22nd March 2020 to 14th April 2020. As a result, our offices will now be closed till 14th April 2020 and all our employees will be working from home. Office telephones will not be answered, and therefore you are requested to direct all your queries related to manuscript submission, review process, publication etc. at below mentioned details.,, Mob. 8826373757, 8826859373, 9910947804

Print ISSN:-2581-9836

Online ISSN:-2457-0087

Current Issue

Year 2020

Volume: 5 , Issue: 1

  • Article highlights
  • Article tables
  • Article images

Article view: 130

Article download: 96

Sangeetha S, Padmalochani B, Kshirsagar, Kothimbakkam, and Kumari C: Quorum sensing — Polymicrobial challenge in periodontics


Periodontal disease is an inflammatory disease which is multifactorial in origin causing destruction of the periodontium and also acts as a risk factor for systemic diseases such as cardiovascular diseases, endocrine disorders, hemorrhagic disorders, renal diseases, liver diseases, pulmonary diseases, and pre-term low birth weight infants.1 Throughout life, body interface surfaces are exposed to microbial colonization resulting in establishment of microbiota lives in harmony with the host. As teeth provide hard, non-shedding surfaces there is a development of extensive bacterial deposits. The accumulation and metabolism induced growth of bacteria on tooth surfaces is the influencing factor for initiation of gingivitis and periodontitis.

On mechanical cleaning of teeth, hydrophobic macromolecules begin to adsorb to the tooth surface forming conditioning film known as acquired pellicle which consists of various salivary glycoproteins and antibodies. This results in alteration of the surface free energy which increases the efficiency of bacterial adhesion. Bacteria adhere to these coated surfaces leading to formation of a biofilm. In 1mm2 of dental plaque weighing approximately 1 mg contains 200 million bacteria.

Plaque Formation

Approximately 700 species of microorganisms colonize the human oral cavity which includes commensals and sparse population of pathogenic bacteria. Primary colonization of bacteria occurs by adsorbing on to the pellicle coated surface. Facultative anaerobic gram – positive cocci dominate. At 24 hours plaque mainly shows streptococci, of which Streptococcus sanguis is predominant. Streptococci and other precursor organisms provide unique receptor sites for later, more pathogenic colonizers such as Fusobacterium nucleatum which acts as bridging bacteria, Tannerella forsythia, Treponema denticola, and Porphyromonas gingivalis.3 which are closely associated with the development of periodontitis.2

F. nucleatum, P.intermedia, and P. gingivalis are the three very important microorganisms in the development of periodontal disease. Fusobacterium nucleatum plays an important role in the subgingival microbiota. It has ability to coaggregate with most of the microorganisms in plaque and with periodontal pathogens. P.intermedia is elevated in acute necrotizing ulcerative gingivitis. P. gingivalis plays an important role in bone and tissue destruction.

Micro-organisms are mostly organized in communities and they assemble on substrates known as biofilm. A typical biofilm forms at the interface and comprises of microbial cells enclosed within a matrix consisting of polysaccharides, proteins, nucleic acid and lipids, derived from microbial and environmental sources.4 Plaque biofilm is the etiologic factor for periodontitis. This biofilm is stabilized by extracellular DNA (eDNA).5 In addition, this eDNA may be a source for potential transfer of antibiotic resistance or virulence genes between species within the communities.6 The creation of bio-films is regulated by signaling process called quorum sensing.

Quorum Sensing

Quorum is a Latin word. Bacteria produce chemical signals and other bacteria can respond to them by a mechanism through which they communicate population behavior and phenotype known as cell-cell communication or cell-cell Signaling or quorum sensing.7,8 As communication is the resolving factor to interpret discrepancies, biofilms forming bacteria adopt specialized roles and communicate with one another.9

To initialize communication between them, Autoinducers or pheromones which are small hormone like chemical signaling molecules play an important role. In formation and maturation of plaque. It either diffuses freely across the cell membranes or is actively transported out of the cell.10 Autoinducer 2 is described as a global signal molecule for interspecies communication, as it is made by gram-positive as well as gram-negative bacteria.10 When the population of Quorum Sensing producing bacteria leaps, the individual organisms engenders and secrete the autoinducers into the extracellular environment. Thus, the concentration of external autoinducer is congruent with cell population density. By monitoring the extracellular autoinducer concentration, the bacteria can count one another and alter target gene expression.11 Though planktonic cells secrete chemical signals at low concentration, there is no change in genetic expression. When Biofilm cells held together in dense populations, the secreted chemical signals attain at higher concentrations. These molecules then re-cross the cell membranes and trigger changes in genetic activity leading to the production of various products which increase bacterial pathogenicity9 (Table 1).

Table 1
Acylated hemoserine lactone Gram negative and Intraspecies
Peptides Gram positive and Intraspecies
Furanosyl borate diester Gram positive and gram negative, Interspecies


Table 2
Garlic Ajoene, Disulphides, Trisulphides 15
Turmeric Curcumin 15
Citrus flavonoids Flavonine naringenin 15
Horseradish Iberin 15
Red Marine Alage(Dalea Pulchra) Halogenated Furanones 14
Grape Fruit Extract Furocoumarins, Carotenoids, Limonoids, Pectin 14
Clove Extract Eugenol, Hexane, Menthol 12
Coffee Extract Caffeine 13

Quoru m Quenching compounds in plants

Figure 1

Biofilm formation

Figure 2

Action of autoinducers

At this instance, bacteria produce a light inducing property to attract one another to increase dense population known as bioluminescence. The bacterial signaling was first described in the bioluminescent marine organism Vibrio fischeri [Nealson and Hastings, 1979 where a diffusible signal N-acyl homoserine lactone (AHL) was responsible for the induction of bioluminescence.16 In the light organ of the Hawaiian squid Euprymnascolopes, V. fischeri colonizes and induce the expression of genes required for bioluminescence. This bioluminescence increases the density of microorganism present in a particular area and makes cell to cell communication effective. When they are at high cell concentrations, the level of the autoinducer becomes adequate to induce transcription of the genes that produce the enzyme luciferase.16 This enzyme causes the oxidation of the reduced flavin mononucleotide to produce a long-chain fatty acid, water and flavin mononucleotide. This reaction causes the emission of blue-green light along with the oxidation reaction and therefore is termed as bioluminescence. Different luminescent bacteria may show different luminescence spectrum and colour of the emitted light due to the shift in wavelength caused because of the sensitizer proteins.17

Quorum Sensing is believed to regulate and control the traits of micro-organism such as competence development, sporulation, Antibiotic resistence, virulence factor, induction, Cell differentiation and nutrient flux along with other physiological events in pathogenic bacterial infections.18,11

Finally, when the threshold concentration is reached, the population is considered to be quorate.”18 This causes the binding of the autoinducer to the cognate receptors present within the bacteria. This then further triggers a signal transduction cascade that results in wide-spread changes in the gene expression.19

Types of quorum sensing systems

Gram-negative bacteria: uses 2 proteins which controls the expression of luciferase operon ( luxICDABE) required for light production.

  1. The LuxI -type (auto inducer synthase) -involves in synthesis and emission of acyl homoserine lactone

  2. The LuxR type (cytoplasmic autoinducer receptor)- binds to received acyl homoserine lactone.20 21

After production, the AHL freely diffuses inner and outer membrane of the cell and increases its concentration in response to increasing cell density.22 When the signal reaches a critical, threshold concentration, it is bound by LuxR and this complex activates transcription of the operon encoding luciferase.23 LuxR - AHL complex also acts as positive feedback activator, leading to high expression of luxI gene and production of LuxI protein. This regulation induces the environment with the signal production and produce light.24 A large number of other gram-negative proteobacteria possess LuxIR-type proteins and communicate with AHL signals.25 These systems are used predominantly for intra-species communication as extreme specificity exists between the LuxR proteins and their cognate AHL signals.21 The following figure shows the cell density dependent action of AHL.

Gram-positive bacteria use oligopeptides processed from precursors as autoinducers. These are auto inducing peptides:26 Gram-positive bacteria use two processes in quorum sensing.20 They are:

  1. A two component signal transduction system

  2. Internalization

Why there is a need for eradicating the quorum sensing process

Biofilms are more resilient to mechanical removal and to killing by the host immune system because the matrix within the biofilm protects bacteria from exposure to innate immune defenses and antibiotic treatments.27 Hence, a new era of therapeutics have evolved which turned into a promising potential tool for abolition of infectious diseases caused by bacteria. Thus, Quorum sensing plays a key role in pathogenesis of disease causing by bacteria with its influence at the genetic level leading to regulation of various factors involved in the process.

Mode of Eradicating

Several ways are there for disrupting the quorum sensing as quorum sensing forms the basis of infection. Following ways are enlisted below:

  1. Early colonizers are responsible for creating the pathogenic state. The Presence of Periodontal Pathogens in dental plaque could modulate the virulence properties of S.mutans By Interfering with Its Com Quorum Sensing System. Since The Com Quorum Sensing System Exists In Many Species of Earlier Dental Plaque Colonizers. This Interference of Quorum Sensing By Periodontal Pathogens Such As P.gingivalis and T. denticola Could, At Least In Part, Be A Mechanism of Bacterial Antagonism In Periodontal Diseases.1

  2. Quorum quenchers – synthetic and naturally occurring compounds.

Quorum quenchers-action of magic bullets

Prevention and control of bacterial infection by quorum quenching, which is an antipathogenic or signal interference of quorum sensing has been explored.28 It retards the action of quorum sensing by enzymatic hydrolysis of AHL autoinducers. Quorum sensing blockage are at different site.

  1. QQ by small quorum-sensing inhibitors (QSI).

  2. QQ by AHL- lactonase.

  3. QQ by AHL- acylase.

  4. QQ by paraoxonase enzymes24

Natural quorum sensing inhibitors


Anti QS agents were first characterized in the marine red alga, Delsia puchra. Halogenated furanones produced by Delsia puchra could inhibit QS in a number of bacteria.


Patulin and penicillic acid produced by Penicillium coprobium and P. radicicola, respectively, as inhibitors of quorum sensing in P. aeruginosa. These two compounds target the Las R and Rh1R QS regulators 29


A venom alkaloid from the fire ant Solenopis invicta, solenopsin A - inhibits quorum sensing in P. aeruginosa30

Honey had QSI activity against Erwinia carotovora, Yersinia enterocolitica, Aeromonas hydrophilia 31 (Table 2)

Synthetic quorum sensing inhibitors

There are basically three ways to block QS by developing on the AHL scaffold 24

  1. Introduction of substitutions in the acyl side chain without any change in the lactone ring.

  2. Introduction of substitutions and alterations in the lactone ring with unchanged acyl side chain.

  3. Extensive modifications in both the acyl side chain and the lactone ring.

The synthetic drugs which act as quorum sensing inhibitors are Macrolides, RNA III- related compounds, Halogenated furanones, Homoserine lactone analogue - Antagonism of Homoserine lactone activity and can be prepared as homoserine lactone vaccine.32


The biofilm formation can be disrupted by the naturally occurring quorum sensing inhibitors which plays pivotal as quorum quenchers in inhibiting formation of dental plaque and further progression of periodontal disease. The discovery and further research of cell signaling among microbes results as a new milestone in eradication polymicrobial disease.


Several studies are being done on the benefits of a quorum sensing inhibition. Understanding the extent and significance of bacterial intercellular communication is still in its early stages and more discoveries are required to know the real extent and significance of bacterial cell–cell communication in the environment. Phytochemical quorum sensing inhibitor compounds may serve as a panacea in dentistry. Further research should be carried out to study the ability of quorum quenchers.

Source of funding


Acknowledgment and conflict of interest




B Y Wang P Alvarez J Hong HK Kuramitsu Periodontal pathogens interfere with quorum-sensing-dependent virulence properties in Streptococcus mutansJ Periodontal Res2011461105110


A D Haffajee S S Socransky Microbial etiological agents of destructive periodontal diseasesPeriodontal1994578111


P E Kolenbrander R J Palmer S Periswamy NS Jakubovics Oral multispecies biofilm development and the key role of cell-cell distanceNat Rev Microbial201087471480


H C Flemming J Wingender The biofilm matrixNat Rev20109623633


Barnes M T Aaron Ballering S Katie Leibman S Rachel Wells L.Carol Dunny M Gary Enterococcus faecalis produces abundant extracellular structures containing DNA in the absence of cell lysis during early biofilm formation201210.1128/mBio.00193-12 24


A P Roberts P Mullay Oral Biofilms: a reservoir of transferable, bacterial, antimicrobial resistanceExpert Rev Anti Infect Ther201081214411450


A K Bhardwaj K Vinothkumar N Rajpara Bacterial quorum sensing inhibitors: attractive alternatives for control of infectious pathogens showing multiple drug resistanceRecent Pat Antiinfect Drug Discov2013816883


8. Michael J.Federle and Bonnie L . Bassler Interspecies communication in bacteriaInvest. J.Clin200311212911299


A Mahajan B Singh D Kashyap A Kumar P Mahajan Interspecies Communication and Periodontal DiseaseScientific World Journal2013765434765434


Biradar Baswaraj Prapulla Quorum Sensing in Plaque Biofilms: Challenges and Future ProspectsDev2011100241080


M G Surette M B Miller B L Bassler Quorum sensing in Escherichia coli, Salmonella typhimurium, and Vibrio harveyi: A new family of genes responsible for autoinducer productionProc Natl Acad Sci199996416391644


L Zhou H Zheng Y Tang Q Gong Eugenol inhibits quorum sensing at sub-inhibitory concentrationsBiotechnol Lett20133631637


Y Aparna J Sarada Quorum Quenchers - Past, Present and Future of This Novel TherapeuticsWjpls201513108128


C L Koh C K Sam W F Yin Plant-derived natural products as sources of anti-quorum sensing compoundsSensors2013136217136228


A B Esterela W R Abraham Combining biofilm-controlling compounds and antibiotics as a promising new way to control biofilm infectionsPharmaceuticals2010313741393


K H Nealson J W Hastings Bacterial Bioluminescence: Its Control and Ecological Significance. Microbiological Reviews1979434496518


BL Bassler Opin Curr How bacteria talk to each other: Regulation of gene expression by quorum sensingMicrobiol19992582587


A Suchetha Jayachandran Chitra B M Darshan N Sapna S M Apoorva Chandran Nanditha Quorum sensing - Meetings in the Microbial WorldJ Res Med Den Sci201533161165


EA 15.Meighen J Lederberg Encyclopedia of MicrobiologyAcademic Press1992309311


B Kamalesh Siddharth Sonwane Indra Guptha R K Swetha Quorum Sensing Inhibition, Relevance to PeriodonticsJ Int Oral Health2015716769


Waters M Christopher Bassler L Bonnie Annu Quorum Sensing: Cell-to-Cell Communication in BacteriaRev Cell Dev Biol200521319346


B Heidi Kaplan Greenberg E.P Diffusion of Autoinducer is involved in regulation of the Vibrio fischeri Luminescence SystemJournal of Bacteriology198512101214


A M Stevens K M Dolan E P Greenberg Synergistic binding of the Vibrio fischeri LuxR transcriptional activator domain and RNA polymerase to the lux promoter regionProc Natl Acad Sci1994911261912623


K H Nealson J W Hastings Bacterial bioluminescence: Its control and ecological significanceMicrobiol Rev197943496518


S L Turner Quorum sensing in context: out of molecular biology and into microbial ecologyMicrobiology200237623764Pt. 12


CD Sifri Healthcare epidemiology: quorum sensing: bacteria talk senseClin Infect Dis200847810701076Sifri CD


J G Leid C J Willson M E Shirtliff D J Hassett M R Parsek A K Jeffers The exopolysaccharide alginate protects Pseudomonas aeruginosa biofilm bacteria from IFN-Y-mediated macrophage killingJ Immunol2005751175127520


Y H Dong L H Wang J L Xu H B Zhang X F Zhang L H Zhang Quenching quorum-sensing-dependent bacterial infection by an N-acyl hemoserine lactonaseNature20014116839813817


T B Rasmussen T Bijarnsholt M E Skindersoe M Hentzer P Kristoffersen M Kote Screening for quorum-sensing inhibitors (QSI) by use of a novel genetic system, the QSI selectorJ Bacteriol2005187517991814


C Kim J Kim H Y Park H J Park J H Lee C K Kim Furanone derivatives as quorum-sensing antagonists of Pseudomonas aeruginosaAppl Microbial Biotechnol20088013747


P Truchado A Gil F.A. Tomas Barberan A Allende Inhibition by chestnut honey of N-acyl-l-homoserine lactones and biofilm formation in Erwinia carotovora, Yersinia enterocolitica and Aeromonas hydrophiliaJournal Agricultural and Food Chemistry20095723111861193


T B Rasmussen M Givskov Quorum sensing inhibitors: a bargain of effectsMicrobiology2006152895904


© 2020 Published by Innovative Publication. This is an open access article under the CC BY-NC-ND license (