Semantics of Quorum Sensing
and Quorum Quenching
Saima Naureen
07-arid-1191
Ph.D Zoology
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Contents
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Introduction
Signalling molecules
Mechanism
Quorum Quenching
Biofilms
Applications
Advantages
Conclusion and Future perspective
References
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Introduction. Quorum Sensing
 Cell to cell conversation
 A signaling mechanism
microorganisms
 Control gene expression
 Cell density dependent
in
Example:
• Bacteria and some social insects
(ants and honey bees etc.)
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History
 Research into AHL based quorum sensing started in the late 1960s.
 The marine bioluminescent bacteria Vibrio fischeri was being
grown in liquid cultures and produced light only when large
numbers of bacteria were present (Greenberg, 1967).
 culture media contained an inhibitor of luminescence, which was
removed by the bacteria when large numbers were present
(Kempner & Hanson, 1968).
 It was later shown that the luminescence was initiated by the
accumulation of an activator molecule or "autoinducer" (Nealson et
al, 1970, Eberhard, 1972).
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Cont….
 Vibrio fischeri, lives as a
mutualistic symbiont in the
photophore (or light-producing
organ) of the Hawaiian bobtail
squid.
 free-living (or planktonic) the
autoinducer is at low conc., so
no luminesence.
 highly concentrated in the
photophore
(about
1011
cells/ml)
transcription
of
luciferase is induced, leading
to bioluminescence.
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Decision Making Process
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
(b) a standard response once a threshold number of components is
detected.
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Why do bacteria talk to each other?
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Where Quorum sensing occurs?
 Within and between
bacterial species
 Between prokaryotes and
their eukaryotic host
 Animal
 Plant
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Cross Talk
Cross talk
Interspecies communication
Cross talk has implications in many areas of microbiology
 Antibiotic resistance
 Virulence
 Biofilms (mixed species populations)
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Signaling Molecules
Three types of molecules:
 Oligopeptides Autoincduer (AIPs)
 Acyl-homoserine lactones (AHLs)
 Autoinducer-2 (AI-2)
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Table: 1.1
Class
Signaling Molecules
Strains
Gram- Bacteria
AHLs
V. fisheri
V. harveyi
Gram + Bacteria
AIPs
B.subtilis,
S. aureuas
Gram + Bacteria and
Gram -Bacteria
Al-2
E. coli
V. harveyi
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Oligopeptide Autoinducer
 These are small peptides.
 Regulates competence and sporulation gene expressions
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Mechanism of Oligopeptide Autoinducers
 The precursor peptide is modified, processed and an ATP-binding
cassette (ABC) exporter complex secretes the mature
Oligopeptides-autoinducer.
 At high cell density the autoinducer is detected by a twocomponent signal transduction system. Specifically, the sensor
kinase protein recognizes the autoinducer and subsequently
autophosphorylates at a conserved histidine residue (H).
 The phosphoryl group is transferred to a cognate response
regulator protein, and this protein is phosphorylated on a
conserved aspartate residue (D).
 The phosphorylated response regulator binds to specific target
promoters to modulate the expression of quorum sensing regulated
genes.
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Mechanism of AIPs
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Acyl-homoserine lactones (AHLs)
 These are of several types depending on their length of acyl side
chain.
 Able to diffuse through membrane.
 Involve virulence and biofilm formation.
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Mechanism of Acylhomoserine Lactones AI-1
 These are synthesized by an autoinducer synthase LuxI and
recognized by a autoinducer receptor/DNA binding
transcriptional activator protein LuxR.
 LuxR binds to the promoter region and initiate transcription of
target gene.
 There is a low likelihood of a bacterium detecting its own
secreted inducer
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Mechanism of AHLs
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Autoinducer-2 (AI-2)
 Involve in interspecies communication among bacteria
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Mechanism of Autoinducer-2
 Al-2 are synthesized by LuxS and sensed by Lsr transporter
cassette (ACDB), then phosphoryrated by kinase LsrK.
 The Phospho-Al-2 binds with LsrR and transcription of the lsr
genes is initiated result in (lsrACBDFG) expression
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Mechanism of Al-2
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Hybrid Quorum Sensing Circuit
The hybrid quorum sensing circuit of V. harveyi.
Elements characteristic of both Gram-negative and Gram-positive
bacterial quorum sensing systems are combined to make up the V.
harveyi circuit.
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Mechanism of Hybrid Quorum Sensing
Circuit
 An acyl-HSL autoinducer (AI-1, green pentagons) is produced by
the activity of LuxLM.
 A second autoinducer (AI-2, red pentagons) is synthesized by the
enzyme LuxS. AI-2 is proposed to be a furanone.
 Both autoinducers accumulate as a function of cell density.
 The sensor for AI-1 is LuxN and two proteins, LuxP and LuxQ
function together to detect AI-2.
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Cont…
 LuxN and LuxQ are hybrid sensor kinase/regulator protein that
transduce information to a shared integrator protein called LuxU.
 Lux U send the signal to the response regulator protein LuxO.
 LuxO controls the transcription of a putative repressor protein
(denoted X) and a transcriptional activator protein called LuxR is
also required for expression of the luciferase structure operon (lux
CDABE).
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Mechanism of hybrid quorum sensing
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Quorum Quenching
1.Bacterial Virulence:
QSI is a potential method for inhibition of bacterial
virulence both
 In-vitro
 In-vivo
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Cont…
• 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.
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2. Anti-biotic resistance
Now a days most of bacteria are antibiotic resistant
Penicillin resistant bacteria developed in 1942, just after 2
years of its introduction
Antibiotic sensitive bacteria
Antibiotic resistant bacteria
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Strategies for quorum sensing inhibition
3 strategies can be applied
Targeting signal
Generation
Signal precursor
Targeting AHL signal
dissemination
Signal
Signal
Signal receptor
Signal receptor
Targeting the signal
Receptor
Signal
Signal receptor
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Conversation between bacteria
To Talk? Or Not To Talk?
Quorum sensing
Quorum Quenching
QS Inhibitors
Autoinducers
Regulate QS-controlled
phenotypes
Natural
QSI QSI
Synthetic
QSI
AHL
degradation
system
Block Quorum Sensing Pathway
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Applications
QS research has many potential applications:
 Models to understand biology of sociality
 Understanding bacteria
 To develop new medicines to treat devastating
bacterial infection like
 Cystic fibrosis
 Otitis Media
 Bacteria Endocarditis etc.
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Biofilms
 Bacteria use quorum sensing in biofilm
formation.
 A structured community of bacterial
cells enclosed in self-produced
polymeric matrix.
 They are protective mode of growth
that allows survival in hostile
environment.
 Bacteria in the biofilms are inherently
resistant to killing.
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Why research on Biofilms?
Due to morphology of
biofilms, bacteria capable
of forming them are
highly resistant to
Antibiotics, making
treatment difficult.
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Advantages of Anti-Quorum Sensing
 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.
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Cont…
Next to the potential antimicrobial functionality, quorumsensing molecules, especially the peptides, are investigated for their
use in other therapeutic domains as well, including immunology and
oncology.
This hypothesis is based on
(1) the recent evidence of prokaryote–eukaryote signaling by the use
of quorum-sensing signaling molecules
(2) the apoptotic phenomenon seen in bacteria
(3) the clear similarities between the bacterial quorum-sensing
mechanisms and the metastatic process tumor cells initiate
(4) the multiple receptor targeting and
(5) the possibility of pharmacologic manipulation of peptides,
resulting in increased receptor targeting.
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Conclusions and future perspectives
 QS inhibitors have provided evidence of alternative method for
fighting bacterial infections.
 QS inhibitors can be isolated from the huge natural pool of
chemicals.
 unsuitable compounds lead to lack in selection of human
compatible QS inhibitors.
 Further studies are needed on QS gene expression
 QS inhibitors, may replace the antibiotics.
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Abbreviations
•
•
•
•
•
•
DPD: (4,5-dihydroxy-2,3-pentanedione)
ABC: (ATP binding cassette)
AI: Autoinducing protein
AHLs: N-acylhomoserine lactones
H: Histidine
D: Aspartate
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References
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Smith, D., Wang, J. H., Swatton, J. E., Davenport, P., Price, B., Mikkelsen, H.,
Stickland, H., Nishikawa, K., Gardiol, N. & other authors (2006). Variations on a
theme: diverse N-acyl homoserine lactone-mediated quorum sensing mechanisms in
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http://www.sciencedaily.com
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