Quorum sensing

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QUORUM SENSING
 Bacteria exhibit complex cooperative behaviours, such as conjugal plasmid
transfer, biofilm maturation and virulence.
 Many of these behaviors are regulated by aprocess known as quorum
sensing.
 Each individual bacterium is capable of producing a signaling molecule
(inducer) and each bacterium also has a receptor for the inducer.
 When the inducer binds to the receptor, it activates the transcription of
certain genes, including those responsible for the synthesis of the inducer
itself.
 Imagine that only a few bacteria of the same kind are near by…..
 Diffusion reduces the concentration of the inducer in the surrounding
medium to a negligible amount , so each bacterium produces a very small
amount of the inducer.

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 When concentration of these signaling molecules exceed a particular
threshold value, these molecules are internalized in the cell and activate
particular set of genes in all bacterial population, such as genes responsible
for virulence, competence, stationary phase etc.
 Quorum sensing thus enables bacteria to co-ordinate and respond quickly to
environmental changes, such as the availability of nutrients, other microbes
or toxins in their environment.
QORUM SENSING MOLECULES
Three types ofmolecules:
1) Acyl-homoserine lactones (AHLs)
2) Autoinducer peptides (AIPs)
3) Autoinducer-2 (AI-2)
SIGNAL MOLECULES INVOLVEDIN QUORUM SENSING

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AUTO INDUCE RPEPTIDES
 These are small peptides,regulate gene expression in Gram-positive bacteria
such as Bacillus subtilis,Staphylococcus aureus etc.
 Recognized by membrane bound histidine kinase as receptor.
 Regulates competence and sporulating gene expressions.
AUTOINDUCER-2 (AI-2)
 Involve in interspecies communication among bacteria.
 Present in both Gram (+) and Gram (-) bacteria.
 Chemically these are furanosylborate diester.
Gram negative bacteria
 Quoru sensing was originally discovered in the luminescent bacteriumVibrio
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
large numbers of Bacteria were present.

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 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.
 When a V.fischeri cell is alone, the autoinducer(3-oxo-C6-HSL,anAHL)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 enzy meluciferase,
leading to bioluminescence.
 On reflection,this system is clearly a sensible one. A single cell is not
capable of producing enough luciferase to cause visible luminescence.
 Using quorum sensing, 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 be have differently in the free-living and symbiotic states.
 The pathogen Pseudomonas aeruginosa use squorum sensing to coordinate
behaviors such as biofilm formation, swarming motility, and aggregation.
 These bacteria grow inside a host organism without harming it, until they
reach a threshold concentration.
 Then, having detected that their number is sufficient to over come the host’s
immune system, they become aggressive and form a biofilm, causing
disease.
 This pathogen uses AHL-mediated quorum sensing to regulate the
production of many factors needed for virulence.

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Gram-positive bacteria
 They communicate using modified oligopeptides as signals and “two
component”-type membrane-bound sensorhistidine kinases as receptors.
 Signaling is mediated by a phosphorylation cascade that influences the
activity of aDNA-binding transcription alregulatory protein termed a
responseregulator.
 Each Gram-positive bacterium uses a signal different from that used by other
bacteria and the cognate receptors are exquisitely sensitive to the signals’
structures.
 Peptide signals are not diffusible across the membrane, hence signa lrelease
Is mediated by dedicated oligopeptide exporters.
 It is known that most peptide quorum-sensing signals are cleaved from
larger precursor peptides, which then are modified to contain lactone and
thiolactone rings, lanthionines, and isoprenyl groups .
 S.aureus use sabiphasic strategy to cause disease:
 At low cell density, the bacteria express protein factors that
promote attachment and colonization,

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 Where as at high cell density, the bacteria repress these traits and
initiate secretion of toxins and proteases that are presumably
required for dissemination
 The system consists of an autoinducing peptide of Staphylococcu
saureus (AIP) encoded by agrD and at wo-component sensor
kinase-response regulator pair, AgrC and AgrA, respectively.
 Activated AgrA induces expression of the agrBDCA. Results in
increased AIP levels, which ensures that the entire population
switches from the low-cell- density to the high-cell-density

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INHIBITION OF QUORUM SENSING
 Inhibition of quorum sensing has been proved to be very potent method for
bacterial virulence inhibition.
 Several QS inhibitors molecules has been discovered.
 QS inhibitors have been synthesized and have been isolated from several
Natural extracts such as garlic extract.
 QS inhibitors have shown to be potent virulence inhibitor both in in-vitro
and in-vivo, using infection animal models.
QUORUM QUENCHING
 The ability to disrupt quorum sensing may give one bacterial species an
advantage over an other that relies on quorum sensing.
 Like wise, a host’s ability to interfere with bacterial cell-cell communication
may be crucial in preventing colonization by pathogenic bacteria that use
quorum sensing to coordinate virulence.
 Thus, mechanisms that have evolved to interfere with bacterial cell-cell
communication in processes termed quorum quenching.
Biotechnological Applications of Quorum Quenching
 Naturally occurring quorum-quenching processes are being tested as novel
antimicrobial the rapies. Over expression of aiiA in tobacco and potato
plants confers resistance to E.carotovora, which requires AHL-controlled
virulence factor expression to cause disease.
 Like wise, co culture of Bacillus thuringiensis decreased E.carotovora–
mediated plant disease in an aiiA-dependent manner.
 Mice treated with synthetic antagonists of S.aureus AIPs how resistance to
infection.
 Similarly, purified halogenated furanones appear to attenuate virulence of
bacteria in mouse models.
 These and other examples predict that inhibition of quorum sensing which
offers an attractive alternative to traditional antibiotics because these

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strategies are not bactericidal and the occurrence of bacterial resistance there
fore could be reduced.
 Like wise, approaches aimed at promoting bene ficia lquorum sensing
associations may enhance industrial scale production of natural or
engineered bacterial products.