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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 of molecules :

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 sensor histidine kinases as receptors.

Signaling is mediated by a phosphorylation cascade that influences the activity of aDNA-binding transcription alregulatory protein termed a response regulator.

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 strategies are not bactericidal and the occurrence of bacterial resistance there fore could be reduced.

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Like wise, approaches aimed at promoting bene ficia lquorum sensing associations may enhance industrial scale production of natural or engineered bacterial products.